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Pharmaceutics
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Advanced Polymeric-Based Nanocarriers for Drug Delivery and Theranosis
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Advanced Polymeric-Based Nanocarriers for Drug Delivery and Theranosis

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Nanomedicine and Nanotechnology".

Deadline for manuscript submissions: closed (30 April 2021) | Viewed by 22688

Special Issue Editor

Prof. Dr. Pablo Taboada

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Guest Editor
Colloids and Polymer Physics Group (GFCP), Condensed Matter Physics Area, Faculty of Physics, Universidade de Santiago de Compostela, 15782 Campus Vida, Santiago de Compostela, Spain
Interests: nanomedicine; polymeric nanocarriers and scaffolds; organic and inorganic nanoparticles; drug delivery; bioimaging; theranosis; (bio)detection; tissue regeneration

Special Issue Information

Dear Colleagues,

In recent years, great efforts have been made in the biomedical field to design nano- and microcarriers based on polymeric micelles, vesicles, and nanoparticles that integrate in their structure and/or composition components that are responsive to well-focused triggering internal and external stimuli. These special features can be exploited for achieving enhanced contrast in bioimaging; to control the site, timing, and duration of release of bioactive molecules for therapeutic purposes; and/or the evaluation/monitoring of therapeutic efficacy, all in a remote, non-invasive, and reproducible manner.

Triggering mechanisms allowing obtaining the desired (bio)chemical and (bio)physical responses which can be induced by either interactions between a sensitive material forming the nanovehicle or the nanocarrier itself, and changes in its surrounding environment related to certain biochemicals or biophysical factors related, for example, to the progression of a disease (i.e., pH and temperature changes and/or the concentration of some (bio)chemical species) or by external stimuli (such as light, electric and magnetic fields, ultrasounds, etc.) whose duration and intensity can be controlled by an external operator.

The aim of this Special Issue of Pharmaceutics is to present novel research and review papers on new sensitive polymeric-based nanocarriers in the pharmaceutical and biomedical fields. We welcome articles dealing with all aspects of the synthesis, characterization and intended applications in drug delivery, bioimaging, therapeutics, and theranostics of stimuli-responsive polymeric-based nanoplatforms, and invite researchers to publish their original or review articles showcasing their expert opinions and perspectives in these areas.

Prof. Pablo Taboada
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • polymeric nanovehicles
  • sensitive polymer
  • stimulus
  • external/internal trigger
  • bioimaging
  • drug delivery
  • sustained release
  • therapy
  • theranostics
  • personalized medicine

Published Papers (7 papers)

