Advances in Polymeric Drug Delivery Systems

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 30940

Special Issue Editors


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Guest Editor
Department of Chemistry, Faculty of Medicine in Zabrze, Academy of Silesia, 40-555 Katowice, Poland
Interests: biomaterials; biocompatibility of polymer systems; (bio)degradable and synthetic polymers in medical applications; degradation
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Special Issue Information

Dear Colleagues,

Research into the design, characterization, fabrication, and development of drug delivery systems used in pharmaceuticals based on natural and synthetic polymers has achieved tremendous growth over the past two decades. Efficient drug delivery systems are designed to improve the pharmacokinetics and pharmacodynamics of any therapy. Their goal is to enable the drug to be delivered to the right place, at the right time, and in the right amount. Drug delivery systems employ strategies such as controlled release, targeted delivery, or improving the solubility and stability of a drug in such a way so as to provide increased drug efficacy. The next step in effective drug delivery is to select a drug delivery system that can achieve the desired results.

The purpose of this Special Issue is to provide a contemporary overview of the latest developments in drug delivery systems, particularly breakthroughs and advances in the synthesis, fabrication, characterization, and applications of innovative polymeric biomaterials in drug delivery. The recently increasingly used (bio)degradable polymers are also noteworthy, as well as design and fabrication techniques, such as additive manufacturing, offering innovative possibilities for the design and development of systems with complex geometry, and programmed controlled release profile. Original research articles, case reports, letters, and short communications covering aspects of current trends in the development of such systems will be welcome.

Dr. Joanna Rydz
Dr. Barbara Zawidlak-Węgrzyńska
Guest Editors

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. 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

  • drug delivery
  • controlled release
  • biopolymers
  • nanopolymers
  • nanoparticles
  • (bio)degradable polymers
  • synthetic polymers
  • 3D printing
  • personalized medicine

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Published Papers (9 papers)

