Next Issue
Volume 13, January
Previous Issue
Volume 12, November
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
6.9
5.4
Journals
Pharmaceutics
Volume 12
Issue 12
share announcement

Pharmaceutics, Volume 12, Issue 12 (December 2020) – 117 articles

Cover Story (view full-size image): The BBB has long been the greatest obstacle to effective pharmaceutical treatment of brain tumors. Disruption and increased permeability of the BBB in and around brain tumors is heterogeneous and unpredictable, and this disruption does not allow for effective delivery of oncology drugs on their own. As a result, a wide variety of novel formulation and delivery strategies have been explored to overcome this obstacle. These include invasive strategies such as CED and polymeric wafers which bypass the BBB, as well as noninvasive BBB-disruption strategies, nanoparticle formulations, and receptor-mediated delivery. The vast variety of approaches speaks to the imperative need and difficulty of solving one of the great puzzles of modern oncology. View this paper.
  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Reader to open them.
Order results
Result details
Section
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
26 pages, 5761 KiB  
Review
Nuclear Medicine in Times of COVID-19: How Radiopharmaceuticals Could Help to Fight the Current and Future Pandemics
by Felix Neumaier, Boris D. Zlatopolskiy and Bernd Neumaier
Pharmaceutics 2020, 12(12), 1247; https://doi.org/10.3390/pharmaceutics12121247 - 21 Dec 2020
Cited by 8 | Viewed by 3499
Abstract
The emergence and global spread of COVID-19, an infectious disease caused by the novel coronavirus SARS-CoV-2, has resulted in a continuing pandemic threat to global health. Nuclear medicine techniques can be used for functional imaging of (patho)physiological processes at the cellular or molecular [...] Read more.
The emergence and global spread of COVID-19, an infectious disease caused by the novel coronavirus SARS-CoV-2, has resulted in a continuing pandemic threat to global health. Nuclear medicine techniques can be used for functional imaging of (patho)physiological processes at the cellular or molecular level and for treatment approaches based on targeted delivery of therapeutic radionuclides. Ongoing development of radiolabeling methods has significantly improved the accessibility of radiopharmaceuticals for in vivo molecular imaging or targeted radionuclide therapy, but their use for biosafety threats such as SARS-CoV-2 is restricted by the contagious nature of these agents. Here, we highlight several potential uses of nuclear medicine in the context of SARS-CoV-2 and COVID-19, many of which could also be performed in laboratories without dedicated containment measures. In addition, we provide a broad overview of experimental or repurposed SARS-CoV-2-targeting drugs and describe how radiolabeled analogs of these compounds could facilitate antiviral drug development and translation to the clinic, reduce the incidence of late-stage failures and possibly provide the basis for radionuclide-based treatment strategies. Based on the continuing threat by emerging coronaviruses and other pathogens, it is anticipated that these applications of nuclear medicine will become a more important part of future antiviral drug development and treatment. Full article
►▼ Show Figures

Figure 1

21 pages, 2112 KiB  
Review
Nose-to-Brain Delivery of Antioxidants as a Potential Tool for the Therapy of Neurological Diseases
by Maria Cristina Bonferoni, Giovanna Rassu, Elisabetta Gavini, Milena Sorrenti, Laura Catenacci and Paolo Giunchedi
Pharmaceutics 2020, 12(12), 1246; https://doi.org/10.3390/pharmaceutics12121246 - 21 Dec 2020
Cited by 16 | Viewed by 3246
Abstract
Oxidative stress has a key role in the pathogenesis of neurodegenerative disorders such as Alzheimer’s, Parkinson’s, and Huntington’s diseases and can be an important cause of the damages in cerebral ischemia. Oxidative stress arises from high levels of reactive oxygen species (ROS). Consequently, [...] Read more.
Oxidative stress has a key role in the pathogenesis of neurodegenerative disorders such as Alzheimer’s, Parkinson’s, and Huntington’s diseases and can be an important cause of the damages in cerebral ischemia. Oxidative stress arises from high levels of reactive oxygen species (ROS). Consequently, on this rational base, antioxidants (many of natural origin) are proposed as potential drugs to prevent ROS noxious actions because they can protect the target tissues from the oxidative stress. However, the potential of antioxidants is limited, owing to the presence of the blood–brain barrier (BBB), which is difficult to cross with a consequent low bioavailability of the drug into the brain after systemic (intravenous, intraperitoneal, oral) administrations. One strategy to improve the delivery of antioxidants to the brain involves the use of the so-called nose-to-brain route, with the administration of the antioxidant in specific nasal formulations and its passage to the central nervous system (CNS) mainly through the olfactory nerve way. In the current literature, many examples show encouraging results in studies carried out in cell cultures and in animal models about the potential neuroprotective effects of antioxidants when administered through the nose. This review concerns the nose-to-brain route for the brain targeting of antioxidants as a potential tool for the therapy of neurological diseases. Full article
(This article belongs to the Special Issue Nose to Brain Delivery (Volume II))
►▼ Show Figures

Figure 1

18 pages, 4371 KiB  
Article
Aqueous Extracts of Morus alba Root Bark and Cornus officinalis Fruit Protect against Osteoarthritis Symptoms in Testosterone-Deficient and Osteoarthritis-Induced Rats
by Sunmin Park, Bo Reum Moon, Ji Eun Kim, Hyun Joo Kim and Ting Zhang
Pharmaceutics 2020, 12(12), 1245; https://doi.org/10.3390/pharmaceutics12121245 - 21 Dec 2020
Cited by 10 | Viewed by 2893
Abstract
Water extracts of both Morus alba L. root bark (MBW) and Cornus officinalis Siebold and Zucc fruit (CFW) have traditionally been used to promote men’s health in the elderly in Asia. We determined that the 12-week consumption of MBW and CFW could alleviate [...] Read more.
Water extracts of both Morus alba L. root bark (MBW) and Cornus officinalis Siebold and Zucc fruit (CFW) have traditionally been used to promote men’s health in the elderly in Asia. We determined that the 12-week consumption of MBW and CFW could alleviate testosterone-deficiency syndrome and osteoarthritis (OA) symptoms in testosterone-deficient rats, and the action mechanisms were explored. Rats with bilateral orchiectomy (ORX) were fed a 45% fat diet containing either 0.5% MBW (ORX-MBW), 0.5% CFW(ORX-CFW), or 0.5% dextrin (ORX-CON). Sham-operated rats also received 0.5% dextrin (Non-ORX-CON). After 8 weeks of treatment, all rats had an injection of monoiodoacetate (MIA) into the left knee, and they continued the same diet for the additional 4 weeks. ORX-CFW and ORX-MBW partially prevented the reduction of serum testosterone concentrations and decreased insulin resistance, compared to the ORX-CON. ORX-CFW and ORX-MBW protected against the reduction of bone mineral density (BMD) and lean body mass (LBM) compared to the ORX-CON. The limping and edema scores were lower in the order of the ORX-CON, ORX-CRF = ORX-MBW, and Non-ORX-CON (p < 0.05). The scores for pain behaviors, measured by weight-distribution on the OA leg and maximum running velocity on a treadmill, significantly decreased in the same order as limping scores. ORX-MBW protected against the increased expression of matrix metalloproteinase (MMP)-3 and MMP-13 and reduced the production of inflammatory markers such as TNF-α and IL-1β, by MIA in the articular cartilage, compared to the ORX-CON (p < 0.05). The cartilage damage near the tidemark of the knee and proteoglycan loss was significantly less in ORX-MBW than ORX-CON. In conclusion, MBW, possibly CFW, could be effective alternative therapeutic agents for preventing osteoarthritis in testosterone-deficient elderly men. Full article
►▼ Show Figures