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Research

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19 pages, 3459 KiB  
Article
Combined Therapeutics for Atherosclerosis Treatment Using Polymeric Nanovectors
by Baltazar Hiram Leal, Brenda Velasco, Adriana Cambón, Alberto Pardo, Javier Fernandez-Vega, Lilia Arellano, Abeer Al-Modlej, Víctor X. Mosquera, Alberto Bouzas, Gerardo Prieto, Silvia Barbosa and Pablo Taboada
Pharmaceutics 2022, 14(2), 258; https://doi.org/10.3390/pharmaceutics14020258 - 22 Jan 2022
Cited by 8 | Viewed by 2792
Abstract
Atherosclerosis is an underlying risk factor in cardiovascular diseases (CVDs). The combination of drugs with microRNAs (miRNA) inside a single nanocarrier has emerged as a promising anti-atherosclerosis strategy to achieve the exploitation of their complementary mechanisms of action to achieve synergistic therapeutic effects [...] Read more.
Atherosclerosis is an underlying risk factor in cardiovascular diseases (CVDs). The combination of drugs with microRNAs (miRNA) inside a single nanocarrier has emerged as a promising anti-atherosclerosis strategy to achieve the exploitation of their complementary mechanisms of action to achieve synergistic therapeutic effects while avoiding some of the drawbacks associated with current systemic statin therapies. We report the development of nanometer-sized polymeric PLGA nanoparticles (NPs) capable of simultaneously encapsulating and delivering miRNA-124a and the statin atorvastatin (ATOR). The polymeric NPs were functionalized with an antibody able to bind to the vascular adhesion molecule-1 (VCAM1) overexpressed in the inflamed arterial endothelium. The dual-loaded NPs were non-toxic to cells in a large range of concentrations, successfully attached overexpressed VCAM receptors and released the cargoes in a sustainable manner inside cells. The combination of both ATOR and miRNA drastically reduced the levels of proinflammatory cytokines such as IL-6 and TNF-α and of reactive oxygen species (ROS) in LPS-activated macrophages and vessel endothelial cells. In addition, dual-loaded NPs precluded the accumulation of low-density lipoproteins (LdL) inside macrophages as well as morphology changes to a greater extent than in single-loaded NPs. The reported findings validate the present NPs as suitable delivery vectors capable of simultaneously targeting inflamed cells in atherosclerosis and providing an efficient approach to combination nanomedicines. Full article
(This article belongs to the Special Issue Advanced Polymeric-Based Nanocarriers for Drug Delivery and Theranosis)
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12 pages, 1280 KiB  
Communication
Spontaneously Self-Assembled Microgel Film as Co-Delivery System for Skincare Applications
by Garbine Aguirre, Pablo Taboada and Laurent Billon
Pharmaceutics 2021, 13(9), 1422; https://doi.org/10.3390/pharmaceutics13091422 - 08 Sep 2021
Cited by 3 | Viewed by 1775
Abstract
Nowadays, the design of innovative delivery systems is driving new product developments in the field of skincare. In this regard, serving as potential candidates for on-demand drug delivery and fulfilling advanced mechanical and optical properties together with surface protection, spontaneously self-assembled microgel films [...] Read more.
Nowadays, the design of innovative delivery systems is driving new product developments in the field of skincare. In this regard, serving as potential candidates for on-demand drug delivery and fulfilling advanced mechanical and optical properties together with surface protection, spontaneously self-assembled microgel films can be proposed as ideal smart skincare systems. Currently, the high encapsulation of more than one drug simultaneously in a film is a very challenging task. Herein, different ratios (1:1, 3:1, 9:1) of different mixtures of hydrophilic/hydrophobic UVA/UVB-absorbers working together in synergy and used for skin protection were encapsulated efficiently into spontaneously self-assembled microgel films. In addition, in vitro release profiles show a controlled release of the different active molecules regulated by the pH and temperature of the medium. The analysis of the release mechanisms by the Peppas–Sahlin model indicated a superposition of diffusion-controlled and swelling-controlled releases. Finally, the distribution of active molecule mixtures into the film was studied by confocal Raman microscopy imaging corroborating the release profiles obtained. Full article
(This article belongs to the Special Issue Advanced Polymeric-Based Nanocarriers for Drug Delivery and Theranosis)
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18 pages, 4350 KiB  
Article
Infection Responsive Smart Delivery of Antibiotics Using Recombinant Spider Silk Nanospheres
by Pranothi Mulinti, Jacob Shreffler, Raquib Hasan, Michael Dea and Amanda E. Brooks
Pharmaceutics 2021, 13(9), 1358; https://doi.org/10.3390/pharmaceutics13091358 - 28 Aug 2021
Cited by 12 | Viewed by 3307
Abstract
Frequent and inappropriate usage of antibiotics has changed the natural evolution of bacteria by reducing susceptibility and increasing resistance towards antibacterial agents. New resistance mechanisms evolved in the response to host defenses and pharmaceutical interventions are threatening our ability to treat common infections, [...] Read more.
