Synthetic Polymers for the Delivery of Vaccines and Therapeutics

A special issue of Journal of Functional Biomaterials (ISSN 2079-4983). This special issue belongs to the section "Biomaterials for Drug Delivery".

Deadline for manuscript submissions: closed (20 February 2024) | Viewed by 8541

Special Issue Editor

Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850, USA
Interests: stimuli-responsive synthetic macromolecules; nanoparticulate drug delivery systems; water-soluble biodegradable polymers; supramolecular self-assembly; polymer-protein interactions; immunoadjuvants and vaccine delivery systems; biofunctionalized coatings; non-covalent PEGylation; biocompatible polyphosphazenes

Special Issue Information

Dear Colleagues,

Synthetic polymers have been widely explored for life sciences applications, including those for the delivery of therapeutic drugs and vaccines. Although only a small fraction of these polymers are currently approved for human use (e.g., some polyesters and poly(ethylene glycols) (PEGs)), the quest for novel multifunctional materials to satisfy unmet medical needs continues.

The aim of this Special Issue is to provide a comprehensive overview of biodegradable synthetic macromolecules for the delivery of biotechnological drugs and preventive vaccines, the development of polymers for biological interfaces, drug-eluting coronary stents and medical implants, and biologically active polymer-based materials for tissue repair and regeneration. The topics include the synthesis of biodegradable and bioactive polymers, the stability of biomaterials and mechanisms of their hydrolytic or enzymatic degradation, advances in modulated drug release, polymer self-assembly and supramolecular architectures, PEG alternatives, nano-engineering of coatings and three-dimensional matrices, multifunctional systems with targeting capabilities, smart delivery vehicles and polymers for image-guided therapies.

Prof. Dr. Alexander K. Andrianov
Guest Editor

Manuscript Submission Information

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Keywords

  • biodegradable polymers
  • synthetic biocompatible materials
  • controlled drug release
  • macromolecular nano-assemblies
  • polymer biointerfaces
  • smart delivery systems
  • drug-eluting materials

Published Papers (6 papers)

