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

Deadline for manuscript submissions: closed (10 April 2023) | Viewed by 8428

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Special Issue Editor

Dr. Dashevskiy Andriy

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Guest Editor

Pharmaceutical Technology Department, Freie Universität Berlin, 12169 Berlin, Germany
Interests: functional polymers; coating; hot melt extrusion; biodegradable polymers

Special Issue Information

Dear Colleagues,

Significant progress in pharmaceutical technology over last decades would be unimaginable without wide application of polymers having special properties and functions. The polymers differ in origin—natural, semi- or synthetic as well as in functionality—dissolution retardation or solubility improvement, insurance of preparation processes or imparting required physical properties to the dosage form (e.g. rheological), improving the stability of active ingredients or biopharmaceutical characteristics (e.g. enteric or gastro-retentive dosage form). The variety of polymers is ranged from water-soluble/swellable pH in-/dependent to water-insoluble. A special group of polymers are biodegradable polymers increasingly used for parenteral dosage forms to prolong the drug release over weeks or months. Besides numerous advantages, there are still challenges associated, sometimes, with high costs, not sufficient standardization, or negative impact on the body (e.g. acidic environment on injection site).

In this insight, research papers investigating various aspects of polymer application in drug delivery would be appreciated.

Dr. Dashevskiy Andriy
Guest Editor

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Keywords

functional polymers
coating
hot melt extrusion
biodegradable polymers
swellable polymers
matrix tablets
microparticles (pellets)
drug release
poorly soluble drug
solubility improvement
drug targeting
drug delivery systems

Published Papers (7 papers)

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Research

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Open AccessArticle

Cyclodextrins and Their Polymers Affect Human Serum Albumin’s Interaction with Drugs Used in the Treatment of Pulmonary Infections

Natalya G. Belogurova

and

Elena V. Kudryashova

Pharmaceutics 2023, 15(6), 1598; https://doi.org/10.3390/pharmaceutics15061598 - 25 May 2023

Viewed by 429

Abstract

Respiratory infectious diseases have challenged medical communities and researchers. Ceftriaxone, meropenem and levofloxacin are widely used for bacterial infection treatment, although they possess severe side effects. To overcome this, we propose cyclodextrin (CD) and CD-based polymers as a drug delivery system for the drugs under consideration. CD polymers demonstrate higher binding affinity for levofloxacin (Ka ≈ 10⁵ M) compared to drug–CD complexes. CDs slightly alter the drugs’ affinity for human serum albumin (HSA), whereas CD polymers increase the drugs’ binding affinity up to 100 times. The most significant effect was observed for more the hydrophilic drugs ceftriaxone and meropenem. The drug’s encapsulation in CD carriers leads to a decrease in the degree of change in the protein’s secondary structure. The drug–CD carrier–HSA complexes demonstrate satisfying antibacterial activity in vitro, and even a high binding affinity does not decrease the drug’s microbiological properties after 24 h. The proposed carriers are promising for a drug form with a prolonged drug release. Full article

(This article belongs to the Special Issue Functional Polymers in Drug Delivery)

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Open AccessArticle

Thermoreversible Gels Based on Chitosan Copolymers as “Intelligent” Drug Delivery System with Prolonged Action for Intramuscular Injection

Igor D. Zlotnikov

Stanislav M. Malashkeevich

Natalia G. Belogurova

and

Elena V. Kudryashova

Pharmaceutics 2023, 15(5), 1478; https://doi.org/10.3390/pharmaceutics15051478 - 12 May 2023

Viewed by 477

Abstract

Thermosensitive gels based on copolymers (PEG–chitosan, chitosan–polyethylenimine, chitosan–arginine and glycol–chitosan–spermine) are presented as promising polycations for the formation of DNA polyplexes and the potential for the development of drugs with prolonged release (up to 30 days). Being in liquid form at room temperature, such compounds can be injected into muscle tissue with rapid gel formation at human body temperature. An intramuscular depot is formed with a therapeutic agent that provides a gradual release of the drug, such as an antibacterial or cytostatic. The physico-chemical parameters of the formation of polyplexes between polycationic polymers of various compositions and molecular architecture and DNA were studied via FTIR, UV-vis and fluorescence spectroscopy using the dyes rhodamine 6G (R6G) and acridine orange (AO). The competitive displacement of AO from AO-DNA complexes showed that, with a ratio of N/P = 1, most of the DNA is bound to a polycation. During the formation of polyplexes, the DNA charge is neutralized by a polycation, which is reflected in electrophoretic immobility. The cationic polymers described in this work at a concentration of 1–4% are capable of forming gels, and the thermoreversible property is most characteristic of pegylated chitosan. BSA, as a model anionic molecule, is released by half in 5 days from the Chit5-PEG5 gel; full release is achieved in 18–20 days. At the same time, in 5 days, the gel is destroyed up to 30%, and in 20 days, by 90% (release of chitosan particles). For the first time, flow cytometry was used to study DNA polyplexes, which showed the existence of fluorescent particles in a much larger number in combination with free DNA. Thus, functional stimulus-sensitive polymers are potentially applicable for the creation of prolonged therapeutic formulations for gene delivery systems, which were obtained. The revealed regularities appear to be a platform for the design of polyplexes with controllable stability, in particular, fulfilling the requirements imposed for gene delivery vehicles. Full article