Graphical abstract

17 pages, 2394 KiB  
Article
Effect of Plant Extracts on the Characteristics of Silver Nanoparticles for Topical Application
by Ioanna K. Siakavella, Fotini Lamari, Dimitrios Papoulis, Malvina Orkoula, Patroula Gkolfi, Michail Lykouras, Konstantinos Avgoustakis and Sophia Hatziantoniou
Pharmaceutics 2020, 12(12), 1244; https://doi.org/10.3390/pharmaceutics12121244 - 21 Dec 2020
Cited by 34 | Viewed by 3529
Abstract
Silver nanoparticles (AgNPs) were synthesized using hydroalcoholic extracts of dittany (Origanum dictamnus), sage (Salvia officinalis), sea buckthorn (Elaeagnus rhamnoides, syn. Hippophae rhamnoides), and calendula (Calendula officinalis) as reducing agents. AgNPs synthesized using NaBH4 [...] Read more.
Silver nanoparticles (AgNPs) were synthesized using hydroalcoholic extracts of dittany (Origanum dictamnus), sage (Salvia officinalis), sea buckthorn (Elaeagnus rhamnoides, syn. Hippophae rhamnoides), and calendula (Calendula officinalis) as reducing agents. AgNPs synthesized using NaBH4 and citric acid were used as control. The impact of the origin of the extract and preparation conditions (light, temperature, reaction time) on the properties of the synthesized AgNPs was investigated. The structure, morphology, composition, physicochemical characteristics, and colloidal stability were characterized using dynamic laser scattering (DLS), ultraviolet-visible spectrophotometry (UV–/Vis), XRD, X-ray fluorescence (XRF), TEM, and FTΙR. The reduction of total phenolic and flavonoid content of the extracts after the reaction of AgNPs synthesis was also determined. Low IC50 values for all types of AgNPs revealed good antioxidant activity, attributable to the phenolic and flavonoid content of their surface. The results suggest that plant extract selection is important to the green synthesis of AgNPs because it affects the kinetics of their synthesis as well as their morphology, physicochemical characteristics, and colloidal stability. In vitro permeation studies on porcine skin revealed that AgNPs remained at the upper layers of stratum corneum and did not penetrate the skin barrier after 4 h of cutaneous application suggesting the safety of their application on intact skin for a relatively short time. Full article
(This article belongs to the Collection Women in Pharmaceutics)
►▼ Show Figures

Graphical abstract

18 pages, 3760 KiB  
Review
Combining Chemistry and Engineering for Hepatocellular Carcinoma: Nano-Scale and Smaller Therapies
by Danielle L. Stolley, Anna Colleen Crouch, Aliçan Özkan, Erin H. Seeley, Elizabeth M. Whitley, Marissa Nichole Rylander and Erik N. K. Cressman
Pharmaceutics 2020, 12(12), 1243; https://doi.org/10.3390/pharmaceutics12121243 - 20 Dec 2020
Cited by 6 | Viewed by 2951
Abstract
Primary liver cancer, or hepatocellular carcinoma (HCC), is a major worldwide cause of death from carcinoma. Most patients are not candidates for surgery and medical therapies, including new immunotherapies, have not shown major improvements since the modest benefit seen with the introduction of [...] Read more.
Primary liver cancer, or hepatocellular carcinoma (HCC), is a major worldwide cause of death from carcinoma. Most patients are not candidates for surgery and medical therapies, including new immunotherapies, have not shown major improvements since the modest benefit seen with the introduction of sorafenib over a decade ago. Locoregional therapies for intermediate stage disease are not curative but provide some benefit. However, upon close scrutiny, there is still residual disease in most cases. We review the current status for treatment of intermediate stage disease, summarize the literature on correlative histopathology, and discuss emerging methods at micro-, nano-, and pico-scales to improve therapy. These include transarterial hyperthermia methods and thermoembolization, along with microfluidics model systems and new applications of mass spectrometry imaging for label-free analysis of pharmacokinetics and pharmacodynamics. Full article
(This article belongs to the Special Issue Nanopharmaceuticals for Image-Guided Cancer Therapy and Diagnosis)
►▼ Show Figures

Graphical abstract

15 pages, 2243 KiB  
Article
Structure-to-Efficacy Relationship of HPMA-Based Nanomedicines: The Tumor Spheroid Penetration Study
by Júlia Kudláčová, Lenka Kotrchová, Libor Kostka, Eva Randárová, Marcela Filipová, Olga Janoušková, Jun Fang and Tomáš Etrych
Pharmaceutics 2020, 12(12), 1242; https://doi.org/10.3390/pharmaceutics12121242 - 20 Dec 2020
Cited by 5 | Viewed by 2228
Abstract
Nanomedicines are a novel class of therapeutics that benefit from the nano dimensions of the drug carrier. These nanosystems are highly advantageous mainly within cancer treatment due to their enhanced tumor accumulation. Monolayer tumor cells frequently used in routine preclinical assessment of nanotherapeutics [...] Read more.
Nanomedicines are a novel class of therapeutics that benefit from the nano dimensions of the drug carrier. These nanosystems are highly advantageous mainly within cancer treatment due to their enhanced tumor accumulation. Monolayer tumor cells frequently used in routine preclinical assessment of nanotherapeutics do not have a spatial structural architecture that allows the investigation of the penetration of nanomedicines to predict their behavior in real tumor tissue. Therefore, tumor spheroids from colon carcinoma C26 cells and glioblastoma U87-MG cells were used as 3D in vitro models to analyze the effect of the inner structure, hydrodynamic size, dispersity, and biodegradability of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-based nanomedicines carrying anticancer drug pirarubicin (THP) on the penetration within spheroids. While almost identical penetration through spheroids of linear and star-like copolymers and also their conjugates with THP was observed, THP penetration after nanomedicines application was considerably deeper than for the free THP, thus proving the benefit of polymer carriers. The cytotoxicity of THP-polymer nanomedicines against tumor cell spheroids was almost identical as for the free THP, whereas the 2D cell cytotoxicity of these nanomedicines is usually lower. The nanomedicines thus proved the enhanced efficacy within the more realistic 3D tumor cell spheroid system. Full article
(This article belongs to the Special Issue Design of Novel Polymeric Systems for Controlled Drug Delivery)
►▼ Show Figures

Graphical abstract

10 pages, 1131 KiB  
Article
An Investigation into the Relationship between Xanthan Gum Film Coating Materials and Predicted Oro-Esophageal Gliding Performance for Solid Oral Dosage Forms
by Nélio Drumond and Sven Stegemann
Pharmaceutics 2020, 12(12), 1241; https://doi.org/10.3390/pharmaceutics12121241 - 20 Dec 2020
Cited by 4 | Viewed by 2581
Abstract
Oral drug therapy is generally provided in the form of solid oral dosage forms (SODF) that have to be swallowed and move throughout the oro-esophageal system. Previous studies have provided evidence that the oro-esophageal transit of SODF depends on their shape, size, density, [...] Read more.
Oral drug therapy is generally provided in the form of solid oral dosage forms (SODF) that have to be swallowed and move throughout the oro-esophageal system. Previous studies have provided evidence that the oro-esophageal transit of SODF depends on their shape, size, density, and surface characteristics. To estimate the impact of SODF surface coatings during esophageal transit, an in vitro system was implemented to investigate the gliding performance across an artificial mucous layer. In this work, formulations comprised of different slippery-inducing agents combined with a common film forming agent were evaluated using the artificial mucous layer system. Xanthan gum (XG) and polyethylene glycol 1500 (PEG) were applied as film-forming agents, while carnauba wax (CW), lecithin (LE), carrageenan (CA), gellan gum (GG) and sodium alginate (SA), and their combination with sodium lauryl sulfate (SLS), were applied as slippery-inducing components. All tested formulations presented lower static friction (SF) as compared to the negative control (uncoated disc, C, F0), whereas only CW/SLS-based formulations showed similar performance to F0 regarding dynamic friction (DF). The applied multivariate analysis approach allowed a higher level of detail to the evaluation and supported a better identification of excipients and respective concentrations that are predicted to improve in vivo swallowing safety. Full article
(This article belongs to the Special Issue Optimisation of Patient Centric Medicines for the Older Population)
►▼ Show Figures

