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Biopolymers in Drug and Gene Delivery Systems 2.0
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Biopolymers in Drug and Gene Delivery Systems 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Macromolecules".

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 19155

Special Issue Editor

Dr. Yury A. Skorik

E-Mail Website1 Website2
Guest Editor
1. Head of the Laboratory of Natural Polymers, Institute of Macromolecular Compounds of the Russian Academy of Sciences, St. Petersburg, Russia
2. Head of the Analytical Chemistry Department, Almazov National Medical Research Centre, St. Petersburg, Russia
Interests: polysaccharides; biomaterials; tissue engineering; drug delivery; gene delivery; nanomedicine; nanocomposites; electrospinning
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Biopolymers usually refer to natural polymers (mainly polysaccharides, proteins, and nucleic acids) produced by living organisms. In this Special Issue, this definition is extended to include semi-synthetic polymers (modified natural polymers) and synthetic polymers, which are biocompatible and biodegradable and can thus be used to design drug delivery systems. Natural and synthetic biopolymers each have advantages and disadvantages. While natural biopolymers are favored over synthetic polymers because of their biocompatibility, biodegradability, and environmental safety, synthetic biopolymers have distinct advantages regarding stability and can be adapted to suit a variety of biomedical applications.

This Special Issue invites authors from multidisciplinary fields to submit original research and up-to-date reviews on fundamental and applied aspects of the design, characterization, and properties of biopolymeric drug and gene delivery systems. Recent advances in polymer chemistry and technology have produced new functional biopolymers and smart nanomaterials with the potential to significantly improve the effectiveness of drug delivery. Ultimately, these materials could improve the treatment of severe diseases such as cancer, diabetes, and neurodegenerative and cardiovascular diseases. We hope that this Special Issue will contribute to the diffusion of new knowledge.

Due to the success of the 1st edition, we would like to add more results and new insights from recent research projects. You can find the 1st edition at the following link.

https://www.mdpi.com/journal/ijms/special_issues/Biopolymers_Drug_Gene_Delivery_Systems

Dr. Yury A. Skorik
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • biopolymers
  • drug delivery
  • gene delivery
  • biodegradable polymers
  • biocompatible polymers
  • nanomedicine

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Published Papers (10 papers)

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Editorial

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3 pages, 179 KiB  
Editorial
Biopolymers in Drug and Gene Delivery Systems 2.0
by Yury A. Skorik
Int. J. Mol. Sci. 2023, 24(23), 17099; https://doi.org/10.3390/ijms242317099 - 04 Dec 2023
Viewed by 771
Abstract
In recent years, significant progress has been made in the design and development of biopolymer-based delivery systems for a wide range of applications, including cancer therapy, gene editing, regenerative medicine, and vaccine delivery [...] Full article
(This article belongs to the Special Issue Biopolymers in Drug and Gene Delivery Systems 2.0)