Frequent and inappropriate usage of antibiotics has changed the natural evolution of bacteria by reducing susceptibility and increasing resistance towards antibacterial agents. New resistance mechanisms evolved in the response to host defenses and pharmaceutical interventions are threatening our ability to treat common infections, resulting in increased mortality. In the face of this rising epidemic, antibiotic drug discovery, which has long been overlooked by big pharma, is reaching a critical low. Thus, the development of an infection-responsive drug delivery system, which may mitigate multidrug resistance and preserve the lifetime of our current antibiotic arsenal, has garnered the attention of both popular science and funding agencies. The present work describes the development of a thrombin-sensitive linker embedded into a recombinant spider silk copolymer to create a nanosphere drug delivery vehicle. Recent studies have suggested that there is an increase in thrombin-like activity during Staphylococcus aureus infection; thus, drug release from this new “smart” nanosphere can be triggered in the presence of infection. A thrombin sensitive peptide (TSP) was synthesized, and the thrombin cleavage sensitivity was determined by HPLC. The results showed no cleavage of the peptide when exposed to human serum whereas the peptide was cleaved when incubated with S. aureus exudate. Subsequently, the peptide was coupled with a silk copolymer via EDC-NHS chemistry and formulated into nanospheres encapsulating antibiotic vancomycin. These nanospheres were evaluated for in vitro infection-responsive drug release and antimicrobial activity. Finally, the drug responsive nanospheres were assessed for efficacy in an in vivo septic arthritis model. Our study provides evidence that the protein conjugate was enzyme responsive and can be used to formulate targeted drug release to combat infections against multidrug-resistant bacterial strains. Full article
(This article belongs to the Special Issue Advanced Polymeric-Based Nanocarriers for Drug Delivery and Theranosis)
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21 pages, 4628 KiB  
Article
Modulation of Inflammatory Mediators by Polymeric Nanoparticles Loaded with Anti-Inflammatory Drugs
by Gloria María Pontes-Quero, Lorena Benito-Garzón, Juan Pérez Cano, María Rosa Aguilar and Blanca Vázquez-Lasa
Pharmaceutics 2021, 13(2), 290; https://doi.org/10.3390/pharmaceutics13020290 - 23 Feb 2021
Cited by 20 | Viewed by 3212
Abstract
The first-line treatment of osteoarthritis is based on anti-inflammatory drugs, the most currently used being nonsteroidal anti-inflammatory drugs, selective cyclooxygenase 2 (COX-2) inhibitors and corticoids. Most of them present cytotoxicity and low bioavailability in physiological conditions, making necessary the administration of high drug [...] Read more.
The first-line treatment of osteoarthritis is based on anti-inflammatory drugs, the most currently used being nonsteroidal anti-inflammatory drugs, selective cyclooxygenase 2 (COX-2) inhibitors and corticoids. Most of them present cytotoxicity and low bioavailability in physiological conditions, making necessary the administration of high drug concentrations causing several side effects. The goal of this work was to encapsulate three hydrophobic anti-inflammatory drugs of different natures (celecoxib, tenoxicam and dexamethasone) into core-shell terpolymer nanoparticles with potential applications in osteoarthritis. Nanoparticles presented hydrodynamic diameters between 110 and 130 nm and almost neutral surface charges (between −1 and −5 mV). Encapsulation efficiencies were highly dependent on the loaded drug and its water solubility, having higher values for celecoxib (39–72%) followed by tenoxicam (20–24%) and dexamethasone (14–26%). Nanoencapsulation reduced celecoxib and dexamethasone cytotoxicity in human articular chondrocytes and murine RAW264.7 macrophages. Moreover, the three loaded systems did not show cytotoxic effects in a wide range of concentrations. Celecoxib and dexamethasone-loaded nanoparticles reduced the release of different inflammatory mediators (NO, TNF-α, IL-1β, IL-6, PGE2 and IL-10) by lipopolysaccharide (LPS)-stimulated RAW264.7. Tenoxicam-loaded nanoparticles reduced NO and PGE2 production, although an overexpression of IL-1β, IL-6 and IL-10 was observed. Finally, all nanoparticles proved to be biocompatible in a subcutaneous injection model in rats. These findings suggest that these loaded nanoparticles could be suitable candidates for the treatment of inflammatory processes associated with osteoarthritis due to their demonstrated in vitro activity as regulators of inflammatory mediator production. Full article
(This article belongs to the Special Issue Advanced Polymeric-Based Nanocarriers for Drug Delivery and Theranosis)
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18 pages, 3458 KiB  
Article
Effect of Dexamethasone-Loaded PLGA Nanoparticles on Oral Mucositis Induced by 5-Fluorouracil
