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Biopolymers in Drug and Gene Delivery Systems 3.0

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

Deadline for manuscript submissions: 20 May 2024 | Viewed by 4103

Special Issue Editor


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 and 2nd editions, we would like to add more results and new insights from recent research projects. You can find the 1st and 2nd editions at the following link.

https://www.mdpi.com/journal/ijms/special_issues/Biopolymers_Drug_Gene_Delivery_Systems
https://www.mdpi.com/journal/ijms/special_issues/Biopolymers_Delivery_Systems2

Dr. Yury A. Skorik
Guest Editor

Manuscript Submission Information

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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.

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Keywords

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

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Published Papers (4 papers)

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Research

29 pages, 6372 KiB  
Article
Serum-Resistant Ternary DNA Polyplexes for Suicide Gene Therapy of Uterine Leiomyoma
by Anna Egorova, Sofia Shtykalova, Marianna Maretina, Svetlana Freund, Alexander Selutin, Natalia Shved, Sergei Selkov and Anton Kiselev
Int. J. Mol. Sci. 2024, 25(1), 34; https://doi.org/10.3390/ijms25010034 - 19 Dec 2023
Viewed by 744
Abstract
Uterine leiomyoma (UL) is a prevalent benign tumor in women that frequently gives rise to a multitude of reproductive complications. The use of suicide gene therapy has been proposed as a highly promising method for treating UL. To achieve successful gene therapy, it [...] Read more.
Uterine leiomyoma (UL) is a prevalent benign tumor in women that frequently gives rise to a multitude of reproductive complications. The use of suicide gene therapy has been proposed as a highly promising method for treating UL. To achieve successful gene therapy, it is essential to develop carriers that can efficiently transport nucleic acids into targeted cells and tissues. The instability of polyplexes in blood and other biological fluids is a crucial factor to consider when using non-viral carriers. In this study, we present serum-resistant and cRGD-modified DNA complexes for targeted delivery genes to UL cells. Ternary polyplexes were formed by incorporating cystine-cross-linked polyglutamic acid modified with histidine residues. We employed two techniques in the production of cross-linked polyanionic coating: matrix polymerization and oxidative polycondensation. In this study, we investigated the physicochemical properties of ternary DNA complexes, including the size and zeta-potential of the nanoparticles. Additionally, we evaluated cellular uptake, toxicity levels, transfection efficiency and specificity in vitro. The study involved introducing the HSV-TK gene into primary UL cells as a form of suicide gene therapy modeling. We have effectively employed ternary peptide-based complexes for gene delivery into the UL organtypic model. By implementing in situ suicide gene therapy, the increase in apoptosis genes expression was detected, providing conclusive evidence of apoptosis occurring in the transfected UL tissues. The results of the study strongly suggest that the developed ternary polyplexes show potential as a valuable tool in the implementation of suicide gene therapy for UL. Full article
(This article belongs to the Special Issue Biopolymers in Drug and Gene Delivery Systems 3.0)
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23 pages, 10930 KiB  
Article
Polycondensed Peptide-Based Polymers for Targeted Delivery of Anti-Angiogenic siRNA to Treat Endometriosis
by Anna Egorova, Marianna Maretina, Iuliia Krylova and Anton Kiselev
Int. J. Mol. Sci. 2024, 25(1), 13; https://doi.org/10.3390/ijms25010013 - 19 Dec 2023
Viewed by 762
Abstract
Endometriosis (EM) is a prevalent gynecological disease characterized by the abnormal growth of tissue similar to the endometrium outside of the uterus. This condition is accompanied by the development of new blood vessels in endometriotic lesions. While surgical intervention is effective in removing [...] Read more.
Endometriosis (EM) is a prevalent gynecological disease characterized by the abnormal growth of tissue similar to the endometrium outside of the uterus. This condition is accompanied by the development of new blood vessels in endometriotic lesions. While surgical intervention is effective in removing endometriotic lesions, some patients require multiple surgeries. Therefore, finding non-surgical treatments for EM is of great interest. One of the promising approaches is anti-angiogenic therapy using siRNA-therapeutics to target the expression of the VEGFA gene. Peptide-based polymers have shown promise as siRNA delivery systems due to their biocompatibility and ease of modification. We conducted a study to evaluate the effectiveness of the R6p-cRGD peptide carrier as a non-viral vehicle for delivering siRNA to endothelial cells in vitro and endometrial implants in vivo. We investigated the physicochemical properties of the siRNA-complexes, assessed cellular toxicity, and examined the efficiency of GFP and VEGFA genes silencing. Furthermore, we tested the anti-angiogenic effects of these complexes in cellular and animal models. The transfection with siRNA complexes led to a significant increase in VEGFA gene knockdown efficiency and a decrease in the migration of endothelial cells. For the animal model, we induced endometriosis in rats by transplanting endometrial tissue subcutaneously. We evaluated the efficiency of anti-angiogenic therapy for EM in vivo using anti-VEGF siRNA/R6p-RGD complexes. During this assessment, we measured the volume of the implants, analyzed VEGFA gene expression, and conducted CD34 immunohistochemical staining. The results showed a significant decrease in the growth of endometriotic implants and in VEGFA gene expression. Overall, our findings demonstrate the potential of the R6p-cRGD peptide carrier as a delivery system for anti-angiogenic therapy of EM. Full article