Graphical abstract

23 pages, 1506 KiB  
Review
Pharmacogenetic Testing: A Tool for Personalized Drug Therapy Optimization
by Kristina A. Malsagova, Tatyana V. Butkova, Arthur T. Kopylov, Alexander A. Izotov, Natalia V. Potoldykova, Dmitry V. Enikeev, Vagarshak Grigoryan, Alexander Tarasov, Alexander A. Stepanov and Anna L. Kaysheva
Pharmaceutics 2020, 12(12), 1240; https://doi.org/10.3390/pharmaceutics12121240 - 19 Dec 2020
Cited by 20 | Viewed by 8106
Abstract
Pharmacogenomics is a study of how the genome background is associated with drug resistance and how therapy strategy can be modified for a certain person to achieve benefit. The pharmacogenomics (PGx) testing becomes of great opportunity for physicians to make the proper decision [...] Read more.
Pharmacogenomics is a study of how the genome background is associated with drug resistance and how therapy strategy can be modified for a certain person to achieve benefit. The pharmacogenomics (PGx) testing becomes of great opportunity for physicians to make the proper decision regarding each non-trivial patient that does not respond to therapy. Although pharmacogenomics has become of growing interest to the healthcare market during the past five to ten years the exact mechanisms linking the genetic polymorphisms and observable responses to drug therapy are not always clear. Therefore, the success of PGx testing depends on the physician’s ability to understand the obtained results in a standardized way for each particular patient. The review aims to lead the reader through the general conception of PGx and related issues of PGx testing efficiency, personal data security, and health safety at a current clinical level. Full article
(This article belongs to the Special Issue Precision Medicine: Applied Concepts of Pharmacogenomics in Patients with Various Diseases and Polypharmacy)
►▼ Show Figures

Figure 1

26 pages, 5271 KiB  
Article
3D-Printed Veterinary Dosage Forms—A Comparative Study of Three Semi-Solid Extrusion 3D Printers
by Erica Sjöholm, Rathna Mathiyalagan, Dhayakumar Rajan Prakash, Lisa Lindfors, Qingbo Wang, Xiaoju Wang, Samuli Ojala and Niklas Sandler
Pharmaceutics 2020, 12(12), 1239; https://doi.org/10.3390/pharmaceutics12121239 - 19 Dec 2020
Cited by 28 | Viewed by 4624
Abstract
Currently, the number of approved veterinary medicines are limited, and human medications are used off-label. These approved human medications are of too high potencies for a cat or a small dog breed. Therefore, there is a dire demand for smaller doses of veterinary [...] Read more.
Currently, the number of approved veterinary medicines are limited, and human medications are used off-label. These approved human medications are of too high potencies for a cat or a small dog breed. Therefore, there is a dire demand for smaller doses of veterinary medicines. This study aims to investigate the use of three semi-solid extrusion 3D printers in a pharmacy or animal clinic setting for the extemporaneous manufacturing of prednisolone containing orodispersible films for veterinary use. Orodispersible films with adequate content uniformity and acceptance values as defined by the European Pharmacopoeia were produced with one of the studied printers, namely the Allevi 2 bioprinter. Smooth and flexible films with high mechanical strength, neutral pH, and low moisture content were produced with a high correlation between the prepared design and the obtained drug amount, indicating that the Allevi 2 printer could successfully be used to extemporaneously manufacture personalized doses for animals at the point-of-care. Full article
(This article belongs to the Special Issue Applications of Additive Manufacturing in Pharmaceutics)
►▼ Show Figures

Graphical abstract

12 pages, 1389 KiB  
Article
Solubility, Permeability, and Dissolution Rate of Naftidrofuryl Oxalate Based on BCS Criteria
by Marta Kus-Slowinska, Monika Wrzaskowska, Izabela Ibragimow, Piotr Igor Czaklosz, Anna Olejnik and Hanna Piotrowska-Kempisty
Pharmaceutics 2020, 12(12), 1238; https://doi.org/10.3390/pharmaceutics12121238 - 19 Dec 2020
Cited by 3 | Viewed by 3249
Abstract
The Biopharmaceutics Classification System (BCS) was conceived to classify drug substances by their in vitro aqueous solubility and permeability properties. The essential activity of naftidrofuryl oxalate (NF) has been described as the inhibition of the serotonin receptors (5-HT2), resulting in vasodilation [...] Read more.
The Biopharmaceutics Classification System (BCS) was conceived to classify drug substances by their in vitro aqueous solubility and permeability properties. The essential activity of naftidrofuryl oxalate (NF) has been described as the inhibition of the serotonin receptors (5-HT2), resulting in vasodilation and decreasing blood pressure. Since the early 1980s, NF has been used to treat several venous and cerebral diseases. There is no data available on the BCS classification of NF. However, based on its physical-chemical properties, NF might be considered to belong to the 1st or the 3rd BCS class. The present study aimed to provide data concerning the solubility and permeability of NF through Caco-2 monolayers and propose its preliminary classification into BCS. We showed that NF is a highly soluble and permeable drug substance; thus, it might be suggested to belong to BCS class I. Additionally, a high dissolution rate of the encapsulated NF based on Praxilene® 100 mg formulation was revealed. Hence, it might be considered as an immediate-release (IR). Full article
(This article belongs to the Special Issue Drug Absorption Studies: In Situ, In Vitro and In Silico Models)
►▼ Show Figures

Graphical abstract

17 pages, 2099 KiB  
Article
Applying Microfluidics for the Production of the Cationic Liposome-Based Vaccine Adjuvant CAF09b
by Signe Tandrup Schmidt, Dennis Christensen and Yvonne Perrie
Pharmaceutics 2020, 12(12), 1237; https://doi.org/10.3390/pharmaceutics12121237 - 19 Dec 2020
Cited by 8 | Viewed by 4200
Abstract
Subunit vaccines require particulate adjuvants to induce the desired immune responses. Pre-clinical manufacturing methods of adjuvants are often batch dependent, which complicates scale-up for large-scale good manufacturing practice (GMP) production. The cationic liposomal adjuvant CAF09b, composed of dioctadecyldimethylammonium bromide (DDA), monomycoloyl glycerol analogue [...] Read more.
Subunit vaccines require particulate adjuvants to induce the desired immune responses. Pre-clinical manufacturing methods of adjuvants are often batch dependent, which complicates scale-up for large-scale good manufacturing practice (GMP) production. The cationic liposomal adjuvant CAF09b, composed of dioctadecyldimethylammonium bromide (DDA), monomycoloyl glycerol analogue 1 (MMG) and polyinosinic:polycytidylic acid [poly(I:C)], is currently being clinically evaluated in therapeutic cancer vaccines. Microfluidics is a promising new method for large-scale manufacturing of particle-based medicals, which is scalable from laboratory to GMP production, and a protocol for production of CAF09b by this method was therefore validated. The influence of the manufacture parameters [Ethanol] (20–40% v/v), [Lipid] (DDA and MMG, 6–12 mg/mL) and dimethyl sulfoxide [DMSO] (0–10% v/v) on the resulting particle size, colloidal stability and adsorption of poly(I:C) was evaluated in a design-of-experiments study. [Ethanol] and [DMSO] affected the resulting particle sizes, while [Lipid] and [DMSO] affected the colloidal stability. In all samples, poly(I:C) was encapsulated within the liposomes. At [Ethanol] 30% v/v, most formulations were stable at 21 days of manufacture with particle sizes <100 nm. An in vivo comparison in mice of the immunogenicity to the cervical cancer peptide antigen HPV-16 E7 adjuvanted with CAF09b prepared by lipid film rehydration or microfluidics showed no difference between the formulations, indicating adjuvant activity is intact. Thus, it is possible to prepare suitable formulations of CAF09b by microfluidics. Full article
(This article belongs to the Special Issue Technologies for the Development of Next Generation Adjuvanted Vaccines)
►▼ Show Figures