Research

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24 pages, 3012 KiB  
Article
Synthesis and Characterization of Nanoparticle-Based Dexamethasone-Polypeptide Conjugates as Potential Intravitreal Delivery Systems
by Natalia Zashikhina, Sergei Gladnev, Vladimir Sharoyko, Viktor Korzhikov-Vlakh, Evgenia Korzhikova-Vlakh and Tatiana Tennikova
Int. J. Mol. Sci. 2023, 24(4), 3702; https://doi.org/10.3390/ijms24043702 - 12 Feb 2023
Cited by 4 | Viewed by 1712
Abstract
The use of dexamethasone for eye disease treatment is limited by its low solubility, bioavailability, and rapid elimination when applied topically. The covalent conjugation of dexamethasone with polymeric carriers is a promising strategy to overcome existing drawbacks. In this work, amphiphilic polypeptides capable [...] Read more.
The use of dexamethasone for eye disease treatment is limited by its low solubility, bioavailability, and rapid elimination when applied topically. The covalent conjugation of dexamethasone with polymeric carriers is a promising strategy to overcome existing drawbacks. In this work, amphiphilic polypeptides capable of self-assembly into nanoparticles were proposed as potential delivery systems for intravitreal delivery. The nanoparticles were prepared and characterized using poly(L-glutamic acid-co-D-phenylalanine) and poly(L-lysine-co-D/L-phenylalanine) as well as poly(L-lysine-co-D/L-phenylalanine) covered with heparin. The critical association concentration for the polypeptides obtained was in the 4.2–9.4 μg/mL range. The hydrodynamic size of the formed nanoparticles was between 90 and 210 nm, and they had an index of polydispersity between 0.08 and 0.27 and an absolute zeta-potential value between 20 and 45 mV. The ability of nanoparticles to migrate in the vitreous humor was examined using intact porcine vitreous. Conjugation of DEX with polypeptides was performed by additional succinylation of DEX and activation of carboxyl groups introduced to react with primary amines in polypeptides. The structures of all intermediate and final compounds were verified by 1H NMR spectroscopy. The amount of conjugated DEX can be varied from 6 to 220 µg/mg of polymer. The hydrodynamic diameter of the nanoparticle-based conjugates was increased to 200–370 nm, depending on the polymer sample and drug loading. The release of DEX from the conjugates due to hydrolysis of the ester bond between DEX and the succinyl moiety was studied both in a buffer medium and a vitreous/buffer mixture (50/50, v/v). As expected, the release in the vitreous medium was faster. However, the release rate could be controlled in the range of 96–192 h by varying the polymer composition. In addition, several mathematical models were used to assess the release profiles and figure out how DEX is released. Full article
(This article belongs to the Special Issue Biopolymers in Drug and Gene Delivery Systems 2.0)
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19 pages, 3635 KiB  
Article
Sulfonic Cryogels as Innovative Materials for Biotechnological Applications: Synthesis, Modification, and Biological Activity
by Svetlana Laishevkina, Tatiana Kuleshova, Gayane Panova, Elena Ivan’kova, Olga Iakobson, Anatoly Dobrodumov, Natalia Shevchenko and Alexander Yakimansky
Int. J. Mol. Sci. 2023, 24(3), 2949; https://doi.org/10.3390/ijms24032949 - 02 Feb 2023
Cited by 2 | Viewed by 1415
Abstract
Polymeric hydrogels based on sulfo-containing comonomers are promising materials for biotechnological application, namely, for use as a system for delivering water and minerals during seed germination in conditions of an unstable moisture zone. In this work, cryogels based on 3-sulfopropyl methacrylate and 2-hydroxyethyl [...] Read more.
Polymeric hydrogels based on sulfo-containing comonomers are promising materials for biotechnological application, namely, for use as a system for delivering water and minerals during seed germination in conditions of an unstable moisture zone. In this work, cryogels based on 3-sulfopropyl methacrylate and 2-hydroxyethyl methacrylate copolymers were obtained by the cryotropic gelation method. The morphology, specific surface area, and swelling behaviors of cryogels are found to depend on the total concentration of monomers in the reaction system and the content of the gel fraction in cryogels. Cryogels formed in the presence of nanodiamonds are shown to exhibit high biological activity during the germination of Lepidium sativum L. variety Ajur seeds, which manifests itself by stimulating seed germination and a significant increase in the raw weight of sprouts. These results indicate that sulfonic cryogels have a high potential to improve seed germination and plant growth, proving that such cryogels can be used as environmentally friendly materials for agricultural applications. Full article
