Next Issue
Volume 13, October
Previous Issue
Volume 13, August
 
 

Pharmaceutics, Volume 13, Issue 9 (September 2021) – 205 articles

Cover Story (view full-size image): Among the emerging strategies in the treatment of cancer, stimuli-responsive smart drug delivery systems have attracted attention because of the efficient delivery of the payload at the target site without harming the healthy tissues and simultaneously coping with chemoresistance due to subtherapeutic drug exposures. Apart from their salient features, liposomes and mesoporous silica nanoparticles individually exhibit certain drawbacks, but a combined approach ends up being a success. The gatekeeping effect of lipid coat not only plays an important role in the stability of nanocarriers but also enhances the cellular uptake. Ultrasound responsive conversion of liquid to gas result in lipid layer rupture and ultimately triggers drug release from porous structures. 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
Select all
Export citation of selected articles as:
32 pages, 23622 KiB  
Review
Optimizing Spray-Dried Porous Particles for High Dose Delivery with a Portable Dry Powder Inhaler
by Yoen-Ju Son, Danforth P. Miller and Jeffry G. Weers
Pharmaceutics 2021, 13(9), 1528; https://doi.org/10.3390/pharmaceutics13091528 - 21 Sep 2021
Cited by 10 | Viewed by 3949
Abstract
This manuscript critically reviews the design and delivery of spray-dried particles for the achievement of high total lung doses (TLD) with a portable dry powder inhaler. We introduce a new metric termed the product density, which is simply the [...] Read more.
This manuscript critically reviews the design and delivery of spray-dried particles for the achievement of high total lung doses (TLD) with a portable dry powder inhaler. We introduce a new metric termed the product density, which is simply the TLD of a drug divided by the volume of the receptacle it is contained within. The product density is given by the product of three terms: the packing density (the mass of powder divided by the volume of the receptacle), the drug loading (the mass of drug divided by the mass of powder), and the aerosol performance (the TLD divided by the mass of drug). This manuscript discusses strategies for maximizing each of these terms. Spray drying at low drying rates with small amounts of a shell-forming excipient (low Peclet number) leads to the formation of higher density particles with high packing densities. This enables ultrahigh TLD (>100 mg of drug) to be achieved from a single receptacle. The emptying of powder from capsules is directly proportional to the mass of powder in the receptacle, requiring an inhaled volume of about 1 L for fill masses between 40 and 50 mg and up to 3.2 L for a fill mass of 150 mg. Full article
(This article belongs to the Special Issue Inhaled Treatment of Respiratory Infections)
Show Figures

Figure 1

20 pages, 6611 KiB  
Article
Multifunctional Nanofibrous Dressing with Antimicrobial and Anti-Inflammatory Properties Prepared by Needle-Free Electrospinning
by Laura Victoria Schulte-Werning, Anjanah Murugaiah, Bhupender Singh, Mona Johannessen, Rolf Einar Engstad, Nataša Škalko-Basnet and Ann Mari Holsæter
Pharmaceutics 2021, 13(9), 1527; https://doi.org/10.3390/pharmaceutics13091527 - 21 Sep 2021
Cited by 11 | Viewed by 2974
Abstract
An active wound dressing should address the main goals in wound treatment, which are improved wound healing and reduced infection rates. We developed novel multifunctional nanofibrous wound dressings with three active ingredients: chloramphenicol (CAM), beta-glucan (βG) and chitosan (CHI), of which βG and [...] Read more.
An active wound dressing should address the main goals in wound treatment, which are improved wound healing and reduced infection rates. We developed novel multifunctional nanofibrous wound dressings with three active ingredients: chloramphenicol (CAM), beta-glucan (βG) and chitosan (CHI), of which βG and CHI are active nanofiber-forming biopolymers isolated from the cell walls of Saccharomyces cerevisiae and from shrimp shells, respectively. To evaluate the effect of each active ingredient on the nanofibers’ morphological features and bioactivity, nanofibers with both βG and CHI, only βG, only CHI and only copolymers, polyethylene oxide (PEO) and hydroxypropylmethylcellulose (HPMC) were fabricated. All four nanofiber formulations were also prepared with 1% CAM. The needle-free NanospiderTM technique allowed for the successful production of defect-free nanofibers containing all three active ingredients. The CAM-containing nanofibers had a burst CAM-release and a high absorption capacity. Nanofibers with all active ingredients (βG, CHI and CAM) showed a concentration-dependent anti-inflammatory activity, while maintaining the antimicrobial activity of CAM. The promising anti-inflammatory properties, together with the high absorption capacity and antimicrobial effect, make these multifunctional nanofibers promising as dressings in local treatment of infected and exuding wounds, such as burn wounds. Full article
Show Figures

Graphical abstract

18 pages, 3158 KiB  
Article
Endothelial-Derived Extracellular Vesicles Induce Cerebrovascular Dysfunction in Inflammation
by David Roig-Carles, Eduard Willms, Ruud D. Fontijn, Sarai Martinez-Pacheco, Imre Mäger, Helga E. de Vries, Mark Hirst, Basil Sharrack, David K. Male, Cheryl A. Hawkes and Ignacio A. Romero
Pharmaceutics 2021, 13(9), 1525; https://doi.org/10.3390/pharmaceutics13091525 - 21 Sep 2021
Cited by 16 | Viewed by 3388
Abstract
Blood–brain barrier (BBB) dysfunction is a key hallmark in the pathology of many neuroinflammatory disorders. Extracellular vesicles (EVs) are lipid membrane-enclosed carriers of molecular cargo that are involved in cell-to-cell communication. Circulating endothelial EVs are increased in the plasma of patients with neurological [...] Read more.
Blood–brain barrier (BBB) dysfunction is a key hallmark in the pathology of many neuroinflammatory disorders. Extracellular vesicles (EVs) are lipid membrane-enclosed carriers of molecular cargo that are involved in cell-to-cell communication. Circulating endothelial EVs are increased in the plasma of patients with neurological disorders, and immune cell-derived EVs are known to modulate cerebrovascular functions. However, little is known about whether brain endothelial cell (BEC)-derived EVs themselves contribute to BBB dysfunction. Human cerebral microvascular cells (hCMEC/D3) were treated with TNFα and IFNy, and the EVs were isolated and characterised. The effect of EVs on BBB transendothelial resistance (TEER) and leukocyte adhesion in hCMEC/D3 cells was measured by electric substrate cell-substrate impedance sensing and the flow-based T-cell adhesion assay. EV-induced molecular changes in recipient hCMEC/D3 cells were analysed by RT-qPCR and Western blotting. A stimulation of naïve hCMEC/D3 cells with small EVs (sEVs) reduced the TEER and increased the shear-resistant T-cell adhesion. The levels of microRNA-155, VCAM1 and ICAM1 were increased in sEV-treated hCMEC/D3 cells. Blocking the expression of VCAM1, but not of ICAM1, prevented sEV-mediated T-cell adhesion to brain endothelia. These results suggest that sEVs derived from inflamed BECs promote cerebrovascular dysfunction. These findings may provide new insights into the mechanisms involving neuroinflammatory disorders. Full article
(This article belongs to the Special Issue Biological Barriers in Health and Disease)
Show Figures