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Research

12 pages, 2742 KiB  
Article
Polycarbonate-Based Copolymer Micelles as Biodegradable Carriers of Anticancer Podophyllotoxin or Juniper Extracts
by Radostina G. Kalinova, Ivaylo V. Dimitrov, Diana I. Ivanova, Yana E. Ilieva, Alexander N. Tashev, Maya M. Zaharieva, George Angelov and Hristo M. Najdenski
J. Funct. Biomater. 2024, 15(3), 53; https://doi.org/10.3390/jfb15030053 - 21 Feb 2024
Viewed by 858
Abstract
Podophyllotoxin (PPT) is used in the industrial production of efficient anticancer, antiviral and other drugs. Sinopodophyllum hexandrum or Podophyllum peltatum are natural sources of PPT, but at present they are considered as endangered species. Their PPT content is variable, depending on the growing [...] Read more.
Podophyllotoxin (PPT) is used in the industrial production of efficient anticancer, antiviral and other drugs. Sinopodophyllum hexandrum or Podophyllum peltatum are natural sources of PPT, but at present they are considered as endangered species. Their PPT content is variable, depending on the growing conditions. Searching for new sources of PPT, some representatives of the genus Juniperus were found to exhibit efficient PPT biosynthesis. However, PPT is highly toxic and poorly soluble in water compound, which limits its clinical applications. In this connection, amphiphilic polymer micelles are considered to be suitable PPT carriers, aimed at increase in water solubility and decrease in toxicity. The present research deals with the evaluation of MPEG–polycarbonate block copolymer micelles loaded with PPT or juniper extracts. The active component-loaded polymer nanocarriers were characterized by dynamic and electrophoretic light scattering, as well as by transmission electron microscopy. The active component loading efficiency and loading capacity were also determined. Highly efficient antiproliferative activity of the loaded micelles was determined in a panel of cancer cell lines. The obtained amphiphilic nanocarriers, loaded with PPT-containing bioactive components, have application in future in vivo preclinical trials of their pharmacokinetics and pharmacodynamics as potential therapeutical agents in the prospective nanomedicine. Full article
(This article belongs to the Special Issue Synthetic Polymers for the Delivery of Vaccines and Therapeutics)
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11 pages, 1386 KiB  
Article
Superfluorinated, Highly Water-Soluble Polyphosphazenes as Potential 19F Magnetic Resonance Imaging (MRI) Contrast Agents
by Paul Strasser, Verena Schinegger, Joachim Friske, Oliver Brüggemann, Thomas H. Helbich, Ian Teasdale and Irena Pashkunova-Martic
J. Funct. Biomater. 2024, 15(2), 40; https://doi.org/10.3390/jfb15020040 - 10 Feb 2024
Viewed by 807
Abstract
“Hot spot” 19F magnetic resonance imaging (MRI) has garnered significant attention recently for its ability to image various disease markers quantitatively. Unlike conventional gadolinium-based MRI contrast agents, which rely on proton signal modulation, 19F-MRI’s direct detection has a unique advantage in [...] Read more.
“Hot spot” 19F magnetic resonance imaging (MRI) has garnered significant attention recently for its ability to image various disease markers quantitatively. Unlike conventional gadolinium-based MRI contrast agents, which rely on proton signal modulation, 19F-MRI’s direct detection has a unique advantage in vivo, as the human body exhibits a negligible background 19F-signal. However, existing perfluorocarbon (PFC) or PFC-based contrast materials suffer from several limitations, including low longitudinal relaxation rates and relatively low imaging efficiency. Hence, we designed a macromolecular contrast agent featuring a high number of magnetically equivalent 19F-nuclei in a single macromolecule, adequate fluorine nucleus mobility, and excellent water solubility. This design utilizes superfluorinated polyphosphazene (PPz) polymers as the 19F-source; these are modified with sodium mercaptoethanesulfonate (MESNa) to achieve water solubility exceeding 360 mg/mL, which is a similar solubility to that of sodium chloride. We observed substantial signal enhancement in MRI with these novel macromolecular carriers compared to non-enhanced surroundings and aqueous trifluoroacetic acid (TFA) used as a positive control. In conclusion, these novel water-soluble macromolecular carriers represent a promising platform for future MRI contrast agents. Full article
(This article belongs to the Special Issue Synthetic Polymers for the Delivery of Vaccines and Therapeutics)
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16 pages, 2470 KiB  
Article
Role of the Lactide:Glycolide Ratio in PLGA Nanoparticle Stability and Release under Lysosomal Conditions for Enzyme Replacement Therapy of Lysosomal Storage Disorders
by Maria del Moral, Maximilian Loeck, Eameema Muntimadugu, Guillem Vives, Vy Pham, Peter Pfeifer, Giuseppe Battaglia and Silvia Muro
J. Funct. Biomater. 2023, 14(9), 440; https://doi.org/10.3390/jfb14090440 - 25 Aug 2023
Cited by 1 | Viewed by 1040
Abstract
Prior studies demonstrated that encapsulation in poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) enhanced the delivery of enzymes used for replacement therapy (ERT) of lysosomal storage disorders (LSDs). This study examined how the copolymer lactide:glycolide ratio impacts encapsulation, physicochemical characteristics, stability, and release under lysosomal [...] Read more.
Prior studies demonstrated that encapsulation in poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) enhanced the delivery of enzymes used for replacement therapy (ERT) of lysosomal storage disorders (LSDs). This study examined how the copolymer lactide:glycolide ratio impacts encapsulation, physicochemical characteristics, stability, and release under lysosomal conditions. Hyaluronidase, deficient in mucopolysaccharidosis IX, was encapsulated in NPs synthesized using 50:50, 60:40, or 75:25 lactide:glycolide copolymers. All NPs had diameters compatible with cellular transport (≤168 nm) and polydispersity indexes (≤0.16) and ζ-potentials (≤−35 mV) compatible with colloidal stability. Yet, their encapsulation efficiency varied, with 75:25 NPs and 60:40 NPs having the lowest and highest EE, respectively (15% vs. 28%). Under lysosomal conditions, the 50:50 copolymer degraded fastest (41% in 1 week), as expected, and the presence of a targeting antibody coat did not alter this result. Additionally, 60:40 NPs destabilized fastest (<1 week) because of their smaller diameter, and 75:25 NPs did not destabilize in 4 weeks. All formulations presented burst release under lysosomal conditions (56–78% of the original load within 30 min), with 50:50 and 60:40 NPs releasing an additional small fraction after week 1. This provided 4 weeks of sustained catalytic activity, sufficient to fully degrade a substrate. Altogether, the 60:40 NP formulation is preferred given its higher EE, and 50:50 NPs represent a valid alternative, while the highest stability of 75:25 NPs may impair lysosomes. These results can guide future studies aiming to translate PLGA NP-based ERT for this and other LSDs. Full article