Figure 1

19 pages, 1839 KiB  
Review
Tight Junction Modulating Bioprobes for Drug Delivery System to the Brain: A Review
by Keisuke Tachibana, Yumi Iwashita, Erika Wakayama, Itsuki Nishino, Taiki Nishikaji and Masuo Kondoh
Pharmaceutics 2020, 12(12), 1236; https://doi.org/10.3390/pharmaceutics12121236 - 19 Dec 2020
Cited by 10 | Viewed by 3418
Abstract
The blood-brain barrier (BBB), which is composed of endothelial cells, pericytes, astrocytes, and neurons, separates the brain extracellular fluid from the circulating blood, and maintains the homeostasis of the central nervous system (CNS). The BBB endothelial cells have well-developed tight junctions (TJs) and [...] Read more.
The blood-brain barrier (BBB), which is composed of endothelial cells, pericytes, astrocytes, and neurons, separates the brain extracellular fluid from the circulating blood, and maintains the homeostasis of the central nervous system (CNS). The BBB endothelial cells have well-developed tight junctions (TJs) and express specific polarized transport systems to tightly control the paracellular movements of solutes, ions, and water. There are two types of TJs: bicellular TJs (bTJs), which is a structure at the contact of two cells, and tricellular TJs (tTJs), which is a structure at the contact of three cells. Claudin-5 and angulin-1 are important components of bTJs and tTJs in the brain, respectively. Here, we review TJ-modulating bioprobes that enable drug delivery to the brain across the BBB, focusing on claudin-5 and angulin-1. Full article
(This article belongs to the Special Issue New Drug Delivery across the Blood–Brain Barrier)
►▼ Show Figures

Figure 1

36 pages, 1457 KiB  
Review
The Phospholipid Research Center: Current Research in Phospholipids and Their Use in Drug Delivery
by Simon Drescher and Peter van Hoogevest
Pharmaceutics 2020, 12(12), 1235; https://doi.org/10.3390/pharmaceutics12121235 - 18 Dec 2020
Cited by 67 | Viewed by 7566
Abstract
This review summarizes the research on phospholipids and their use for drug delivery related to the Phospholipid Research Center Heidelberg (PRC). The focus is on projects that have been approved by the PRC since 2017 and are currently still ongoing or have recently [...] Read more.
This review summarizes the research on phospholipids and their use for drug delivery related to the Phospholipid Research Center Heidelberg (PRC). The focus is on projects that have been approved by the PRC since 2017 and are currently still ongoing or have recently been completed. The different projects cover all facets of phospholipid research, from basic to applied research, including the use of phospholipids in different administration forms such as liposomes, mixed micelles, emulsions, and extrudates, up to industrial application-oriented research. These projects also include all routes of administration, namely parenteral, oral, and topical. With this review we would like to highlight possible future research directions, including a short introduction into the world of phospholipids. Full article
(This article belongs to the Special Issue Recent Advances in the Use of Phospholipids in Drug Delivery)
►▼ Show Figures

Figure 1

14 pages, 2917 KiB  
Article
A Mixture of Tocopherol Acetate and L-Menthol Synergistically Promotes Hair Growth in C57BL/6 Mice
by Seunghyun Ahn, Jung Yeon Lee, Sang Mi Choi, Yujeong Shin and Seyeon Park
Pharmaceutics 2020, 12(12), 1234; https://doi.org/10.3390/pharmaceutics12121234 - 18 Dec 2020
Cited by 8 | Viewed by 4229
Abstract
Oral finasteride and topical minoxidil are single components approved by the US FDA for treating hair loss. Some other compounds originating from natural products are also traditionally used for promoting hair growth. In this study, observations of treated keratinocyte cells were used to [...] Read more.
Oral finasteride and topical minoxidil are single components approved by the US FDA for treating hair loss. Some other compounds originating from natural products are also traditionally used for promoting hair growth. In this study, observations of treated keratinocyte cells were used to demonstrate that tocopherol acetate, L-menthol, and stevioside exert an effect on cell regeneration. Furthermore, these were topically applied to the shaved skin of C57BL/6 mice to observe their effects on hair growth. A mixture of tocopherol acetate, L-menthol, and stevioside showed the highest potential for promoting hair growth in vivo. In in vivo experiments, the mixture of tocopherol acetate, L-menthol, and stevioside was more effective than tocopherol acetate or L-menthol alone in promoting hair growth. The transcriptome analysis of skin from the dorsal side of a mouse treated with tocopherol acetate or L-menthol versus vehicle revealed key changes in keratin, keratin-associated protein, forkhead box, sonic hedgehog, fibroblast growth factor 10, desmoglein 4, deoxyribonuclease 1-like 2, and cadherin 3, known to play roles in promoting hair growth. Full article
►▼ Show Figures

Figure 1

42 pages, 4013 KiB  
Review
Nanovesicle-Mediated Delivery Systems for CRISPR/Cas Genome Editing
by Dongyoon Kim, Quoc-Viet Le, Yina Wu, Jinwon Park and Yu-Kyoung Oh
Pharmaceutics 2020, 12(12), 1233; https://doi.org/10.3390/pharmaceutics12121233 - 18 Dec 2020
Cited by 21 | Viewed by 7134
Abstract
Genome-editing technology has emerged as a potential tool for treating incurable diseases for which few therapeutic modalities are available. In particular, discovery of the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system together with the design of single-guide RNAs (sgRNAs) has sparked medical [...] Read more.
Genome-editing technology has emerged as a potential tool for treating incurable diseases for which few therapeutic modalities are available. In particular, discovery of the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system together with the design of single-guide RNAs (sgRNAs) has sparked medical applications of genome editing. Despite the great promise of the CRISPR/Cas system, its clinical application is limited, in large part, by the lack of adequate delivery technology. To overcome this limitation, researchers have investigated various systems, including viral and nonviral vectors, for delivery of CRISPR/Cas and sgRNA into cells. Among nonviral delivery systems that have been studied are nanovesicles based on lipids, polymers, peptides, and extracellular vesicles. These nanovesicles have been designed to increase the delivery of CRISPR/Cas and sgRNA through endosome escape or using various stimuli such as light, pH, and environmental features. This review covers the latest research trends in nonviral, nanovesicle-based delivery systems that are being applied to genome-editing technology and suggests directions for future progress. Full article
(This article belongs to the Special Issue Nanovesicles for Targeted Drug Delivery)
►▼ Show Figures