Figure 1

27 pages, 6328 KiB  
Review
3D Printing of Thermo-Sensitive Drugs
by Sadikalmahdi Abdella, Souha H. Youssef, Franklin Afinjuomo, Yunmei Song, Paris Fouladian, Richard Upton and Sanjay Garg
Pharmaceutics 2021, 13(9), 1524; https://doi.org/10.3390/pharmaceutics13091524 - 21 Sep 2021
Cited by 24 | Viewed by 5312
Abstract
Three-dimensional (3D) printing is among the rapidly evolving technologies with applications in many sectors. The pharmaceutical industry is no exception, and the approval of the first 3D-printed tablet (Spiratam®) marked a revolution in the field. Several studies reported the fabrication of [...] Read more.
Three-dimensional (3D) printing is among the rapidly evolving technologies with applications in many sectors. The pharmaceutical industry is no exception, and the approval of the first 3D-printed tablet (Spiratam®) marked a revolution in the field. Several studies reported the fabrication of different dosage forms using a range of 3D printing techniques. Thermosensitive drugs compose a considerable segment of available medications in the market requiring strict temperature control during processing to ensure their efficacy and safety. Heating involved in some of the 3D printing technologies raises concerns regarding the feasibility of the techniques for printing thermolabile drugs. Studies reported that semi-solid extrusion (SSE) is the commonly used printing technique to fabricate thermosensitive drugs. Digital light processing (DLP), binder jetting (BJ), and stereolithography (SLA) can also be used for the fabrication of thermosensitive drugs as they do not involve heating elements. Nonetheless, degradation of some drugs by light source used in the techniques was reported. Interestingly, fused deposition modelling (FDM) coupled with filling techniques offered protection against thermal degradation. Concepts such as selection of low melting point polymers, adjustment of printing parameters, and coupling of more than one printing technique were exploited in printing thermosensitive drugs. This systematic review presents challenges, 3DP procedures, and future directions of 3D printing of thermo-sensitive formulations. Full article
(This article belongs to the Special Issue Printed Pharmaceuticals in Future Healthcare)
Show Figures

Figure 1

10 pages, 1804 KiB  
Article
Tablet Splitting in Elderly Patients with Dementia: The Case of Quetiapine
by Roberta Ganzetti, Serena Logrippo, Matteo Sestili, Alessandro Caraffa, Marco Cespi, Giuseppe Pelliccioni, Paolo Blasi and Giulia Bonacucina
Pharmaceutics 2021, 13(9), 1523; https://doi.org/10.3390/pharmaceutics13091523 - 20 Sep 2021
Cited by 6 | Viewed by 4402
Abstract
Quetiapine is an atypical antipsychotic approved for treating schizophrenia, bipolar depression, and mania but is frequently used in an off-label manner to control the behavioral and psychological symptoms of dementia in elderly patients with dementia. Due to the need to personalize doses for [...] Read more.
Quetiapine is an atypical antipsychotic approved for treating schizophrenia, bipolar depression, and mania but is frequently used in an off-label manner to control the behavioral and psychological symptoms of dementia in elderly patients with dementia. Due to the need to personalize doses for elderly patients with dementia, quetiapine tablet manipulation is widespread in hospital settings, long-term care facilities, and patient homes. The aim of this study was to assess the impact of the different splitting techniques on quetiapine fumarate tablets by analysing the obtained sub-divided tablets and to discuss compliance with the European Pharmacopoeia limits on whole and split tablets. Quetiapine fumarate tablets of two dose strengths were taken at random (in a number able to assure a power of 0.8 during statistical comparison) and were split with a kitchen knife or tablet cutter. The weight and the drug content were determined for each half tablet. The obtained data were compared to the European Pharmacopoeia limits. The differences between the different splitting techniques were statistically tested. Data showed that split tablets, independently of the dose strength and the technique employed, were not compliant with the European Pharmacopoeia specifications for both entire and subdivided tablets in terms of weight and content uniformity. Thus, such a common practice could have potential effects on treatment efficacy and toxicity, especially when also considering the fragility of the elderly target population in which polypharmacotherapy is very common. These results indicate a compelling need for flexible quetiapine formulations that can assure more accurate dose personalization. Full article
(This article belongs to the Special Issue Advance in Development of Patient-Centric Dosage Form)
Show Figures

Graphical abstract

13 pages, 11708 KiB  
Review
Selinexor and the Selective Inhibition of Nuclear Export: A New Perspective on the Treatment of Sarcomas and Other Solid and Non-Solid Tumors
by Antonella Lucia Marretta, Giuseppe Di Lorenzo, Dario Ribera, Lucia Cannella, Claudia von Arx, Alessandra Bracigliano, Ottavia Clemente, Roberto Tafuto, Antonio Pizzolorusso and Salvatore Tafuto
Pharmaceutics 2021, 13(9), 1522; https://doi.org/10.3390/pharmaceutics13091522 - 20 Sep 2021
Cited by 5 | Viewed by 3489
Abstract
Nucleocytoplasmic transport has been found dysregulated in many types of cancer and is often described as a poor prognostic factor. Specifically, Exportin-1 (XPO1) has been found overexpressed in many tumors and has become an attractive target in molecular oncology and therapeutics development. The [...] Read more.
Nucleocytoplasmic transport has been found dysregulated in many types of cancer and is often described as a poor prognostic factor. Specifically, Exportin-1 (XPO1) has been found overexpressed in many tumors and has become an attractive target in molecular oncology and therapeutics development. The selective inhibitor of nuclear export, Selinexor, is one of the most scientifically interesting drugs that targets XPO1 in clinical development. In this review, we summarized the most relevant preclinical and clinical results achieved for non-solid tumors, sarcomas, and other kind of solid tumors. Full article
Show Figures