(This article belongs to the Special Issue Functional Polymers in Drug Delivery)

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Open AccessArticle

Biomimetic Silica Particles with Self-Loading BMP-2 Knuckle Epitope Peptide and Its Delivery for Bone Regeneration

and

Pharmaceutics 2023, 15(4), 1061; https://doi.org/10.3390/pharmaceutics15041061 - 25 Mar 2023

Viewed by 730

Abstract

Biomimetic silica deposition is an in-situ immobilization method for bioactive molecules under biocompatible conditions. The osteoinductive P4 peptide derived from the knuckle epitope of bone morphogenetic protein (BMP), which binds to BMP receptor-II (BMPRII), has been newly found to contain silica formation ability. We found that the two lysine residues at the N-terminus of P4 played a vital role in silica deposition. The P4 peptide co-precipitated with silica during P4-mediated silicification, yielding P4/silica hybrid particles (P4@Si) with a high loading efficiency of 87%. P4 was released from P4@Si at a constant rate for over 250 h, representing a zero-order kinetic model. In flow cytometric analysis, P4@Si showed a 1.5-fold increase in the delivery capacity to MC3T3 E1 cells than the free form of P4. Furthermore, P4 was found anchored to hydroxyapatite (HA) through a hexa-glutamate tag, followed by P4-mediated silicification, yielding P4@Si coated HA. This suggested a superior osteoinductive potential compared to silica or P4 alone coated HA in the in vitro study. In conclusion, the co-delivery of the osteoinductive P4 peptide and silica by P4-mediated silica deposition is an efficient method for capturing and delivering its molecules and inducing synergistic osteogenesis. Full article

(This article belongs to the Special Issue Functional Polymers in Drug Delivery)

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Open AccessArticle

Chitosan Nanoparticles Loaded Poloxamer 407 Gel for Transungual Delivery of Terbinafine HCl

and

Pharmaceutics 2022, 14(11), 2353; https://doi.org/10.3390/pharmaceutics14112353 - 31 Oct 2022

Cited by 2 | Viewed by 1109

Abstract

The current study aimed to develop chitosan nanoparticles (CSNP) loaded poloxamer 407 (P407) gel formulation for transungual delivery of terbinafine HCl (TBN). TBN-CSNP were prepared by nanoprecipitation method and optimized by face-centered central composite design (FCCCD). Optimized TBN-CSNP formulation exhibited a spherical shape with hydrodynamic diameter; zeta potential and entrapment efficiency (EE) of 229 ± 5 nm; 37 ± 1.5 mV; and 75 ± 2% respectively. The solid state of TBN and its compatibility with formulation ingredients were confirmed through XRD and FTIR analysis respectively. TBN-CSNP loaded P407 gel exhibited pseudoplastic rheological behavior having a spreadability of 11 ± 2 g·cm/s. The washability study showed that 40 ± 2% of the gel was eroded after washing 12 times. Drug release from TBN-CSNP- and TBN-CSNP-loaded gel was 84 ± 5% and 57 ± 3%, respectively. The cumulative quantity of TBN permeated from TBN-CSNP-loaded P407 gel and TBN-loaded P407 gel was 25 ± 8 and 27 ± 4 µg/cm², respectively. The nail uptake study showed that 3.6 ± 0.7 and 2.1 ± 0.3 µg of rhodamine was uptaken by the nail following 2 h topical application of TBN-CSNP loaded P407 gel and TBN loaded P407 gel, respectively. Hence, the developed CSNP-based P407 gel formulation can be a potential carrier for transungual delivery of TBN to topically treat onychomycosis. Full article