(This article belongs to the Special Issue Biopolymers in Drug and Gene Delivery Systems 2.0)
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19 pages, 4782 KiB  
Article
Targeted Therapy for Glomerulonephritis Using Arterial Delivery of Encapsulated Etanercept
by Natalia A. Shushunova, Oksana A. Mayorova, Ekaterina S. Prikhozhdenko, Olga A. Goryacheva, Oleg A. Kulikov, Valentina O. Plastun, Olga I. Gusliakova, Albert R. Muslimov, Olga A. Inozemtseva, Nikolay A. Pyataev, Alexander A. Shirokov, Dmitry A. Gorin, Gleb B. Sukhorukov and Olga A. Sindeeva
Int. J. Mol. Sci. 2023, 24(3), 2784; https://doi.org/10.3390/ijms24032784 - 01 Feb 2023
Viewed by 1854
Abstract
Complex immunosuppressive therapy is prescribed in medical practice to patients with glomerulonephritis to help them overcome symptoms and prevent chronic renal failure. Such an approach requires long-term systemic administration of strong medications, which causes severe side effects. This work shows the efficiency of [...] Read more.
Complex immunosuppressive therapy is prescribed in medical practice to patients with glomerulonephritis to help them overcome symptoms and prevent chronic renal failure. Such an approach requires long-term systemic administration of strong medications, which causes severe side effects. This work shows the efficiency of polymer capsule accumulation (2.8 ± 0.4 µm) containing labeled etanercept (100 μg per dose) in the kidneys of mice. The comparison of injection into the renal artery and tail vein shows the significant superiority of the intra-arterial administration strategy. The etanercept retention rate of 18% and 8% ID in kidneys was found 1 min and 1 h after injection, respectively. The capsules were predominantly localized in the glomeruli after injection in mice using a model of acute glomerulonephritis. Histological analysis confirmed a significant therapeutic effect only in animals with intra-arterial administration of microcapsules with etanercept. The proposed strategy combines endovascular surgery and the use of polymer microcapsules containing a high molecular weight drug that can be successfully applied to treat a wide range of kidney diseases associated with glomerular pathology. Full article
(This article belongs to the Special Issue Biopolymers in Drug and Gene Delivery Systems 2.0)
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27 pages, 9418 KiB  
Article
Mannosylated Systems for Targeted Delivery of Antibacterial Drugs to Activated Macrophages
by Igor D. Zlotnikov, Maksim A. Vigovskiy, Maria P. Davydova, Milan R. Danilov, Uliana D. Dyachkova, Olga A. Grigorieva and Elena V. Kudryashova
Int. J. Mol. Sci. 2022, 23(24), 16144; https://doi.org/10.3390/ijms232416144 - 18 Dec 2022
Cited by 12 | Viewed by 2007
Abstract
Macrophages are a promising target for drug delivery to influence macrophage-associated processes in the body, namely due to the presence of resistant microorganisms in macrophages. In this work, a series of mannosylated carriers based on mannan, polyethylenimine (PEI) and cyclodextrin (CD) was synthesized. [...] Read more.
Macrophages are a promising target for drug delivery to influence macrophage-associated processes in the body, namely due to the presence of resistant microorganisms in macrophages. In this work, a series of mannosylated carriers based on mannan, polyethylenimine (PEI) and cyclodextrin (CD) was synthesized. The molecular architecture was studied using FTIR and 1H NMR spectroscopy. The particle size, from small 10–50 nm to large 500 nm, depending on the type of carrier, is potentially applicable for the creation of various medicinal forms: intravenous, oral and inhalation. Non-specific capture by cells with a simultaneous increase in selectivity to CD206+ macrophages was achieved. ConA was used as a model mannose receptor, binding galactosylated (CD206 non-specific) carriers with constants of the order of 104 M−1 and mannosylated conjugates of 106–107 M−1. The results of such primary “ConA-screening” of ligands are in a good agreement in terms of the comparative effectiveness of the interaction of ligands with the CD206+ macrophages: non-specific (up to 10%) absorption of highly charged and small particles; weakly specific uptake of galactosylated polymers (up to 50%); and high affine capture (more than 70–80%) of the ligands with grafted trimannoside was demonstrated using the cytometry method. Double and multi-complexes of antibacterials (moxifloxacin with its adjuvants from the class of terpenoids) were proposed as enhanced forms against resistant pathogens. In vivo pharmacokinetic experiments have shown that polymeric carriers significantly improve the efficiency of the antibiotic: the half-life of moxifloxacin is increased by 2–3 times in conjugate-loaded forms, bio-distribution to the lungs in the first hours after administration of the drug is noticeably greater, and, after 4 h of observation, free moxifloxacin was practically removed from the lungs of rats. Although, in polymer systems, its content is significant—1.2 µg/g. Moreover, the importance of the covalent crosslinking carrier with mannose label was demonstrated. Thus, this paper describes experimental, scientifically based methods of targeted drug delivery to macrophages to create enhanced medicinal forms. Full article