Graphical abstract

13 pages, 1931 KiB  
Article
Polylactide Nanocapsules Attenuate Adverse Cardiac Cellular Effects of Lyso-7, a Pan-PPAR Agonist/Anti-Inflammatory New Thiazolidinedione
by Giani M. Garcia, Jérôme Roy, Ivan R. Pitta, Dulcinéia S. P. Abdalla, Andrea Grabe-Guimarães, Vanessa C. F. Mosqueira and Sylvain Richard
Pharmaceutics 2021, 13(9), 1521; https://doi.org/10.3390/pharmaceutics13091521 - 20 Sep 2021
Cited by 3 | Viewed by 2176
Abstract
Lyso-7 is a novel synthetic thiazolidinedione, which is a receptor (pan) agonist of PPAR α,β/δ,γ with anti-inflammatory activity. We investigated the cardiotoxicity of free Lyso-7 in vitro (4.5–450 nM), and Lyso-7 loaded in polylactic acid nanocapsules (NC) in vivo (Lyso-7-NC, 1.6 mg/kg). In [...] Read more.
Lyso-7 is a novel synthetic thiazolidinedione, which is a receptor (pan) agonist of PPAR α,β/δ,γ with anti-inflammatory activity. We investigated the cardiotoxicity of free Lyso-7 in vitro (4.5–450 nM), and Lyso-7 loaded in polylactic acid nanocapsules (NC) in vivo (Lyso-7-NC, 1.6 mg/kg). In previous work, we characterized Lyso-7-NC. We administered intravenously Lyso-7, Lyso-7-NC, control, and blank-NC once a day for seven days in mice. We assessed cell contraction and intracellular Ca2+ transients on single mice cardiomyocytes enzymatically isolated. Lyso-7 reduced cell contraction and accelerated relaxation while lowering diastolic Ca2+ and reducing Ca2+ transient amplitude. Lyso-7 also promoted abnormal ectopic diastolic Ca2+ events, which isoproterenol dramatically enhanced. Incorporation of Lyso-7 in NC attenuated drug effects on cell contraction and prevented its impact on relaxation, diastolic Ca2+, Ca2+ transient amplitude, Ca2+ transient decay kinetics, and promotion of diastolic Ca2+ events. Acute effects of Lyso-7 on cardiomyocytes in vitro at high concentrations (450 nM) were globally similar to those observed after repeated administration in vivo. In conclusion, we show evidence for off-target effects of Lyso-7, seen during acute exposure of cardiomyocytes to high concentrations and after repeated treatment in mice. Nano-encapsulation of Lyso-7 in polymeric NC attenuated the unwanted effects, particularly ectopic Ca2+ events known to support life-threatening arrhythmias favored by stress or exercise. Full article
(This article belongs to the Special Issue Polymeric Nanocapsules in Drug Delivery)
Show Figures

Figure 1

24 pages, 1600 KiB  
Review
Non-Viral Gene Delivery Systems for Treatment of Myocardial Infarction: Targeting Strategies and Cardiac Cell Modulation
by Jieting Wang, Luying Yu, Ao Zhou, Jie Liu, Kai Wang, Ying Luo and Fang Wang
Pharmaceutics 2021, 13(9), 1520; https://doi.org/10.3390/pharmaceutics13091520 - 19 Sep 2021
Cited by 4 | Viewed by 3027
Abstract
Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality worldwide. Conventional therapies involving surgery or pharmacological strategies have shown limited therapeutic effects due to a lack of cardiac tissue repair. Gene therapy has opened an avenue for the treatment of cardiac [...] Read more.
Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality worldwide. Conventional therapies involving surgery or pharmacological strategies have shown limited therapeutic effects due to a lack of cardiac tissue repair. Gene therapy has opened an avenue for the treatment of cardiac diseases through manipulating the underlying gene mechanics. Several gene therapies for cardiac diseases have been assessed in clinical trials, while the clinical translation greatly depends on the delivery technologies. Non-viral vectors are attracting much attention due to their safety and facile production compared to viral vectors. In this review, we discuss the recent progress of non-viral gene therapies for the treatment of cardiovascular diseases, with a particular focus on myocardial infarction (MI). Through a summary of delivery strategies with which to target cardiac tissue and different cardiac cells for MI treatment, this review aims to inspire new insights into the design/exploitation of non-viral delivery systems for gene cargos to promote cardiac repair/regeneration. Full article
Show Figures

Figure 1

17 pages, 3216 KiB  
Article
Co-Spray Dried Nafamostat Mesylate with Lecithin and Mannitol as Respirable Microparticles for Targeted Pulmonary Delivery: Pharmacokinetics and Lung Distribution in Rats
by Ji-Hyun Kang, Young-Jin Kim, Min-Seok Yang, Dae Hwan Shin, Dong-Wook Kim, Il Yeong Park and Chun-Woong Park
Pharmaceutics 2021, 13(9), 1519; https://doi.org/10.3390/pharmaceutics13091519 - 19 Sep 2021
Cited by 10 | Viewed by 3141
Abstract
Coronavirus disease 2019 (COVID-19), caused by a new strain of coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading rapidly worldwide. Nafamostat mesylate (NFM) suppresses transmembrane serine protease 2 and SARS-CoV-2 S protein-mediated fusion. In this study, pharmacokinetics and lung distribution [...] Read more.
Coronavirus disease 2019 (COVID-19), caused by a new strain of coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading rapidly worldwide. Nafamostat mesylate (NFM) suppresses transmembrane serine protease 2 and SARS-CoV-2 S protein-mediated fusion. In this study, pharmacokinetics and lung distribution of NFM, administered via intravenous and intratracheal routes, were determined using high performance liquid chromatography analysis of blood plasma, lung lumen using bronchoalveolar lavage fluid, and lung tissue. Intratracheal administration had higher drug delivery and longer residual time in the lung lumen and tissue, which are the main sites of action, than intravenous administration. We confirmed the effect of lecithin as a stabilizer through an ex vivo stability test. Lecithin acts as an inhibitor of carboxylesterase and delays NFM decomposition. We prepared inhalable microparticles with NFM, lecithin, and mannitol via the co-spray method. The formulation prepared using an NFM:lecithin:mannitol ratio of 1:1:100 had a small particle size and excellent aerodynamic performance. Spray dried microparticles containing NFM, lecithin, and mannitol (1:1:100) had the longest residual time in the lung tissue. In conclusion, NFM-inhalable microparticles were prepared and confirmed to be delivered into the respiratory tract, such as lung lumen and lung tissue, through in vitro and in vivo evaluations. Full article
(This article belongs to the Special Issue Therapeutic Formulations of Repurposed Drugs against COVID-19)
Show Figures