(This article belongs to the Special Issue Functional Polymers in Drug Delivery)

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Review

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Open AccessReview

Orodispersible Films—Current State of the Art, Limitations, Advances and Future Perspectives

Jan Ferlak

Weronika Guzenda

and

Tomasz Osmałek

Pharmaceutics 2023, 15(2), 361; https://doi.org/10.3390/pharmaceutics15020361 - 20 Jan 2023

Viewed by 1102

Abstract

Orodispersible Films (ODFs) are drug delivery systems manufactured with a wide range of methods on a big scale or for customized medicines and small-scale pharmacy. Both ODFs and their fabrication methods have certain limitations. Many pharmaceutical companies and academic research centers across the world cooperate in order to cope with these issues and also to find new formulations for a wide array of APIs what could make their work profitable for them and beneficial for patients as well. The number of pending patent applications and granted patents with their innovative approaches makes the progress in the manufacturing of ODFs unquestionable. The number of commercially available ODFs is still growing. However, some of them were discontinued and are no longer available on the markets. This review aims to summarize currently marketed ODFs and those withdrawn from sale and also provides an insight into recently published studies concerning orodispersible films, emphasizing of utilized APIs. The work also highlights the attempts of scientific communities to overcome ODF’s manufacturing methods limitations. Full article

(This article belongs to the Special Issue Functional Polymers in Drug Delivery)

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Open AccessReview

Polymeric Nanosystems Applied for Metal-Based Drugs and Photosensitizers Delivery: The State of the Art and Recent Advancements

Kele Cristina Ferreira Dantas

Jânia dos Santos Rosário

and

Priscila Pereira Silva-Caldeira

Pharmaceutics 2022, 14(7), 1506; https://doi.org/10.3390/pharmaceutics14071506 - 20 Jul 2022

Cited by 4 | Viewed by 1762

Abstract

Nanotechnology-based approaches for targeting the delivery and controlled release of metal-based therapeutic agents have revealed significant potential as tools for enhancing the therapeutic effect of metal-based agents and minimizing their systemic toxicities. In this context, a series of polymer-based nanosized systems designed to physically load or covalently conjugate metal-based therapeutic agents have been remarkably improving their bioavailability and anticancer efficacy. Initially, the polymeric nanocarriers were applied for platinum-based chemotherapeutic agents resulting in some nanoformulations currently in clinical tests and even in medical applications. At present, these nanoassemblies have been slowly expanding for nonplatinum-containing metal-based chemotherapeutic agents. Interestingly, for metal-based photosensitizers (PS) applied in photodynamic therapy (PDT), especially for cancer treatment, strategies employing polymeric nanocarriers have been investigated for almost 30 years. In this review, we address the polymeric nanocarrier-assisted metal-based therapeutics agent delivery systems with a specific focus on non-platinum systems; we explore some biological and physicochemical aspects of the polymer–metallodrug assembly. Finally, we summarize some recent advances in polymeric nanosystems coupled with metal-based compounds that present potential for successful clinical applications as chemotherapeutic or photosensitizing agents. We hope this review can provide a fertile ground for the innovative design of polymeric nanosystems for targeting the delivery and controlled release of metal-containing therapeutic agents. Full article

(This article belongs to the Special Issue Functional Polymers in Drug Delivery)

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Open AccessReview

Inhaled siRNA Formulations for Respiratory Diseases: From Basic Research to Clinical Application

Yulin Fan

and

Zhijun Yang

Pharmaceutics 2022, 14(6), 1193; https://doi.org/10.3390/pharmaceutics14061193 - 02 Jun 2022

Cited by 1 | Viewed by 2234

Abstract

The development of siRNA technology has provided new opportunities for gene-specific inhibition and knockdown, as well as new ideas for the treatment of disease. Four siRNA drugs have already been approved for marketing. However, the instability of siRNA in vivo makes systemic delivery ineffective. Inhaled siRNA formulations can deliver drugs directly to the lung, showing great potential for treating respiratory diseases. The clinical applications of inhaled siRNA formulations still face challenges because effective delivery of siRNA to the lung requires overcoming the pulmonary and cellular barriers. This paper reviews the research progress for siRNA inhalation formulations for the treatment of various respiratory diseases and summarizes the chemical structural modifications and the various delivery systems for siRNA. Finally, we conclude the latest clinical application research for inhaled siRNA formulations and discuss the potential difficulty in efficient clinical application. Full article

(This article belongs to the Special Issue Functional Polymers in Drug Delivery)

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