Graphical abstract

26 pages, 3656 KiB  
Review
Biodegradable Nanoparticle for Cornea Drug Delivery: Focus Review
by Mohammadmahdi Mobaraki, Madjid Soltani, Samaneh Zare Harofte, Elham L. Zoudani, Roshanak Daliri, Mohamadreza Aghamirsalim and Kaamran Raahemifar
Pharmaceutics 2020, 12(12), 1232; https://doi.org/10.3390/pharmaceutics12121232 - 18 Dec 2020
Cited by 27 | Viewed by 4148
Abstract
During recent decades, researchers all around the world have focused on the characteristic pros and cons of the different drug delivery systems for cornea tissue change for sense organs. The delivery of various drugs for cornea tissue is one of the most attractive [...] Read more.
During recent decades, researchers all around the world have focused on the characteristic pros and cons of the different drug delivery systems for cornea tissue change for sense organs. The delivery of various drugs for cornea tissue is one of the most attractive and challenging activities for researchers in biomaterials, pharmacology, and ophthalmology. This method is so important for cornea wound healing because of the controllable release rate and enhancement in drug bioavailability. It should be noted that the delivery of various kinds of drugs into the different parts of the eye, especially the cornea, is so difficult because of the unique anatomy and various barriers in the eye. Nanoparticles are investigated to improve drug delivery systems for corneal disease. Biodegradable nanocarriers for repeated corneal drug delivery is one of the most attractive and challenging methods for corneal drug delivery because they have shown acceptable ability for this purpose. On the other hand, by using these kinds of nanoparticles, a drug could reside in various part of the cornea for longer. In this review, we summarized all approaches for corneal drug delivery with emphasis on the biodegradable nanoparticles, such as liposomes, dendrimers, polymeric nanoparticles, niosomes, microemulsions, nanosuspensions, and hydrogels. Moreover, we discuss the anatomy of the cornea at first and gene therapy at the end. Full article
(This article belongs to the Special Issue Biodegradable Nanoparticulate Drug Delivery Systems)
►▼ Show Figures

Figure 1

23 pages, 33776 KiB  
Article
Therapeutic Angiogenesis by a “Dynamic Duo”: Simultaneous Expression of HGF and VEGF165 by Novel Bicistronic Plasmid Restores Blood Flow in Ischemic Skeletal Muscle
by Ekaterina Slobodkina, Maria Boldyreva, Maxim Karagyaur, Roman Eremichev, Natalia Alexandrushkina, Vadim Balabanyan, Zhanna Akopyan, Yelena Parfyonova, Vsevolod Tkachuk and Pavel Makarevich
Pharmaceutics 2020, 12(12), 1231; https://doi.org/10.3390/pharmaceutics12121231 - 18 Dec 2020
Cited by 7 | Viewed by 2995
Abstract
Therapeutic angiogenesis is a promising strategy for relief of ischemic conditions, and gene delivery was used to stimulate blood vessels’ formation and growth. We have previously shown that intramuscular injection of a mixture containing plasmids encoding vascular endothelial growth factor (VEGF)165 and hepatocyte [...] Read more.
Therapeutic angiogenesis is a promising strategy for relief of ischemic conditions, and gene delivery was used to stimulate blood vessels’ formation and growth. We have previously shown that intramuscular injection of a mixture containing plasmids encoding vascular endothelial growth factor (VEGF)165 and hepatocyte growth factor (HGF) leads to restoration of blood flow in mouse ischemic limb, and efficacy of combined delivery was superior to each plasmid administered alone. In this work, we evaluated different approaches for co-expression of HGF and VEGF165 genes in a panel of candidate plasmid DNAs (pDNAs) with internal ribosome entry sites (IRESs), a bidirectional promoter or two independent promoters for each gene of interest. Studies in HEK293T culture showed that all plasmids provided synthesis of HGF and VEGF165 proteins and stimulated capillary formation by human umbilical vein endothelial cells (HUVEC), indicating the biological potency of expressed factors. Tests in skeletal muscle explants showed a dramatic difference and most plasmids failed to express HGF and VEGF165 in a significant quantity. However, a bicistronic plasmid with two independent promoters (cytomegalovirus (CMV) for HGF and chicken b-actin (CAG) for VEGF165) provided expression of both grow factors in skeletal muscle at an equimolar ratio. Efficacy tests of bicistronic plasmid were performed in a mouse model of hind limb ischemia. Intramuscular administration of plasmid induced significant restoration of perfusion compared to an empty vector and saline. These findings were supported by increased CD31+ capillary density in animals that received pHGF/VEGF. Overall, our study reports a first-in-class candidate gene therapy drug to deliver two pivotal angiogenic growth factors (HGF and VEGF165) with properties that provide basis for future development of treatment for an unmet medical need—peripheral artery disease and associated limb ischemia. Full article
(This article belongs to the Section Gene and Cell Therapy)
►▼ Show Figures

Figure 1

27 pages, 2252 KiB  
Review
Intranasal Nanoemulsions for Direct Nose-to-Brain Delivery of Actives for CNS Disorders
by Shiv Bahadur, Dinesh M. Pardhi, Jarkko Rautio, Jessica M. Rosenholm and Kamla Pathak
Pharmaceutics 2020, 12(12), 1230; https://doi.org/10.3390/pharmaceutics12121230 - 18 Dec 2020
Cited by 63 | Viewed by 10525
Abstract
The treatment of various central nervous system (CNS) diseases has been challenging, despite the rapid development of several novel treatment approaches. The blood–brain barrier (BBB) is one of the major issues in the treatment of CNS diseases, having major role in the protection [...] Read more.
The treatment of various central nervous system (CNS) diseases has been challenging, despite the rapid development of several novel treatment approaches. The blood–brain barrier (BBB) is one of the major issues in the treatment of CNS diseases, having major role in the protection of the brain but simultaneously constituting the main limiting hurdle for drugs targeting the brain. Nasal drug delivery has gained significant interest for brain targeting over the past decades, wherein the drug is directly delivered to the brain by the trigeminal and olfactory pathway. Various novel and promising formulation approaches have been explored for drug targeting to the brain by nasal administration. Nanoemulsions have the potential to avoid problems, including low solubility, poor bioavailability, slow onset of action, and enzymatic degradation. The present review highlights research scenarios of nanoemulsions for nose-to-brain delivery for the management of CNS ailments classified on the basis of brain disorders and further identifies the areas that remain unexplored. The significance of the total dose delivered to the target region, biodistribution studies, and long-term toxicity studies have been identified as the key areas of future research. Full article
(This article belongs to the Special Issue Development of Micro and Nano Systems for the Drug Delivery)
►▼ Show Figures