Figure 1

18 pages, 8557 KiB  
Article
Mesoporous Calcium-Silicate Nanoparticles Loaded with Low-Dose Triton-100+Ag+ to Achieve Both Enhanced Antibacterial Properties and Low Cytotoxicity for Dentin Disinfection of Human Teeth
by Mengting Duan, Wei Fan and Bing Fan
Pharmaceutics 2021, 13(9), 1518; https://doi.org/10.3390/pharmaceutics13091518 - 19 Sep 2021
Cited by 3 | Viewed by 2540
Abstract
Mesoporous calcium-silicate nanoparticles (MCSNs) are excellent biomaterials for controlled drug delivery and mineralization induction. In this study, MCSNs were loaded with low-dose silver ion (Ag+) and Triton X-100 (TX-100) as the M-AgTX to achieve both enhanced antibacterial properties and low cytotoxicity [...] Read more.
Mesoporous calcium-silicate nanoparticles (MCSNs) are excellent biomaterials for controlled drug delivery and mineralization induction. In this study, MCSNs were loaded with low-dose silver ion (Ag+) and Triton X-100 (TX-100) as the M-AgTX to achieve both enhanced antibacterial properties and low cytotoxicity for dentin disinfection. The physicochemical property, biocompatibility, infiltration ability into dentinal tubules, anti-bacterial ability against both planktonic Enterococcusfaecalis (E. faecalis) and its biofilm on dentin, effects on dentin microhardness and in vitro mineralization property were systematically investigated. Results confirmed that the MCSNs and M-AgTX nanoparticles showed typical morphology of mesoporous materials and exhibited sustained release of chemicals with an alkaline pH value over time. M-AgTX also exhibited excellent biocompatibility on MC3T3-E1 cells and could eliminate 100% planktonic E. faecalis after 48-h treatment. On dentin slices, it could enter dentinal tubules by ultrasonic activation and inhibit the growth of E. faecalis on dentin. M-AgTX could completely inactive 28-day E. faecalis biofilm. TEM confirmed the destruction of cell membrane integrity and Ag+ infiltration into bacteria by M-AgTX. Besides, dentin slices medicated with M-AgTX nanoparticles displayed an increased microhardness. After being immersed in SBF for 7 days, apatite crystals could be observed on the surface of the material tablets. M-AgTX could be developed into a new multifunctional intra-canal medication or bone defect filling material for infected bone defects due to its sustained release profile, low cytotoxicity, infiltration ability, enhanced anti-bacterial and mineralization features. Full article
Show Figures

Figure 1

16 pages, 1978 KiB  
Article
Increased Bioavailability of β-Alanine by a Novel Controlled-Release Powder Blend Compared to a Slow-Release Tablet
by Lydia de Salazar, Ignacio Segarra, Francisco Javier López-Román, Antonio Torregrosa-García, Silvia Pérez-Piñero and Vicente Ávila-Gandía
Pharmaceutics 2021, 13(9), 1517; https://doi.org/10.3390/pharmaceutics13091517 - 19 Sep 2021
Cited by 3 | Viewed by 2780
Abstract
Background: β-Alanine is a sport supplement with increasing popularity due to its consistent ability to improve physical performance, with the downside of requiring several weeks of supplementation as imposed to the maximum daily and single dose tolerated without side effects (i.e., paresthesia). To [...] Read more.
Background: β-Alanine is a sport supplement with increasing popularity due to its consistent ability to improve physical performance, with the downside of requiring several weeks of supplementation as imposed to the maximum daily and single dose tolerated without side effects (i.e., paresthesia). To date, the only alternative to overcome this problem has been use of a sustained-release tablet, while powders are the most commonly used format to deliver several grams of amino acids in a single dose. In this study we assessed the bioavailability, pharmacokinetics and paresthesia effect of β-alanine after administration in a novel controlled-released powder blend (test) versus a sustained-release tablet (reference). Methods: Twelve subjects (25.6 ± 3.2 y, 50% female) participated in a randomized, single-blind, crossover study. Each participant was administered orally the test (β-alanine 8 g, l-histidine 300 mg, carnosine 100 mg) or the reference product (10 tablets to reach β-alanine 8 g, Zinc 20 mg) with a 1-week washout period. β-Alanine plasma concentrations (0–8 h) were determined by LC-MS/MS and model-independent pharmacokinetic analysis was carried out. Paresthesia intensity was evaluated using a Visual Analog Score (VAS) and the categorical Intensity Sensory Score (ISS). Results: The CMAX and AUC0 increased 1.6- and 2.1-fold (both p < 0.001) in the test product, respectively, which yielded 2.1-fold higher bioavailability; Ka decreased in the test (0.0199 ± 0.0107 min−1) versus the reference (0.0299 ± 0.0121 min−1) product (p = 0.0834) as well as V/F and Cl/F (both p < 0.001); MRT0→last increased in the test (143 ± 19 min) versus reference (128 ± 16 min) formulation (p = 0.0449); t1/2 remained similar (test: 63.5 ± 8.7 min, reference: 68.9 ± 9.8 min). Paresthesia EMAX increased 1.7-fold using the VAS (p = 0.086) and the ISS (p = 0.009). AUEC increased 1.9-fold with the VAS (p = 0.107) and the ISS (p = 0.019) reflecting scale intrinsic differences. Pharmacokinetic-pharmacodynamic analysis showed a clockwise hysteresis loop without prediction ability between CMAX, AUC0 and EMAX or AUEC. No side effects were reported (except paresthesia). Conclusions: The novel controlled-release powder blend shows 100% higher bioavailability of β-alanine, opening a new paradigm that shifts from chronic to short or mid-term supplementation strategies to increase carnosine stores in sports nutrition. Full article
(This article belongs to the Section Drug Delivery and Controlled Release)
Show Figures