(This article belongs to the Special Issue Biopolymers in Drug and Gene Delivery Systems 3.0)
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20 pages, 2835 KiB  
Article
Characteristics of Interpolyelectrolyte Complexes Based on Different Types of Pectin with Eudragit® EPO as Novel Carriers for Colon-Specific Drug Delivery
by Shamil F. Nasibullin, Julia V. Dunaeva, Lilija A. Akramova, Venera R. Timergalieva and Rouslan I. Moustafine
Int. J. Mol. Sci. 2023, 24(24), 17622; https://doi.org/10.3390/ijms242417622 - 18 Dec 2023
Viewed by 662
Abstract
Given that pectin is a well-known substance used for drug delivery, we aimed to obtain and further examine the efficacy of interpolyelectrolyte complexes based on citrus or apple pectin and the Eudragit® EPO for using these carriers in oral drug delivery. To [...] Read more.
Given that pectin is a well-known substance used for drug delivery, we aimed to obtain and further examine the efficacy of interpolyelectrolyte complexes based on citrus or apple pectin and the Eudragit® EPO for using these carriers in oral drug delivery. To characterize the physicochemical properties of these compounds, turbidity, gravimetry, viscosity, elementary analysis, FTIR spectroscopy, and DSC analysis were utilized. Diffusion transport characteristics were evaluated to assess the swelling ability of the matrices and the release of diclofenac sodium. To examine the release parameters, mathematical modeling was performed by using the Korsmayer–Peppas and Logistic equations as well. During the turbidity study, stoichiometry compositions were selected for the developed IPECs EPO/PecA and EPO/PecC at pH values = 4.0, 5.0, 6.0, and 7.0. The FTIR spectra of the complexes were characterized by an increase in the intensity of the bands at 1610 cm−1 and 1400 cm−1. According to the DSC analysis, IPEC has a certain Tg = 57.3 °C. The highest release rates were obtained for IPEC EPO/PecC_1 and EPO/PecC_4. The mechanism of drug transport from the matrices IPEC EPO/PecC, IPEC EPO/PecA_3, and EPO/PecA_4 can be characterized as Super Case II. Anomalous release (non-Fickian release) is typical for IPEC EPO/PecA_1 and EPO/PecA_2. Thus, the resulting systems can be further used for the effective delivery of the drugs to the colon. Full article
(This article belongs to the Special Issue Biopolymers in Drug and Gene Delivery Systems 3.0)
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16 pages, 3583 KiB  
Article
Cyanocobalamin-Modified Colistin–Hyaluronan Conjugates: Synthesis and Bioactivity
by Natallia V. Dubashynskaya, Anton N. Bokatyi, Tatiana S. Sall, Tatiana S. Egorova, Yuliya A. Nashchekina, Yaroslav A. Dubrovskii, Ekaterina A. Murashko, Elena N. Vlasova, Elena V. Demyanova and Yury A. Skorik
Int. J. Mol. Sci. 2023, 24(14), 11550; https://doi.org/10.3390/ijms241411550 - 17 Jul 2023
Cited by 3 | Viewed by 1506
Abstract
Polymeric drug delivery systems enhance the biopharmaceutical properties of antibiotics by increasing their bioavailability, providing programmable and controlled-release properties, and reducing toxicity. In addition, drug delivery systems are a promising strategy to improve the intestinal permeability of various antimicrobial agents, including colistin (CT). [...] Read more.
Polymeric drug delivery systems enhance the biopharmaceutical properties of antibiotics by increasing their bioavailability, providing programmable and controlled-release properties, and reducing toxicity. In addition, drug delivery systems are a promising strategy to improve the intestinal permeability of various antimicrobial agents, including colistin (CT). This study describes the modification of conjugates based on CT and hyaluronic acid (HA) with cyanocobalamin (vitamin B12). Vitamin B12 was chosen as a targeting ligand because it has its own absorption pathway in the small intestine. The resulting polysaccharide conjugates contained 95 μg/mg vitamin B12 and the CT content was 335 μg/mg; they consisted of particles of two sizes, 98 and 702 nm, with a ζ-potential of approximately −25 mV. An in vitro release test at pH 7.4 and pH 5.2 showed an ultra-slow release of colistin of approximately 1% after 10 h. The modified B12 conjugates retained their antimicrobial activity at the level of pure CT (minimum inhibitory concentration was 2 μg/mL). The resulting delivery systems also reduced the nephrotoxicity of CT by 30–40% (HEK 293 cell line). In addition, the modification of B12 improved the intestinal permeability of CT, and the apparent permeability coefficient of HA–CT–B12 conjugates was 3.5 × 10−6 cm/s, corresponding to an in vivo intestinal absorption of 50–100%. Thus, vitamin-B12-modified conjugates based on CT and HA may be promising oral delivery systems with improved biopharmaceutical properties. Full article
(This article belongs to the Special Issue Biopolymers in Drug and Gene Delivery Systems 3.0)
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