Figure 1

12 pages, 2591 KiB  
Article
Ent-Peniciherqueinone Suppresses Acetaldehyde-Induced Cytotoxicity and Oxidative Stress by Inducing ALDH and Suppressing MAPK Signaling
by Taehoon Oh, Mincheol Kwon, Jae Sik Yu, Mina Jang, Gun-Hee Kim, Ki Hyun Kim, Sung-Kyun Ko and Jong Seog Ahn
Pharmaceutics 2020, 12(12), 1229; https://doi.org/10.3390/pharmaceutics12121229 - 18 Dec 2020
Cited by 7 | Viewed by 2547
Abstract
Studies on ethanol-induced stress and acetaldehyde toxicity are actively being conducted, owing to an increase in alcohol consumption in modern society. In this study, ent-peniciherqueinone (EPQ) isolated from a Hawaiian volcanic soil-associated fungus Penicillium herquei FT729 was found to reduce the acetaldehyde-induced [...] Read more.
Studies on ethanol-induced stress and acetaldehyde toxicity are actively being conducted, owing to an increase in alcohol consumption in modern society. In this study, ent-peniciherqueinone (EPQ) isolated from a Hawaiian volcanic soil-associated fungus Penicillium herquei FT729 was found to reduce the acetaldehyde-induced cytotoxicity and oxidative stress in PC12 cells. EPQ increased cell viability in the presence of acetaldehyde-induced cytotoxicity in PC12 cells. In addition, EPQ reduced cellular reactive oxygen species (ROS) levels and restored acetaldehyde-mediated disruption of mitochondrial membrane potential. Western blot analyses revealed that EPQ treatment increased protein levels of ROS-scavenging heme oxygenase-1 and superoxide dismutase, as well as the levels of aldehyde dehydrogenase (ALDH) 1, ALDH2, and ALDH3, under acetaldehyde-induced cellular stress. Finally, EPQ reduced acetaldehyde-induced phosphorylation of p38 and c-Jun N-terminal kinase, which are associated with ROS-induced oxidative stress. Therefore, our results demonstrated that EPQ prevents cellular oxidative stress caused by acetaldehyde and functions as a potent agent to suppress hangover symptoms and alcohol-related stress. Full article
(This article belongs to the Section Biologics and Biosimilars)
►▼ Show Figures

Graphical abstract

14 pages, 2065 KiB  
Article
The Influence of Increasing Concentrations of AMPD on the Efficacy of Its Penetration into a Model Skin Sebum Layer
by Agnieszka Kostrzębska and Witold Musiał
Pharmaceutics 2020, 12(12), 1228; https://doi.org/10.3390/pharmaceutics12121228 - 18 Dec 2020
Cited by 5 | Viewed by 1906
Abstract
Alcoholamines are widely used as auxiliary substances in various topical preparations. Their impact on the components of skin sebum allows them to be used in preparations that cleanse the skin of sebum in hair follicles. We measured the effects of various concentrations of [...] Read more.
Alcoholamines are widely used as auxiliary substances in various topical preparations. Their impact on the components of skin sebum allows them to be used in preparations that cleanse the skin of sebum in hair follicles. We measured the effects of various concentrations of aqueous solutions of AMPD (2-amino-2-methyl-1,3-propanediol) on model skin sebum. The volume of reacted sebum was calculated using two methods: optical assessment of the interaction of alcoholamines with the components of model skin sebum and determination of the reacted volume of model skin sebum based on the measurements of changes in the pH of the AMPD solutions. Both methods showed that the most favorable AMPD concentration for model sebum penetration was approximately 1–2%. Lower values of alcoholamine caused premature exhaustion from the solution. Excessively high concentrations resulted in the formation of a dense layer of products hindering effective skin cleansing. Full article
(This article belongs to the Special Issue Skin and Formulation)
►▼ Show Figures

Graphical abstract

8 pages, 12707 KiB  
Communication
Brain and Nasal Cavity Anatomy of the Cynomolgus Monkey: Species Differences from the Viewpoint of Direct Delivery from the Nose to the Brain
by Toshiyasu Sakane, Sachi Okabayashi, Shunsuke Kimura, Daisuke Inoue, Akiko Tanaka and Tomoyuki Furubayashi
Pharmaceutics 2020, 12(12), 1227; https://doi.org/10.3390/pharmaceutics12121227 - 18 Dec 2020
Cited by 8 | Viewed by 3517
Abstract
Based on structural data on the nasal cavity and brain of the cynomolgus monkey, species differences in the olfactory bulb and cribriform plate were discussed from the viewpoint of direct delivery from the nose to the brain. Structural 3D data on the cynomolgus [...] Read more.
Based on structural data on the nasal cavity and brain of the cynomolgus monkey, species differences in the olfactory bulb and cribriform plate were discussed from the viewpoint of direct delivery from the nose to the brain. Structural 3D data on the cynomolgus monkey skull were obtained using X-ray computed tomography. The dimensions of the nasal cavity of the cynomolgus monkey were 5 mm width × 20 mm height × 60 mm depth. The nasal cavity was very narrow and the olfactory region was far from the nostrils, similar to rats and humans. The weight and size of the monkey brain were 70 g and 55 mm width × 40 mm height × 70 mm depth. The olfactory bulb of monkeys is plate-like, while that of humans and rats is bulbar, suggesting that the olfactory area connected with the brain of monkeys is narrow. Although the structure of the monkey nasal cavity is similar to that of humans, the size and shape of the olfactory bulb are different, which is likely to result in low estimation of direct delivery from the nose to the brain in monkeys. Full article
(This article belongs to the Special Issue Nose to Brain Delivery (Volume II))
►▼ Show Figures

Graphical abstract

17 pages, 1933 KiB  
Article
Pharmacokinetic Characterization and External Evaluation of a Quantitative Framework of Sublingual Buprenorphine in Patients with an Opioid Disorder in Puerto Rico
by Darlene Santiago, Victor Mangas-Sanjuan, Kyle Melin, Jorge Duconge, Wenchen Zhao and Raman Venkataramanan
Pharmaceutics 2020, 12(12), 1226; https://doi.org/10.3390/pharmaceutics12121226 - 18 Dec 2020
Cited by 4 | Viewed by 2393
Abstract
Background: The aim of this analysis was to characterize the pharmacokinetics (PK) of sublingual buprenorphine (BUP) and its metabolites (buprenorphine glucuronide; BUP-g, norbuprenorphine; Nor-BUP, and norbuprenorphine glucuronide; Nor-BUP-g) in opioid use disorder (OUD) patients in Puerto Rico (PR) as a first step of [...] Read more.
Background: The aim of this analysis was to characterize the pharmacokinetics (PK) of sublingual buprenorphine (BUP) and its metabolites (buprenorphine glucuronide; BUP-g, norbuprenorphine; Nor-BUP, and norbuprenorphine glucuronide; Nor-BUP-g) in opioid use disorder (OUD) patients in Puerto Rico (PR) as a first step of evidence-based BUP dosing strategies in this population. Methods: BUP and metabolites concentrations were measured from 0 to 8 h after the administration of sublingual buprenorphine/naloxone films in 12 stable OUD subjects. Results: PK non-compartmental characteristics showed considerable variability in parameters between the subjects over the 8-h sampling time (tmax = 1.5 ± 0.7 h, Co = 1.6 ± 1.4 ng/mL, Cmax= 7.1 ± 6 ng/mL, and AUC0–8h = 26.8 ± 17.8 h·ng/mL). Subjects had a significantly higher tendency towards CYP-mediated N-demethylation, with the AUC0–8h ratios of the molar concentrations of [Nor-BUP + Nor-BUP-g] to BUP being (3.4 ± 1.9) significantly higher compared with BUP-g to BUP (0.19 ± 0.2). A two-compartment population-PK model with linear absorption (ka = 2.54 h−1), distribution (k12= 2.34 h−1, k14 = 1.29 h−1), metabolism (k24 = 1.28 × 10−1 h−1, k23 = 6.43 × 10−2 h−1, k35 = 1.23 × 10−1 h−1, k45 = 8.73 × 10−1 h−1), and elimination (k30 = 3.81 × 10−3 h−1, k50 = 1.27 × 10−1 h−1) adequately described the time-course of BUP and its metabolites, which has been externally validated using published data. Conclusions: Although limited in sampling time and number of recruited subjects, this study presents specific BUP PK characteristics that evidenced the need for additional PK studies and subsequent modeling of the data for the development of evidence-based dosing approaches in Puerto Rico. Full article
(This article belongs to the Special Issue The Role of Pharmacometrics in Drug Discovery and Development Process)
►▼ Show Figures