(This article belongs to the Special Issue Biopolymers in Drug and Gene Delivery Systems 2.0)
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15 pages, 1794 KiB  
Article
Antiherpetic Activity of Carrageenan Complex with Echinochrome A and Its Liposomal Form
by Natalia V. Krylova, Vladimir I. Gorbach, Olga V. Iunikhina, Anastasia B. Pott, Valery P. Glazunov, Anna O. Kravchenko, Mikhail Y. Shchelkanov and Irina M. Yermak
Int. J. Mol. Sci. 2022, 23(24), 15754; https://doi.org/10.3390/ijms232415754 - 12 Dec 2022
Cited by 2 | Viewed by 1393
Abstract
Herpes simplex virus (HSV) infections, the incidence of which is still widespread throughout the world, are actualizing the search and development of new, more effective antiherpetic drugs. The development of multifunctional drug delivery systems, including liposome-based ones, has become a relevant and attractive [...] Read more.
Herpes simplex virus (HSV) infections, the incidence of which is still widespread throughout the world, are actualizing the search and development of new, more effective antiherpetic drugs. The development of multifunctional drug delivery systems, including liposome-based ones, has become a relevant and attractive concept in nanotechnology. The ability of complexes of κ- and Σ-carrageenans (CRGs)—sulfated polysaccharides of red algae, with echinochrome A (Ech), as well as the liposomal form of the Σ-CRG/Ech complex—to inhibit different stages of HSV-1 infection in Vero cells was studied. By quantum chemical calculations, it was shown that CRG forms stable complexes with Ech. We have shown that complexes of κ-CRG/Ech and Σ-CRG/Ech exhibit highest virucidal activity with a selectivity index (SI) of 270 and 350, respectively, and inhibition of virus-cell interaction (SI of 83 and 32, respectively). The liposomal form of the Σ-CRG/Ech complex after virus adsorption and penetration to cells effectively reduced the HSV-1 plaque formation. The virus-inhibiting activity of the liposomal form of the Σ-CRG/Ech complex was three times higher than that of the Σ-CRG/Ech complex itself. Obtaining CRGs/Ech complexes and their liposomal forms can become the basis of a successful strategy for the development of promising antiherpetic drugs. Full article
(This article belongs to the Special Issue Biopolymers in Drug and Gene Delivery Systems 2.0)
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20 pages, 5491 KiB  
Article
Direct Cardiac Epigenetic Reprogramming through Codelivery of 5′Azacytidine and miR-133a Nanoformulation
by Priyadharshni Muniyandi, Vivekanandan Palaninathan, Tatsuro Hanajiri and Toru Maekawa
Int. J. Mol. Sci. 2022, 23(23), 15179; https://doi.org/10.3390/ijms232315179 - 02 Dec 2022
Cited by 3 | Viewed by 1688
Abstract
Direct reprogramming of cardiac fibroblasts to induced cardiomyocytes (iCMs) is a promising approach to cardiac regeneration. However, the low yield of reprogrammed cells and the underlying epigenetic barriers limit its potential. Epigenetic control of gene regulation is a primary factor in maintaining cellular [...] Read more.
Direct reprogramming of cardiac fibroblasts to induced cardiomyocytes (iCMs) is a promising approach to cardiac regeneration. However, the low yield of reprogrammed cells and the underlying epigenetic barriers limit its potential. Epigenetic control of gene regulation is a primary factor in maintaining cellular identities. For instance, DNA methylation controls cell differentiation in adults, establishing that epigenetic factors are crucial for sustaining altered gene expression patterns with subsequent rounds of cell division. This study attempts to demonstrate that 5′AZA and miR-133a encapsulated in PLGA-PEI nanocarriers induce direct epigenetic reprogramming of cardiac fibroblasts to cardiomyocyte-like cells. The results present a cardiomyocyte-like phenotype following seven days of the co-delivery of 5′AZA and miR-133a nanoformulation into human cardiac fibroblasts. Further evaluation of the global DNA methylation showed a decreased global 5-methylcytosine (5-medCyd) levels in the 5′AZA and 5′AZA/miR-133a treatment group compared to the untreated group and cells with void nanocarriers. These results suggest that the co-delivery of 5′AZA and miR-133a nanoformulation can induce the direct reprogramming of cardiac fibroblasts to cardiomyocyte-like cells in-vitro, in addition to demonstrating the influence of miR-133a and 5′AZA as epigenetic regulators in dictating cell fate. Full article