(This article belongs to the Special Issue Synthetic Polymers for the Delivery of Vaccines and Therapeutics)
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14 pages, 2835 KiB  
Article
Investigation of the Real-Time Release of Doxycycline from PLA-Based Nanofibers
by Noémi-Izabella Farkas, Laura Marincaș, Lucian Barbu-Tudoran, Réka Barabás and Graziella Liana Turdean
J. Funct. Biomater. 2023, 14(6), 331; https://doi.org/10.3390/jfb14060331 - 20 Jun 2023
Cited by 2 | Viewed by 1107
Abstract
Electrospun mats of PLA and PLA/Hap nanofibers produced by electrospinning were loaded with doxycycline (Doxy) through physical adsorption from a solution with initial concentrations of 3 g/L, 7 g/L, and 12 g/L, respectively. The morphological characterization of the produced material was performed using [...] Read more.
Electrospun mats of PLA and PLA/Hap nanofibers produced by electrospinning were loaded with doxycycline (Doxy) through physical adsorption from a solution with initial concentrations of 3 g/L, 7 g/L, and 12 g/L, respectively. The morphological characterization of the produced material was performed using scanning electron microscopy (SEM). The release profiles of Doxy were studied in situ using the differential pulse voltammetry (DPV) electrochemical method on a glassy carbon electrode (GCE) and validated through UV-VIS spectrophotometric measurements. The DPV method has been shown to be a simple, rapid, and advantageous analytical technique for real-time measurements, allowing accurate kinetics to be established. The kinetics of the release profiles were compared using model-dependent and model-independent analyses. The diffusion-controlled mechanism of Doxy release from both types of fibers was confirmed by a good fit to the Korsmeyer–Peppas model. Full article
(This article belongs to the Special Issue Synthetic Polymers for the Delivery of Vaccines and Therapeutics)
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13 pages, 5004 KiB  
Article
Characterization of Cyclic Olefin Copolymers for Insulin Reservoir in an Artificial Pancreas
by Norma Mallegni, Mario Milazzo, Caterina Cristallini, Niccoletta Barbani, Giulia Fredi, Andrea Dorigato, Patrizia Cinelli and Serena Danti
J. Funct. Biomater. 2023, 14(3), 145; https://doi.org/10.3390/jfb14030145 - 04 Mar 2023
Cited by 1 | Viewed by 1588
Abstract
Type-1 diabetes is one of the most prevalent metabolic disorders worldwide. It results in a significant lack of insulin production by the pancreas and the ensuing hyperglycemia, which needs to be regulated through a tailored administration of insulin throughout the day. Recent studies [...] Read more.
Type-1 diabetes is one of the most prevalent metabolic disorders worldwide. It results in a significant lack of insulin production by the pancreas and the ensuing hyperglycemia, which needs to be regulated through a tailored administration of insulin throughout the day. Recent studies have shown great advancements in developing an implantable artificial pancreas. However, some improvements are still required, including the optimal biomaterials and technologies to produce the implantable insulin reservoir. Here, we discuss the employment of two types of cyclic olefin copolymers (Topas 5013L-10 and Topas 8007S-04) for an insulin reservoir fabrication. After a preliminary thermomechanical analysis, Topas 8007S-04 was selected as the best material to fabricate a 3D-printed insulin reservoir due to its higher strength and lower glass transition temperature (Tg). Fiber deposition modeling was used to manufacture a reservoir-like structure, which was employed to assess the ability of the material to prevent insulin aggregation. Although the surface texture presents a localized roughness, the ultraviolet analysis did not detect any significant insulin aggregation over a timeframe of 14 days. These interesting results make Topas 8007S-04 cyclic olefin copolymer a potential candidate biomaterial for fabricating structural components in an implantable artificial pancreas. Full article
(This article belongs to the Special Issue Synthetic Polymers for the Delivery of Vaccines and Therapeutics)
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15 pages, 1981 KiB  
Article
Skin Vaccination with Ebola Virus Glycoprotein Using a Polyphosphazene-Based Microneedle Patch Protects Mice against Lethal Challenge
by Andrey Romanyuk, Ruixue Wang, Alexander Marin, Benjamin M. Janus, Eric I. Felner, Dengning Xia, Yenny Goez-Gazi, Kendra J. Alfson, Abdul S. Yunus, Eric A. Toth, Gilad Ofek, Ricardo Carrion, Jr., Mark R. Prausnitz, Thomas R. Fuerst and Alexander K. Andrianov
J. Funct. Biomater. 2023, 14(1), 16; https://doi.org/10.3390/jfb14010016 - 27 Dec 2022
Cited by 7 | Viewed by 2578
Abstract
Ebolavirus (EBOV) infection in humans is a severe and often fatal disease, which demands effective interventional strategies for its prevention and treatment. The available vaccines, which are authorized under exceptional circumstances, use viral vector platforms and have serious disadvantages, such as difficulties in [...] Read more.
Ebolavirus (EBOV) infection in humans is a severe and often fatal disease, which demands effective interventional strategies for its prevention and treatment. The available vaccines, which are authorized under exceptional circumstances, use viral vector platforms and have serious disadvantages, such as difficulties in adapting to new virus variants, reliance on cold chain supply networks, and administration by hypodermic injection. Microneedle (MN) patches, which are made of an array of micron-scale, solid needles that painlessly penetrate into the upper layers of the skin and dissolve to deliver vaccines intradermally, simplify vaccination and can thereby increase vaccine access, especially in resource-constrained or emergency settings. The present study describes a novel MN technology, which combines EBOV glycoprotein (GP) antigen with a polyphosphazene-based immunoadjuvant and vaccine delivery system (poly[di(carboxylatophenoxy)phosphazene], PCPP). The protein-stabilizing effect of PCPP in the microfabrication process enabled preparation of a dissolvable EBOV GP MN patch vaccine with superior antigenicity compared to a non-polyphosphazene polymer-based analog. Intradermal immunization of mice with polyphosphazene-based MN patches induced strong, long-lasting antibody responses against EBOV GP, which was comparable to intramuscular injection. Moreover, mice vaccinated with the MN patches were completely protected against a lethal challenge using mouse-adapted EBOV and had no histologic lesions associated with ebolavirus disease. Full article
(This article belongs to the Special Issue Synthetic Polymers for the Delivery of Vaccines and Therapeutics)
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