Figure 1

14 pages, 1501 KiB  
Article
Synthesis and Biochemical Evaluation of Baicalein Prodrugs
by Sang-Hyun Son, Jinhong Kang, Myunghwan Ahn, Soyeon Nam, Yong Woo Jung, Ki Yong Lee, Young Ho Jeon, Youngjoo Byun and Kiho Lee
Pharmaceutics 2021, 13(9), 1516; https://doi.org/10.3390/pharmaceutics13091516 - 19 Sep 2021
Cited by 4 | Viewed by 3047
Abstract
Baicalein (5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one), a flavonoid analog from Scutellaria baicalensis, possesses several pharmacological activities including antioxidant, antiproliferative, and anti-inflammatory activities. We previously reported that baicalein inhibits the thymic stromal lymphopoietin (TSLP)/TSLP receptor (TSLPR) signaling pathways and can be used as an active ingredient in [...] Read more.
Baicalein (5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one), a flavonoid analog from Scutellaria baicalensis, possesses several pharmacological activities including antioxidant, antiproliferative, and anti-inflammatory activities. We previously reported that baicalein inhibits the thymic stromal lymphopoietin (TSLP)/TSLP receptor (TSLPR) signaling pathways and can be used as an active ingredient in the treatment of asthma and atopic dermatitis. However, baicalein is rapidly metabolized to baicalin and baicalein-6-O-glucuronide in vivo, which limits its preclinical and clinical use. In this study, we designed, synthesized, and evaluated baicalein prodrugs that protect the OH group at the 7-position of the A ring in baicalein with the amino acid carbamate functional group. Comprehensive in vitro and in vivo studies identified compound 2 as a baicalein prodrug candidate that improved the plasma exposure of baicalein in mouse animal studies. Our results demonstrated that this prodrug approach could be further adopted to discover oral baicalein prodrugs. Full article
Show Figures

Graphical abstract

20 pages, 5215 KiB  
Article
Cellulose Nanofibers Improve the Performance of Retrograded Starch/Pectin Microparticles for Colon-Specific Delivery of 5-ASA
by Andréia Bagliotti Meneguin, Rafael Miguel Sábio, Maurício Palmeira Chaves de Souza, Richard Perosa Fernandes, Anselmo Gomes de Oliveira and Marlus Chorilli
Pharmaceutics 2021, 13(9), 1515; https://doi.org/10.3390/pharmaceutics13091515 - 19 Sep 2021
Cited by 12 | Viewed by 2795
Abstract
Cellulose nanofibers (CNF) were employed as the nanoreinforcement of a retrograded starch/pectin (RS/P) excipient to optimize its colon-specific properties. Although starch retrogradation ranged from 32 to 73%, CNF addition discretely disfavored the RS yield. This result agrees with the finding that in situ [...] Read more.
Cellulose nanofibers (CNF) were employed as the nanoreinforcement of a retrograded starch/pectin (RS/P) excipient to optimize its colon-specific properties. Although starch retrogradation ranged from 32 to 73%, CNF addition discretely disfavored the RS yield. This result agrees with the finding that in situ CNF reduces the presence of the RS crystallinity pattern. A thermal analysis revealed that the contribution of pectin improves the thermal stability of the RS/CNF mixture. Through a complete factorial design, it was possible to optimize the spray-drying conditions to obtain powders with high yield (57%) and low moisture content (1.2%). The powders observed by Field Emission Gum Scanning Electron Microscopy (FEG-SEM) had 1–10 µm and a circular shape. The developed methodology allowed us to obtain 5-aminosalicilic acid-loaded microparticles with high encapsulation efficiency (16–98%) and drug loading (1.97–26.63%). The presence of CNF in RS/P samples was responsible for decreasing the burst effect of release in simulated gastric and duodenal media, allowing the greatest mass of drug to be targeted to the colon. Considering that spray-drying is a scalable process, widely used by the pharmaceutical industry, the results obtained indicate the potential of these microparticles as raw material for obtaining other dosage forms to deliver 5-ASA to the distal parts of gastrointestinal tract, affected by inflammatory bowel disease. Full article
Show Figures

Graphical abstract

26 pages, 723 KiB  
Article
Exploring Drugs and Vaccines Associated with Altered Risks and Severity of COVID-19: A UK Biobank Cohort Study of All ATC Level-4 Drug Categories Reveals Repositioning Opportunities
by Yong Xiang, Kenneth Chi-Yin Wong and Hon-Cheong So
Pharmaceutics 2021, 13(9), 1514; https://doi.org/10.3390/pharmaceutics13091514 - 18 Sep 2021
Cited by 10 | Viewed by 4159
Abstract
Effective therapies for COVID-19 are still lacking, and drug repositioning is a promising approach to address this problem. Here, we adopted a medical informatics approach to repositioning. We leveraged a large prospective cohort, the UK-Biobank (UKBB, N ~ 397,000), and studied associations of [...] Read more.
Effective therapies for COVID-19 are still lacking, and drug repositioning is a promising approach to address this problem. Here, we adopted a medical informatics approach to repositioning. We leveraged a large prospective cohort, the UK-Biobank (UKBB, N ~ 397,000), and studied associations of prior use of all level-4 ATC drug categories (N = 819, including vaccines) with COVID-19 diagnosis and severity. Effects of drugs on the risk of infection, disease severity, and mortality were investigated separately. Logistic regression was conducted, controlling for main confounders. We observed strong and highly consistent protective associations with statins. Many top-listed protective drugs were also cardiovascular medications, such as angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), calcium channel blocker (CCB), and beta-blockers. Some other drugs showing protective associations included biguanides (metformin), estrogens, thyroid hormones, proton pump inhibitors, and testosterone-5-alpha reductase inhibitors, among others. We also observed protective associations by influenza, pneumococcal, and several other vaccines. Subgroup and interaction analyses were also conducted, which revealed differences in protective effects in various subgroups. For example, protective effects of flu/pneumococcal vaccines were weaker in obese individuals, while protection by statins was stronger in cardiovascular patients. To conclude, our analysis revealed many drug repositioning candidates, for example several cardiovascular medications. Further studies are required for validation. Full article
(This article belongs to the Special Issue In Silico Strategies for Prospective Drug Repositionings)
Show Figures