by Susana Barbosa Ribeiro, Aurigena Antunes de Araújo, Maisie Mitchele Barbosa Oliveira, Alaine Maria dos Santos Silva, Arnóbio Antônio da Silva-Júnior, Gerlane Coelho Bernardo Guerra, Gerly Anne de Castro Brito, Renata Ferreira de Carvalho Leitão, Raimundo Fernandes de Araújo Júnior, Vinícius Barreto Garcia, Roseane Carvalho Vasconcelos and Caroline Addison Carvalho Xavier de Medeiros
Pharmaceutics 2021, 13(1), 53; https://doi.org/10.3390/pharmaceutics13010053 - 04 Jan 2021
Cited by 14 | Viewed by 2832
Abstract
Oral mucositis (OM) is characterized by the presence of severe ulcers in the oral region that affects patients treated with chemotherapy. It occurs in almost all patients who receive radiotherapy of the head and neck, as well as patients who undergo hematopoietic cell [...] Read more.
Oral mucositis (OM) is characterized by the presence of severe ulcers in the oral region that affects patients treated with chemotherapy. It occurs in almost all patients who receive radiotherapy of the head and neck, as well as patients who undergo hematopoietic cell transplantation. The pathophysiology of OM is complex, and there is no effective therapy. The aim of this study was to evaluate the effect of dexamethasone-loaded poly(d,l-Lactic-co-glycolic) nanoparticles (PLGA-DEX NPs) on an OM model induced in hamsters. The NPs were synthesized using the emulsification-solvent evaporation method and were characterized by the size, zeta potential, encapsulation efficiency, atomic force microscopy, physicochemical stability, and the in vitro release. The OM was induced by the administration of 5-FU on the first and second days and mechanical trauma on the 4th day of the experiment. PLGA-DEX NPs were administered to treat OM. The animals were euthanized on the 10th day. Macroscopic and histopathological analyses were performed, measurement of malonaldehyde (MDA) and ELISA was used to determine the levels of IL-1β and TNF-α. Immunoexpressions of NF-κB, COX-2, and TGF-β were determined by immunohistochemistry, and qRT-PCR was used to quantify the gene expression of the GILZ, MKP1, and NF-κB p65. The PLGA-DEX NPs (0.1 mg/kg) significantly reduced macroscopic and histopathological scores, decreased MDA, TNF-α and IL-1β levels, immunostaining for NF-κB, COX-2, TGF-β, and suppressed NF-κB p65 mRNA expression, but increased GILZ and MKP1 expression. Full article
(This article belongs to the Special Issue Advanced Polymeric-Based Nanocarriers for Drug Delivery and Theranosis)
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17 pages, 17756 KiB  
Article
pH-Sensitive Mixed Micelles Assembled from PDEAEMA-PPEGMA and PCL-PPEGMA for Doxorubicin Delivery: Experimental and DPD Simulations Study
by Chufen Yang, Wenyao Liu, Jiayu Xiao, Cong Yuan, Yaoxi Chen, Jianwei Guo, Hangbo Yue, Dongyu Zhu, Wenjing Lin, Shengqiu Tang and Xiaoying Dong
Pharmaceutics 2020, 12(2), 170; https://doi.org/10.3390/pharmaceutics12020170 - 18 Feb 2020
Cited by 17 | Viewed by 3707
Abstract
To decrease critical micelle concentration (CMC), improve stability, and keep high drug-loading capacity, three pH-sensitive mixed micelles applied for anticancer drug controlled delivery were prepared by the mixture of polymers poly (N,N-diethylaminoethyl methacrylate)-b-poly(poly(ethylene glycol) methyl ether methacrylate) (PDEAEMA-PPEGMA) and [...] Read more.
To decrease critical micelle concentration (CMC), improve stability, and keep high drug-loading capacity, three pH-sensitive mixed micelles applied for anticancer drug controlled delivery were prepared by the mixture of polymers poly (N,N-diethylaminoethyl methacrylate)-b-poly(poly(ethylene glycol) methyl ether methacrylate) (PDEAEMA-PPEGMA) and polycaprolactone-b-poly (poly(ethylene glycol) methyl ether methacrylate) (PCL-PPEGMA), which were synthesized and confirmed by 1H NMR and gel permeation chromatographic (GPC). The critical micelle concentration (CMC) values of the prepared mixed micelles were low, and the micellar sizes and zeta potentials of the blank mixed micelles demonstrated good pH-responsive behavior. Combined experimental techniques with dissipative particle dynamics (DPD) simulation, the particle sizes, zeta potentials, drug loading content (LC), encapsulation efficiency (EE), aggregation morphologies, and doxorubicin (DOX) distribution of the mixed micelles were investigated, and the high DOX-loading capacity of the mixed micelles was found. Both in vitro DOX release profiles and DPD simulations of the DOX dynamics release process exhibited less leakage and good stability in neutral conditions and accelerated drug release behavior with a little initial burst in slightly acidic conditions. Cytotoxicity tests showed that the polymer PDEAEMA-PPEGMA and the blank mixed micelles had good biocompatibility, and DOX-loaded mixed micelles revealed certain cytotoxicity. These results suggest that the drug-loaded mixed micelles that consisted of the two polymers PDEAEMA-PPEGMA and PCL-PPEGMA can be new types of pH-responsive well-controlled release anticancer drug delivery mixed micelles. Full article
(This article belongs to the Special Issue Advanced Polymeric-Based Nanocarriers for Drug Delivery and Theranosis)
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Review