Figure 1

22 pages, 3440 KiB  
Article
Intranasal 17β-Estradiol Modulates Spatial Learning and Memory in a Rat Model of Surgical Menopause
by Alesia V. Prakapenka, Veronica L. Peña, Isabel Strouse, Steven Northup-Smith, Ally Schrier, Kinza Ahmed, Heather A. Bimonte-Nelson and Rachael W. Sirianni
Pharmaceutics 2020, 12(12), 1225; https://doi.org/10.3390/pharmaceutics12121225 - 17 Dec 2020
Cited by 5 | Viewed by 2508
Abstract
Exogenously administered 17β-estradiol (E2) can improve spatial learning and memory, although E2 also exerts undesired effects on peripheral organs. Clinically, E2 has been solubilized in cyclodextrin for intranasal administration, which enhances brain-specific delivery. Prior work shows that the cyclodextrin structure impacts region-specific brain [...] Read more.
Exogenously administered 17β-estradiol (E2) can improve spatial learning and memory, although E2 also exerts undesired effects on peripheral organs. Clinically, E2 has been solubilized in cyclodextrin for intranasal administration, which enhances brain-specific delivery. Prior work shows that the cyclodextrin structure impacts region-specific brain distribution of intranasally administered small molecules. Here, we investigated (1) cyclodextrin type-specific modulation of intranasal E2 brain distribution, and (2) cognitive and peripheral tissue effects of intranasal E2 in middle-aged ovariectomized rats. First, brain and peripheral organ distribution of intranasally administered, tritiated E2 was measured for E2 solubilized freely or in one of four cyclodextrin formulations. The E2-cyclodextrin formulation with greatest E2 uptake in cognitive brain regions versus uterine horns was then compared to free E2 on learning, memory, and uterine measures. Free E2 improved spatial reference memory, whereas E2-cyclodextrin impaired spatial working memory compared to their respective controls. Both E2 formulations increased uterine horn weights relative to controls, with E2-cyclodextrin resulting in the greatest uterine horn weight, suggesting increased uterine stimulation. Thus, intranasal administration of freely solubilized E2 is a strategic delivery tool that can yield a cognitively beneficial impact of the hormone alongside decreased peripheral effects compared to intranasal administration of cyclodextrin solubilized E2. Full article
(This article belongs to the Special Issue Nose to Brain Delivery (Volume II))
►▼ Show Figures

Graphical abstract

13 pages, 1002 KiB  
Review
Supramolecular and Macromolecular Matrix Nanocarriers for Drug Delivery in Inflammation-Associated Skin Diseases
by Ranime Jebbawi, Séverine Fruchon, Cédric-Olivier Turrin, Muriel Blanzat and Rémy Poupot
Pharmaceutics 2020, 12(12), 1224; https://doi.org/10.3390/pharmaceutics12121224 - 17 Dec 2020
Cited by 3 | Viewed by 3092
Abstract
Skin is our biggest organ. It interfaces our body with its environment. It is an efficient barrier to control the loss of water, the regulation of temperature, and infections by skin-resident and environmental pathogens. The barrier function of the skin is played by [...] Read more.
Skin is our biggest organ. It interfaces our body with its environment. It is an efficient barrier to control the loss of water, the regulation of temperature, and infections by skin-resident and environmental pathogens. The barrier function of the skin is played by the stratum corneum (SC). It is a lipid barrier associating corneocytes (the terminally differentiated keratinocytes) and multilamellar lipid bilayers. This intricate association constitutes a very cohesive system, fully adapted to its role. One consequence of this efficient organization is the virtual impossibility for active pharmaceutical ingredients (API) to cross the SC to reach the inner layers of the skin after topical deposition. There are several ways to help a drug to cross the SC. Physical methods and chemical enhancers of permeation are a possibility. These are invasive and irritating methods. Vectorization of the drugs through nanocarriers is another way to circumvent the SC. This mini-review focuses on supramolecular and macromolecular matrices designed and implemented for skin permeation, excluding vesicular nanocarriers. Examples highlight the entrapment of anti-inflammatory API to treat inflammatory disorders of the skin. Full article
(This article belongs to the Special Issue Emerging Nanocarriers-Based Drug Delivery in Inflammation-Associated Diseases)
►▼ Show Figures

Figure 1

21 pages, 2364 KiB  
Article
Studies on the Effect of Oil and Surfactant on the Formation of Alginate-Based O/W Lidocaine Nanocarriers Using Nanoemulsion Template
by Omar Sarheed, Manar Dibi and Kanteti V. R. N. S. Ramesh
Pharmaceutics 2020, 12(12), 1223; https://doi.org/10.3390/pharmaceutics12121223 - 17 Dec 2020
Cited by 75 | Viewed by 4087
Abstract
The application of various nanocarrier systems was widely explored in the field of pharmaceuticals to achieve better drug encapsulation and delivery. The aim of this study was to encapsulate lidocaine in alginate-based o/w nanocarriers based on the type of oil (i.e., solid or [...] Read more.
The application of various nanocarrier systems was widely explored in the field of pharmaceuticals to achieve better drug encapsulation and delivery. The aim of this study was to encapsulate lidocaine in alginate-based o/w nanocarriers based on the type of oil (i.e., solid or liquid), using a nanoemulsion template prepared by ultrasound-assisted phase inversion temperature (PIT) approach. The nanoemulsion template was initially prepared by dissolving lidocaine in the oil phase and surfactant and alginate in the aqueous phase, and keeping the PIT at around 85 °C, accompanied by gradual water dilution at 25 °C, to initiate the formation of nanoparticles (o/w) with the aid of low frequency ultrasound. The composition and concentration of the oil phase had a major impact on the particle size and led to an increase in the size of the droplet. The lipids that showed a higher drug solubility also showed higher particle size. On the other hand, increasing the concentration of surfactant decreases the size of the droplet before the concentration of the surfactant exceeds the limit, after which the size of the particle increases due to the aggregates that could be produced from the excess surfactant. The method used produced nanoemulsions that maintained nano-sized droplets < 50 nm, over long-term storage. Our findings are important for the design of nanocarrier systems for the encapsulation of lipophilic molecules. Full article
(This article belongs to the Special Issue Microencapsulation for the Therapeutic Delivery of Drugs)
►▼ Show Figures

Figure 1

24 pages, 1365 KiB  
Review
Neutrophils and Macrophages as Targets for Development of Nanotherapeutics in Inflammatory Diseases
by Yujie Su, Jin Gao, Puneet Kaur and Zhenjia Wang
Pharmaceutics 2020, 12(12), 1222; https://doi.org/10.3390/pharmaceutics12121222 - 17 Dec 2020
Cited by 55 | Viewed by 5827
Abstract
Neutrophils and macrophages are major components of innate systems, playing central roles in inflammation responses to infections and tissue injury. If they are out of control, inflammation responses can cause the pathogenesis of a wide range of diseases, such as inflammatory disorders and [...] Read more.
Neutrophils and macrophages are major components of innate systems, playing central roles in inflammation responses to infections and tissue injury. If they are out of control, inflammation responses can cause the pathogenesis of a wide range of diseases, such as inflammatory disorders and autoimmune diseases. Precisely regulating the functions of neutrophils and macrophages in vivo is a potential strategy to develop immunotherapies to treat inflammatory diseases. Advances in nanotechnology have enabled us to design nanoparticles capable of targeting neutrophils or macrophages in vivo. This review discusses the current status of how nanoparticles specifically target neutrophils or macrophages and how they manipulate leukocyte functions to inhibit their activation for inflammation resolution or to restore their defense ability for pathogen clearance. Finally, we present a novel concept of hijacking leukocytes to deliver nanotherapeutics across the blood vessel barrier. This review highlights the challenges and opportunities in developing nanotherapeutics to target leukocytes for improved treatment of inflammatory diseases. Full article
(This article belongs to the Special Issue Emerging Nanocarriers-Based Drug Delivery in Inflammation-Associated Diseases)
►▼ Show Figures