Figure 1

14 pages, 1927 KiB  
Review
Functionalized Dendrimer Platforms as a New Forefront Arsenal Targeting SARS-CoV-2: An Opportunity
by Serge Mignani, Xiangyang Shi, Andrii Karpus, Giovanni Lentini and Jean-Pierre Majoral
Pharmaceutics 2021, 13(9), 1513; https://doi.org/10.3390/pharmaceutics13091513 - 18 Sep 2021
Cited by 13 | Viewed by 3263
Abstract
The novel human coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has caused a pandemic. There are currently several marketed vaccines and many in clinical trials targeting SARS-CoV-2. Another strategy is to repurpose approved drugs to decrease the burden of the COVID-19 (official [...] Read more.
The novel human coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has caused a pandemic. There are currently several marketed vaccines and many in clinical trials targeting SARS-CoV-2. Another strategy is to repurpose approved drugs to decrease the burden of the COVID-19 (official name for the coronavirus disease) pandemic. as the FDA (U.S. Food and Drug Administration) approved antiviral drugs and anti-inflammatory drugs to arrest the cytokine storm, inducing the production of pro-inflammatory cytokines. Another view to solve these unprecedented challenges is to analyze the diverse nanotechnological approaches which are able to improve the COVID-19 pandemic. In this original minireview, as promising candidates we analyze the opportunity to develop biocompatible dendrimers as drugs themselves or as nanocarriers against COVID-19 disease. From the standpoint of COVID-19, we suggest developing dendrimers as shields against COVID-19 infection based on their capacity to be incorporated in several environments outside the patients and as important means to stop transmission of SARS-CoV-2. Full article
(This article belongs to the Special Issue Dendrimers and Dendritic Materials against Infectious Diseases)
Show Figures

Graphical abstract

22 pages, 7940 KiB  
Article
Graphene Oxide and Graphene Quantum Dots as Delivery Systems of Cationic Porphyrins: Photo-Antiproliferative Activity Evaluation towards T24 Human Bladder Cancer Cells
by Luca Menilli, Ana R. Monteiro, Silvia Lazzarotto, Filipe M. P. Morais, Ana T. P. C. Gomes, Nuno M. M. Moura, Sara Fateixa, Maria A. F. Faustino, Maria G. P. M. S. Neves, Tito Trindade and Giorgia Miolo
Pharmaceutics 2021, 13(9), 1512; https://doi.org/10.3390/pharmaceutics13091512 - 18 Sep 2021
Cited by 19 | Viewed by 4368
Abstract
The development of new photodynamic therapy (PDT) agents designed for bladder cancer (BC) treatments is of utmost importance to prevent its recurrence and progression towards more invasive forms. Here, three different porphyrinic photosensitizers (PS) (TMPyP, Zn-TMPyP, and P1-C5) were non-covalently loaded [...] Read more.
The development of new photodynamic therapy (PDT) agents designed for bladder cancer (BC) treatments is of utmost importance to prevent its recurrence and progression towards more invasive forms. Here, three different porphyrinic photosensitizers (PS) (TMPyP, Zn-TMPyP, and P1-C5) were non-covalently loaded onto graphene oxide (GO) or graphene quantum dots (GQDs) in a one-step process. The cytotoxic effects of the free PS and of the corresponding hybrids were compared upon blue (BL) and red-light (RL) exposure on T24 human BC cells. In addition, intracellular reactive oxygen species (ROS) and singlet oxygen generation were measured. TMPyP and Zn-TMPyP showed higher efficiency under BL (IC50: 0.42 and 0.22 μm, respectively), while P1-C5 was more active under RL (IC50: 0.14 μm). In general, these PS could induce apoptotic cell death through lysosomes damage. The in vitro photosensitizing activity of the PS was not compromised after their immobilization onto graphene-based nanomaterials, with Zn-TMPyP@GQDs being the most promising hybrid system under RL (IC50: 0.37 μg/mL). Overall, our data confirm that GO and GQDs may represent valid platforms for PS delivery, without altering their performance for PDT on BC cells. Full article
(This article belongs to the Special Issue Drug Delivery in Photodynamic Therapy (PDT))
Show Figures

Graphical abstract

23 pages, 8094 KiB  
Article
Multifaced Role of Dual Herbal Principles Loaded-Lipid Nanocarriers in Providing High Therapeutic Efficacity
by Ioana Lacatusu, Teodora Alexandra Iordache, Mirela Mihaila, Dan Eduard Mihaiescu, Anca Lucia Pop and Nicoleta Badea
Pharmaceutics 2021, 13(9), 1511; https://doi.org/10.3390/pharmaceutics13091511 - 18 Sep 2021
Cited by 8 | Viewed by 2154
Abstract
Although many phytochemicals have been used in traditional medicine, there is a great need to refresh the health benefits and adjust the shortcomings of herbal medicine. In this research, two herbal principles (Diosgenin and Glycyrrhiza glabra extract) coopted in the Nanostructured Lipid Carriers [...] Read more.
Although many phytochemicals have been used in traditional medicine, there is a great need to refresh the health benefits and adjust the shortcomings of herbal medicine. In this research, two herbal principles (Diosgenin and Glycyrrhiza glabra extract) coopted in the Nanostructured Lipid Carriers have been developed for improving the most desirable properties of herbal medicine—antioxidant and anti-inflammatory actions. The contribution of phytochemicals, vegetable oils and of lipid matrices has been highlighted by comparative study of size, stability, entrapment efficiency, morphological characteristics, and thermal behavior. According to the in vitro MTS and RTCA results, the dual herbal-NLCs were no cytotoxic toward endothelial cells at concentrations between 25 and 100 µg/mL. A rapid release of Glycyrrhiza glabra and a motivated delay of Diosgenin was detected by the in vitro release experiments. Dual herbal-NLCs showed an elevated ability to annihilate long-life cationic radicals (ABTS•+) and short-life oxygenated radicals (an inhibition of 63.4% ABTS•+, while the ability to capture radical oxygen species reached 96%). The production of pro-inflammatory cytokines was significantly inhibited by the newly herbals-NLC (up to 97.9% inhibition of TNF-α and 62.5% for IL-6). The study may open a new pharmacotherapy horizon; it provides a comprehensive basis for the use of herbal-NLC in the treatment of inflammatory diseases. Full article
Show Figures