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16 pages, 3520 KiB  
Review
Advantages and Disadvantages of Using Magnetic Nanoparticles for the Treatment of Complicated Ocular Disorders
by Elena K. Schneider-Futschik and Felisa Reyes-Ortega
Pharmaceutics 2021, 13(8), 1157; https://doi.org/10.3390/pharmaceutics13081157 - 27 Jul 2021
Cited by 30 | Viewed by 4306
Abstract
Nanomaterials provide enormous opportunities to overcome the limitations of conventional ocular delivery systems, such as low therapeutic efficacy, side effects due to the systemic exposure, or invasive surgery. Apart from the more common ocular disorders, there are some genetic diseases, such as cystic [...] Read more.
Nanomaterials provide enormous opportunities to overcome the limitations of conventional ocular delivery systems, such as low therapeutic efficacy, side effects due to the systemic exposure, or invasive surgery. Apart from the more common ocular disorders, there are some genetic diseases, such as cystic fibrosis, that develop ocular disorders as secondary effects as long as the disease progresses. These patients are more difficult to be pharmacologically treated using conventional drug routes (topically, systemic), since specific pharmacological formulations can be incompatible, display increased toxicity, or their therapeutic efficacy decreases with the administration of different kind of chemical molecules. Magnetic nanoparticles can be used as potent drug carriers and magnetic hyperthermia agents due to their response to an external magnetic field. Drugs can be concentrated in the target point, limiting the damage to other tissues. The other advantage of these magnetic nanoparticles is that they can act as magnetic resonance imaging agents, allowing the detection of the exact location of the disease. However, there are some drawbacks related to their use in drug delivery, such as the limitation to maintain efficacy in the target organ once the magnetic field is removed from outside. Another disadvantage is the difficulty in maintaining the therapeutic action in three dimensions inside the human body. This review summarizes all the application possibilities related to magnetic nanoparticles in ocular diseases. Full article
(This article belongs to the Special Issue Advanced Polymeric-Based Nanocarriers for Drug Delivery and Theranosis)
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