Figure 1

8 pages, 979 KiB  
Reply
Reply to “Comment on López-Yerena et al. ‘Absorption and Intestinal Metabolic Profile of Oleocanthal in Rats’ Pharmaceutics 2020, 12, 134”
by Anallely López-Yerena, Anna Vallverdú-Queralt, Raf Mols, Patrick Augustijns, Rosa M. Lamuela-Raventós and Elvira Escribano-Ferrer
Pharmaceutics 2020, 12(12), 1221; https://doi.org/10.3390/pharmaceutics12121221 - 17 Dec 2020
Cited by 2 | Viewed by 1627
Abstract
Recently, in February 2020, we published a study exploring the intestinal absorption and metabolism of oleocanthal (OLC) in rats. A single-pass intestinal perfusion technique (SPIP) was used, involving simultaneous sampling from the luminal perfusate and mesenteric blood. Later, comments on our published paper [...] Read more.
Recently, in February 2020, we published a study exploring the intestinal absorption and metabolism of oleocanthal (OLC) in rats. A single-pass intestinal perfusion technique (SPIP) was used, involving simultaneous sampling from the luminal perfusate and mesenteric blood. Later, comments on our published paper were released, requesting clarification of specific data. In this detailed reply, we hope to have addressed and clarified all the concerns of A. Kaddoumi and K. El Sayed and that the scientific community will benefit from both the study and the comments it has generated. Full article
(This article belongs to the Special Issue Intestinal Drug Absorption)
►▼ Show Figures

Figure 1

2 pages, 197 KiB  
Correction
Correction: López-Yerena, A., et al. “Absorption and Intestinal Metabolic Profile of Oleocanthal in Rats” Pharmaceutics 2020, 12, 134
by Anallely López-Yerena, Anna Vallverdú-Queralt, Raf Mols, Patrick Augustijns, Rosa M. Lamuela-Raventós and Elvira Escribano-Ferrer
Pharmaceutics 2020, 12(12), 1220; https://doi.org/10.3390/pharmaceutics12121220 - 17 Dec 2020
Cited by 2 | Viewed by 1475
Abstract
The authors would like to make the following corrections to this paper [...] Full article
(This article belongs to the Special Issue Intestinal Drug Absorption)
16 pages, 3727 KiB  
Article
In Vivo Bactericidal Efficacy of GWH1 Antimicrobial Peptide Displayed on Protein Nanoparticles, a Potential Alternative to Antibiotics
by Jose V. Carratalá, Eric Brouillette, Naroa Serna, Alejandro Sánchez-Chardi, Julieta M. Sánchez, Antonio Villaverde, Anna Arís, Elena Garcia-Fruitós, Neus Ferrer-Miralles and François Malouin
Pharmaceutics 2020, 12(12), 1217; https://doi.org/10.3390/pharmaceutics12121217 - 17 Dec 2020
Cited by 8 | Viewed by 2900
Abstract
Oligomerization of antimicrobial peptides into nanosized supramolecular complexes produced in biological systems (inclusion bodies and self-assembling nanoparticles) seems an appealing alternative to conventional antibiotics. In this work, the antimicrobial peptide, GWH1, was N-terminally fused to two different scaffold proteins, namely, GFP and IFN-γ [...] Read more.
Oligomerization of antimicrobial peptides into nanosized supramolecular complexes produced in biological systems (inclusion bodies and self-assembling nanoparticles) seems an appealing alternative to conventional antibiotics. In this work, the antimicrobial peptide, GWH1, was N-terminally fused to two different scaffold proteins, namely, GFP and IFN-γ for its bacterial production in the form of such recombinant protein complexes. Protein self-assembling as regular soluble protein nanoparticles was achieved in the case of GWH1-GFP, while oligomerization into bacterial inclusion bodies was reached in both constructions. Among all these types of therapeutic proteins, protein nanoparticles of GWH1-GFP showed the highest bactericidal effect in an in vitro assay against Escherichia coli, whereas non-oligomerized GWH1-GFP and GWH1-IFN-γ only displayed a moderate bactericidal activity. These results indicate that the biological activity of GWH1 is specifically enhanced in the form of regular multi-display configurations. Those in vitro observations were fully validated against a bacterial infection using a mouse mastitis model, in which the GWH1-GFP soluble nanoparticles were able to effectively reduce bacterial loads. Full article
►▼ Show Figures

Graphical abstract

24 pages, 7137 KiB  
Article
Layered Double Hydroxide as a Potent Non-viral Vector for Nucleic Acid Delivery Using Gene-Activated Scaffolds for Tissue Regeneration Applications
by Lara S. Costard, Domhnall C. Kelly, Rachael N. Power, Christopher Hobbs, Sonia Jaskaniec, Valeria Nicolosi, Brenton L. Cavanagh, Caroline M. Curtin and Fergal J. O’Brien
Pharmaceutics 2020, 12(12), 1219; https://doi.org/10.3390/pharmaceutics12121219 - 16 Dec 2020
Cited by 25 | Viewed by 4245
Abstract
Nonviral vectors offer a safe alternative to viral vectors for gene therapy applications, albeit typically exhibiting lower transfection efficiencies. As a result, there remains a significant need for the development of a nonviral delivery system with low cytotoxicity and high transfection efficacy as [...] Read more.
Nonviral vectors offer a safe alternative to viral vectors for gene therapy applications, albeit typically exhibiting lower transfection efficiencies. As a result, there remains a significant need for the development of a nonviral delivery system with low cytotoxicity and high transfection efficacy as a tool for safe and transient gene delivery. This study assesses MgAl-NO3 layered double hydroxide (LDH) as a nonviral vector to deliver nucleic acids (pDNA, miRNA and siRNA) to mesenchymal stromal cells (MSCs) in 2D culture and using a 3D tissue engineering scaffold approach. Nanoparticles were formulated by complexing LDH with pDNA, microRNA (miRNA) mimics and inhibitors, and siRNA at varying mass ratios of LDH:nucleic acid. In 2D monolayer, pDNA delivery demonstrated significant cytotoxicity issues, and low cellular transfection was deemed to be a result of the poor physicochemical properties of the LDH–pDNA nanoparticles. However, the lower mass ratios required to successfully complex with miRNA and siRNA cargo allowed for efficient delivery to MSCs. Furthermore, incorporation of LDH–miRNA nanoparticles into collagen-nanohydroxyapatite scaffolds resulted in successful overexpression of miRNA in MSCs, demonstrating the development of an efficacious miRNA delivery platform for gene therapy applications in regenerative medicine. Full article
(This article belongs to the Special Issue Novel Nanoparticles for Targeted Delivery of Therapeutic Nucleic Acids)
►▼ Show Figures

Graphical abstract

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-117
Previous Issue
Next Issue
Back to TopTop