Graphical abstract

22 pages, 7663 KiB  
Article
Co-Injection of Sulfotyrosine Facilitates Retinal Uptake of Hyaluronic Acid Nanospheres Following Intravitreal Injection
by Aiden Eblimit, Mustafa S. Makia, Daniel Strayve, Ryan Crane, Shannon M. Conley, Tirthankar Sinha, Ghanashyam Acharya, Muayyad R. Al-Ubaidi and Muna I. Naash
Pharmaceutics 2021, 13(9), 1510; https://doi.org/10.3390/pharmaceutics13091510 - 18 Sep 2021
Cited by 2 | Viewed by 2490
Abstract
Gene and drug delivery to the retina is a critical therapeutic goal. While the majority of inherited forms of retinal degeneration affect the outer retina, specifically the photoreceptors and retinal pigment epithelium, effective targeted delivery to this region requires invasive subretinal delivery. Our [...] Read more.
Gene and drug delivery to the retina is a critical therapeutic goal. While the majority of inherited forms of retinal degeneration affect the outer retina, specifically the photoreceptors and retinal pigment epithelium, effective targeted delivery to this region requires invasive subretinal delivery. Our goal in this work was to evaluate two innovative approaches for increasing both the persistence of delivered nanospheres and their penetration into the outer retina while using the much less invasive intravitreal delivery method. We formulated novel hyaluronic acid nanospheres (HA-NS, 250 nm and 500 nm in diameter) conjugated to fluorescent reporters and delivered them intravitreally to the adult Balb/C mouse retina. They exhibited persistence in the vitreous and along the inner limiting membrane (ILM) for up to 30 days (longest timepoint examined) but little retinal penetration. We thus evaluated the ability of the small molecule, sulfotyrosine, to disrupt the ILM, and found that 3.2 µg/µL sulfotyrosine led to significant improvement in delivery to the outer retina following intravitreal injections without causing retinal inflammation, degeneration, or loss of function. Co-delivery of sulfotyrosine and HA-NS led to robust improvements in penetration of HA-NS into the retina and accumulation along the interface between the photoreceptors and the retinal pigment epithelium. These exciting findings suggest that sulfotyrosine and HA-NS may be an effective strategy for outer retinal targeting after intravitreal injection. Full article
Show Figures

Figure 1

37 pages, 1472 KiB  
Perspective
Inhibition of Scavenger Receptor Class B Type 1 (SR-B1) Expression and Activity as a Potential Novel Target to Disrupt Cholesterol Availability in Castration-Resistant Prostate Cancer
by Mitali Pandey, Grace Cuddihy, Jacob A. Gordon, Michael E. Cox and Kishor M. Wasan
Pharmaceutics 2021, 13(9), 1509; https://doi.org/10.3390/pharmaceutics13091509 - 18 Sep 2021
Cited by 2 | Viewed by 3325
Abstract
There have been several studies that have linked elevated scavenger receptor class b type 1 (SR-B1) expression and activity to the development and progression of castration-resistant prostate cancer (CRPC). SR-B1 facilitates the influx of cholesterol to the cell from lipoproteins in systemic circulation. [...] Read more.
There have been several studies that have linked elevated scavenger receptor class b type 1 (SR-B1) expression and activity to the development and progression of castration-resistant prostate cancer (CRPC). SR-B1 facilitates the influx of cholesterol to the cell from lipoproteins in systemic circulation. This influx of cholesterol may be important for many cellular functions, including the synthesis of androgens. Castration-resistant prostate cancer tumors can synthesize androgens de novo to supplement the loss of exogenous sources often induced by androgen deprivation therapy. Silencing of SR-B1 may impact the ability of prostate cancer cells, particularly those of the castration-resistant state, to maintain the intracellular supply of androgens by removing a supply of cholesterol. SR-B1 expression is elevated in CRPC models and has been linked to poor survival of patients. The overarching belief has been that cholesterol modulation, through either synthesis or uptake inhibition, will impact essential signaling processes, impeding the proliferation of prostate cancer. The reduction in cellular cholesterol availability can impede prostate cancer proliferation through both decreased steroid synthesis and steroid-independent mechanisms, providing a potential therapeutic target for the treatment of prostate cancer. In this article, we discuss and highlight the work on SR-B1 as a potential novel drug target for CRPC management. Full article
(This article belongs to the Collection Pharmaceutical Sciences in Canada)
Show Figures

Figure 1

22 pages, 4276 KiB  
Article
mPEG-PLGA Nanoparticles Labelled with Loaded or Conjugated Rhodamine-B for Potential Nose-to-Brain Delivery
by Emanuela Fabiola Craparo, Teresa Musumeci, Angela Bonaccorso, Rosalia Pellitteri, Alessia Romeo, Irina Naletova, Lorena Maria Cucci, Gennara Cavallaro and Cristina Satriano
Pharmaceutics 2021, 13(9), 1508; https://doi.org/10.3390/pharmaceutics13091508 - 18 Sep 2021
Cited by 16 | Viewed by 3473
Abstract
Nowdays, neurodegenerative diseases represent a great challenge from both the therapeutic and diagnostic points of view. Indeed, several physiological barriers of the body, including the blood brain barrier (BBB), nasal, dermal, and intestinal barriers, interpose between the development of new drugs and their [...] Read more.
Nowdays, neurodegenerative diseases represent a great challenge from both the therapeutic and diagnostic points of view. Indeed, several physiological barriers of the body, including the blood brain barrier (BBB), nasal, dermal, and intestinal barriers, interpose between the development of new drugs and their effective administration to reach the target organ or target cells at therapeutic concentrations. Currently, the nose-to-brain delivery with nanoformulations specifically designed for intranasal administration is a strategy widely investigated with the goal to reach the brain while bypassing the BBB. To produce nanosystems suitable to study both in vitro and/or in vivo cells trafficking for potential nose-to-brain delivery route, we prepared and characterized two types of fluorescent poly(ethylene glycol)-methyl-ether-block-poly(lactide-co-glycolide) (PLGA–PEG) nanoparticles (PNPs), i.e., Rhodamine B (RhB) dye loaded- and grafted- PNPs, respectively. The latter were produced by blending into the PLGA–PEG matrix a RhB-labeled polyaspartamide/polylactide graft copolymer to ensure a stable fluorescence during the time of analysis. Photon correlation spectroscopy (PCS), UV-visible (UV-vis) spectroscopies, differential scanning calorimetry (DSC), atomic force microscopy (AFM) were used to characterize the RhB-loaded and RhB-grafted PNPs. To assess their potential use for brain targeting, cytotoxicity tests were carried out on olfactory ensheathing cells (OECs) and neuron-like differentiated PC12 cells. Both PNP types showed mean sizes suitable for nose-to-brain delivery (<200 nm, PDI < 0.3) and were not cytotoxic toward OECs in the concentration range tested, while a reduction in the viability on PC12 cells was found when higher concentrations of nanomedicines were used. Both the RhB-labelled NPs are suitable drug carrier models for exploring cellular trafficking in nose-to-brain delivery for short-time or long-term studies. Full article
(This article belongs to the Special Issue Lipid- and/or Polymer-Based Drug Delivery Systems)
Show Figures