(This article belongs to the Special Issue Biopolymers in Drug and Gene Delivery Systems 2.0)
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17 pages, 4575 KiB  
Article
Altered Distribution and Expression of Syndecan-1 and -4 as an Additional Hallmark in Psoriasis
by Eleni Koliakou, Manthou Maria Eleni, Ioanna Koumentakou, Nikolaos Bikiaris, Polyanthi Konstantinidou, Patricia Rousselle, Doxakis Anestakis, Elisabeth Lazaridou, Evangelia Kalloniati, Dimosthenis Miliaras and Anna Michopoulou
Int. J. Mol. Sci. 2022, 23(12), 6511; https://doi.org/10.3390/ijms23126511 - 10 Jun 2022
Cited by 2 | Viewed by 2268
Abstract
Syndecans act as independent co-receptors to exert biological activities and their altered function is associated with many pathophysiological conditions. Here, syndecan-1 and -4 were examined in lesional skin of patients with psoriasis. Immunohistochemical staining confirmed altered syndecan-1 distribution and revealed absence of syndecan-4 [...] Read more.
Syndecans act as independent co-receptors to exert biological activities and their altered function is associated with many pathophysiological conditions. Here, syndecan-1 and -4 were examined in lesional skin of patients with psoriasis. Immunohistochemical staining confirmed altered syndecan-1 distribution and revealed absence of syndecan-4 expression in the epidermis. Fibronectin (FN)—known to influence inflammation and keratinocyte hyperproliferation via α5β1 integrin in psoriasis—was also decreased. Syndecan-1 and -4 expression was analyzed in freshly isolated lesional psoriatic human keratinocytes (PHK) characterized based on their proliferation and differentiation properties. mRNA levels of syndecan-1 were similar between healthy and PHK, while syndecan-4 was significantly decreased. Cell growth and release of the pro-inflammatory Tumor Necrosis Factor-alpha (TNFα) were selectively and significantly induced in PHKs plated on FN. Results from co-culture of healthy keratinocytes and psoriatic fibroblasts led to the speculation that at least one factor released by fibroblasts down-regulate syndecan-1 expression in PHK plated on FN. To assay if biological treatments for psoriasis target keratinocyte proliferation, gelatin-based patches enriched with inteleukin (IL)-17α or TNFα blockers were prepared and tested using a full-thickness healthy epidermal model (Phenion®). Immunohistochemistry analysis showed that both blockers impacted the localisation of syndecan-1 within the refined epidermis. These results provide evidence that syndecans expression are modified in psoriasis, suggesting that they may represent markers of interest in this pathology. Full article
(This article belongs to the Special Issue Biopolymers in Drug and Gene Delivery Systems 2.0)
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21 pages, 4416 KiB  
Article
Random Copolymers of Lysine and Isoleucine for Efficient mRNA Delivery
by Iuliia Pilipenko, Olga Korovkina, Nina Gubina, Viktoria Ekimova, Anastasia Ishutinova, Evgenia Korzhikova-Vlakh, Tatiana Tennikova and Viktor Korzhikov-Vlakh
Int. J. Mol. Sci. 2022, 23(10), 5363; https://doi.org/10.3390/ijms23105363 - 11 May 2022
Cited by 3 | Viewed by 2146
Abstract
Messenger RNA (mRNA) is currently of great interest as a new category of therapeutic agent, which could be used for prevention or treatment of various diseases. For this mRNA requires effective delivery systems that will protect it from degradation, as well as allow [...] Read more.
Messenger RNA (mRNA) is currently of great interest as a new category of therapeutic agent, which could be used for prevention or treatment of various diseases. For this mRNA requires effective delivery systems that will protect it from degradation, as well as allow cellular uptake and mRNA release. Random poly(lysine-co-isoleucine) polypeptides were synthesized and investigated as possible carriers for mRNA delivery. The polypeptides obtained under lysine:isoleucine monomer ratio equal to 80/20 were shown to give polyplexes with smaller size, positive ζ-potential and more than 90% encapsulation efficacy. The phase inversion method was proposed as best way for encapsulation of mRNA into polyplexes, which are based on obtained amphiphilic copolymers. These copolymers showed efficacy in protection of bound mRNA towards ribonuclease and lower toxicity as compared to lysine homopolymer. The poly(lysine-co-isoleucine) polypeptides showed greater than poly(ethyleneimine) efficacy as vectors for transfection of cells with green fluorescent protein and firefly luciferase encoding mRNAs. This allows us to consider obtained copolymers as promising candidates for mRNA delivery applications. Full article
(This article belongs to the Special Issue Biopolymers in Drug and Gene Delivery Systems 2.0)
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Review