Graphical abstract

16 pages, 1420 KiB  
Article
Modulation of Colorectal Tumor Behavior via lncRNA TP53TG1-Lipidic Nanosystem
by Farimah Masoumi, Sofia M. Saraiva, Belén L. Bouzo, Rafael López-López, Manel Esteller, Ángel Díaz-Lagares and María de la Fuente
Pharmaceutics 2021, 13(9), 1507; https://doi.org/10.3390/pharmaceutics13091507 - 18 Sep 2021
Cited by 4 | Viewed by 3043
Abstract
Long non-coding RNAs (lncRNAs) are an emerging group of RNAs with a crucial role in cancer pathogenesis. In gastrointestinal cancers, TP53 target 1 (TP53TG1) is an epigenetically regulated lncRNA that represents a promising therapeutic target due to its tumor suppressor properties regulating the [...] Read more.
Long non-coding RNAs (lncRNAs) are an emerging group of RNAs with a crucial role in cancer pathogenesis. In gastrointestinal cancers, TP53 target 1 (TP53TG1) is an epigenetically regulated lncRNA that represents a promising therapeutic target due to its tumor suppressor properties regulating the p53-mediated DNA damage and the intracellular localization of the oncogenic YBX1 protein. However, to translate this finding into the clinic as a gene therapy, it is important to develop effective carriers able to deliver exogenous lncRNAs to the targeted cancer cells. Here, we propose the use of biocompatible sphingomyelin nanosystems comprising DOTAP (DSNs) to carry and deliver a plasmid vector encoding for TP53TG1 (pc(TP53TG1)-DSNs) to a colorectal cancer cell line (HCT-116). DSNs presented a high association capacity and convenient physicochemical properties. In addition, pc(TP53TG1)-DSNs showed anti-tumor activities in vitro, specifically a decrease in the proliferation rate, a diminished colony-forming capacity, and hampered migration and invasiveness of the treated cancer cells. Consequently, the proposed strategy displays a high potential as a therapeutic approach for colorectal cancer. Full article
(This article belongs to the Special Issue Non-viral Gene Delivery Systems, 2nd Edition)
Show Figures

Figure 1

21 pages, 3745 KiB  
Article
Systemically Administered Homing Peptide Targets Dystrophic Lesions and Delivers Transforming Growth Factor-β (TGFβ) Inhibitor to Attenuate Murine Muscular Dystrophy Pathology
by Aqsa Iqbal, Ulrike May, Stuart N. Prince, Tero A.H. Järvinen and Ahlke Heydemann
Pharmaceutics 2021, 13(9), 1506; https://doi.org/10.3390/pharmaceutics13091506 - 18 Sep 2021
Cited by 7 | Viewed by 2932
Abstract
Muscular dystrophy is a progressively worsening and lethal disease, where accumulation of functionality-impairing fibrosis plays a key pathogenic role. Transforming growth factor-β1 (TGFβ1) is a central signaling molecule in the development of fibrosis in muscular dystrophic humans and mice. Inhibition of TGFβ1 has [...] Read more.
Muscular dystrophy is a progressively worsening and lethal disease, where accumulation of functionality-impairing fibrosis plays a key pathogenic role. Transforming growth factor-β1 (TGFβ1) is a central signaling molecule in the development of fibrosis in muscular dystrophic humans and mice. Inhibition of TGFβ1 has proven beneficial in mouse models of muscular dystrophy, but the global strategies of TGFβ1 inhibition produce significant detrimental side effects. Here, we investigated whether murine muscular dystrophy lesion-specific inhibition of TGFβ1 signaling by the targeted delivery of therapeutic decorin (a natural TGFβ inhibitor) by a vascular homing peptide CAR (CARSKNKDC) would reduce skeletal muscle fibrosis and pathology and increase functional characteristics of skeletal muscle. We demonstrate that CAR peptide homes to dystrophic lesions with specificity in two muscular dystrophy models. Recombinant fusion protein consisting of CAR peptide and decorin homes selectively to sites of skeletal muscle damage in mdxDBA2/J and gamma-sarcoglycan deficient DBA2/J mice. This targeted delivery reduced TGFβ1 signaling as demonstrated by reduced nuclear pSMAD staining. Three weeks of targeted decorin treatment decreased both membrane permeability and fibrosis and improved skeletal muscle function in comparison to control treatments in the mdxD2 mice. These results show that selective delivery of decorin to the sites of skeletal muscle damage attenuates the progression of murine muscular dystrophy. Full article
(This article belongs to the Special Issue Precision Delivery of Drugs and Imaging Agents with Peptides)
Show Figures

Graphical abstract

15 pages, 1648 KiB  
Article
Optimisation of a Microfluidic Method for the Delivery of a Small Peptide
by Felicity Y. Han, Weizhi Xu, Vinod Kumar, Cedric S. Cui, Xaria Li, Xingyu Jiang, Trent M. Woodruff, Andrew K. Whittaker and Maree T. Smith
Pharmaceutics 2021, 13(9), 1505; https://doi.org/10.3390/pharmaceutics13091505 - 18 Sep 2021
Cited by 3 | Viewed by 3506
Abstract
Peptides hold promise as therapeutics, as they have high bioactivity and specificity, good aqueous solubility, and low toxicity. However, they typically suffer from short circulation half-lives in the body. To address this issue, here, we have developed a method for encapsulation of an [...] Read more.
Peptides hold promise as therapeutics, as they have high bioactivity and specificity, good aqueous solubility, and low toxicity. However, they typically suffer from short circulation half-lives in the body. To address this issue, here, we have developed a method for encapsulation of an innate-immune targeted hexapeptide into nanoparticles using safe non-toxic FDA-approved materials. Peptide-loaded nanoparticles were formulated using a two-stage microfluidic chip. Microfluidic-related factors (i.e., flow rate, organic solvent, theoretical drug loading, PLGA type, and concentration) that may potentially influence the nanoparticle properties were systematically investigated using dynamic light scattering and transmission electron microscopy. The pharmacokinetic (PK) profile and biodistribution of the optimised nanoparticles were assessed in mice. Peptide-loaded lipid shell-PLGA core nanoparticles with designated size (~400 nm) and a sustained in vitro release profile were further characterized in vivo. In the form of nanoparticles, the elimination half-life of the encapsulated peptide was extended significantly compared with the peptide alone and resulted in a much higher distribution into the lung. These novel nanoparticles with lipid shells have considerable potential for increasing the circulation half-life and improving the biodistribution of therapeutic peptides to improve their clinical utility, including peptides aimed at treating lung-related diseases. Full article
Show Figures

Figure 1