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21 pages, 2415 KiB  
Review
Patches as Polymeric Systems for Improved Delivery of Topical Corticosteroids: Advances and Future Perspectives
by Natallia V. Dubashynskaya and Yury A. Skorik
Int. J. Mol. Sci. 2022, 23(21), 12980; https://doi.org/10.3390/ijms232112980 - 26 Oct 2022
Cited by 4 | Viewed by 2865
Abstract
Mucoadhesive polymer patches are a promising alternative for prolonged and controlled delivery of topical corticosteroids (CS) to improve their biopharmaceutical properties (mainly increasing local bioavailability and reducing systemic toxicity). The main biopharmaceutical advantages of patches compared to traditional oral dosage forms are their [...] Read more.
Mucoadhesive polymer patches are a promising alternative for prolonged and controlled delivery of topical corticosteroids (CS) to improve their biopharmaceutical properties (mainly increasing local bioavailability and reducing systemic toxicity). The main biopharmaceutical advantages of patches compared to traditional oral dosage forms are their excellent bioadhesive properties and their increased drug residence time, modified and unidirectional drug release, improved local bioavailability and safety profile, additional pain receptor protection, and patient friendliness. This review describes the main approaches that can be used for the pharmaceutical R&D of oromucosal patches with improved physicochemical, mechanical, and pharmacological properties. The review mainly focuses on ways to increase the bioadhesion of oromucosal patches and to modify drug release, as well as ways to improve local bioavailability and safety by developing unidirectional -release poly-layer patches. Various techniques for obtaining patches and their influence on the structure and properties of the resulting dosage forms are also presented. Full article
(This article belongs to the Special Issue Biopolymers in Drug and Gene Delivery Systems 2.0)
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