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Research

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18 pages, 4096 KiB  
Article
Co-Delivery of 8-Hydroxyquinoline Glycoconjugates and Doxorubicin by Supramolecular Hydrogel Based on α-Cyclodextrin and pH-Responsive Micelles for Enhanced Tumor Treatment
by Adrian Domiński, Tomasz Konieczny, Marcin Godzierz, Marta Musioł, Henryk Janeczek, Aleksander Foryś, Monika Domińska, Gabriela Pastuch-Gawołek, Tomasz Piotrowski and Piotr Kurcok
Pharmaceutics 2022, 14(11), 2490; https://doi.org/10.3390/pharmaceutics14112490 - 17 Nov 2022
Cited by 7 | Viewed by 2151
Abstract
The sustained release of multiple anti-cancer drugs using a single delivery carrier to achieve a synergistic antitumor effect remains challenging in biomaterials and pharmaceutics science. In this study, a supramolecular hydrogel based on the host–guest complexes between pH-responsive micelle derived poly(ethylene glycol) chains [...] Read more.
The sustained release of multiple anti-cancer drugs using a single delivery carrier to achieve a synergistic antitumor effect remains challenging in biomaterials and pharmaceutics science. In this study, a supramolecular hydrogel based on the host–guest complexes between pH-responsive micelle derived poly(ethylene glycol) chains and α-cyclodextrin was designed for codelivery of two kinds of anti-cancer agents, hydrophilic 8-hydroxyquinoline glycoconjugate and hydrophobic doxorubicin. The host–guest interactions were characterized using X-ray diffraction and differential scanning calorimetry techniques. The resultant supramolecular hydrogel showed thixotropic properties, which are advantageous to drug delivery systems. In vitro release studies revealed that the supramolecular hydrogel exhibited faster drug release profiles in acidic conditions. The MTT assay demonstrated a synergistic cancer cell proliferation inhibition of DOX/8HQ-Glu mixture. In vitro cytotoxicity studies indicated excellent biocompatibility of the supramolecular hydrogel matrix, whereas the DOX/8HQ-Glu-loaded supramolecular hydrogel showed a sustained inhibition efficacy against cancer cells. The codelivery of hydrophobic anti-cancer drugs and hydrophilic anti-cancer drug glycoconjugates via a pH-responsive supramolecular hydrogel opens up new possibilities for the development of an effective cancer treatment based on the tumor-specific Warburg effect. Full article
(This article belongs to the Special Issue Advances in Polymeric Drug Delivery Systems)
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16 pages, 5710 KiB  
Article
Effects of Drug Physicochemical Properties on In-Situ Forming Implant Polymer Degradation and Drug Release Kinetics
by Jordan B. Joiner, Alka Prasher, Isabella C. Young, Jessie Kim, Roopali Shrivastava, Panita Maturavongsadit and Soumya Rahima Benhabbour
Pharmaceutics 2022, 14(6), 1188; https://doi.org/10.3390/pharmaceutics14061188 - 1 Jun 2022
Cited by 16 | Viewed by 3013
Abstract
In-situ forming implants (ISFIs) represent a simple, tunable, and biodegradable polymer-based platform for long-acting drug delivery. However, drugs with different physicochemical properties and physical states in the polymer-solvent system exhibit different drug release kinetics. Although a few limited studies have been performed attempting [...] Read more.
In-situ forming implants (ISFIs) represent a simple, tunable, and biodegradable polymer-based platform for long-acting drug delivery. However, drugs with different physicochemical properties and physical states in the polymer-solvent system exhibit different drug release kinetics. Although a few limited studies have been performed attempting to elucidate these effects, a large, systematic study has not been performed until now. The purpose of this study was to characterize the in vitro drug release of 12 different small molecule drugs with differing logP and pKa values from ISFIs. Drug release was compared with polymer degradation as measured by lactic acid (LA) release and change in poly(DL-lactide-co-glycolide) (PLGA) molecular weight (MW) measured by size exclusion chromatography with multi-angle laser light scattering (SEC-MALS). Drug physical state and morphology were also measured using differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). Together, these results demonstrated that hydrophilic drugs have higher burst release at 24 h (22.8–68.4%) and complete drug release within 60 days, while hydrophobic drugs have lower burst release at 24 h (1.8–18.9%) and can sustain drug release over 60–285 days. Overall, drug logP and drug physical state in the polymer–solvent system are the most important factors when predicting the drug release rate in an ISFI for small-molecule drugs. Hydrophilic drugs exhibit high initial burst and less sustained release due to their miscibility with the aqueous phase, while hydrophobic drugs have lower initial burst and more sustained release due to their affinity for the hydrophobic PLGA. Additionally, while hydrophilic drugs seem to accelerate the degradation of PLGA, hydrophobic drugs on the other hand seem to slow down the PLGA degradation process compared with placebo ISFIs. Furthermore, drugs that were in a crystalline state within the ISFI drugs exhibited more sustained release compared with amorphous drugs. Full article
(This article belongs to the Special Issue Advances in Polymeric Drug Delivery Systems)
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10 pages, 7568 KiB  
Article
Dissolution from Ethylene Vinyl Acetate Copolymer Long-Acting Implants: Effect of Model Active Ingredient Size and Shape
by Anne M. Gohn, Amy Nolte, Ethan Ravotti, Seth P. Forster, Morgan Giles, Nathan Rudd and Gamini Mendis
Pharmaceutics 2022, 14(6), 1139; https://doi.org/10.3390/pharmaceutics14061139 - 27 May 2022
Viewed by 2205
Abstract
In recent pharmaceutical applications, an active pharmaceutical ingredient (API) can be mixed with a polymer material to yield a composite long-acting drug-delivery device. These devices boast higher patient compliance, localized drug delivery, and lower dosage concentrations, which can increase patient safety. As a [...] Read more.
In recent pharmaceutical applications, an active pharmaceutical ingredient (API) can be mixed with a polymer material to yield a composite long-acting drug-delivery device. These devices boast higher patient compliance, localized drug delivery, and lower dosage concentrations, which can increase patient safety. As a laboratory-safe option, calcium carbonate (CaCO3) was used as a drug surrogate to mimic the release kinetics of a low-solubility API. The release of CaCO3 from a poly(ethylene vinyl acetate) (EVA) polymer matrix was studied in ultra-high-purity water. The geometry of CaCO3, along with the manufacturing technique, was manipulated to study the implications on surrogate drug release. It was found that injection molding proved to yield higher burst release, due to higher pressures achievable during manufacturing. The extrusion process can affect the surface concentration of the pharmaceutical ingredient when extruded through a water bath, resulting in a lower initial burst concentration. Regarding CaCO3 geometry, the particle size was more critical than the surface area in terms of CaCO3 release. Larger particles showed a higher release rate, though they also displayed higher variability in release. These data can be used to engineer specific release profiles when designing composite formulations and manufacturing methods for pharmaceutical-drug-delivery applications. Full article
(This article belongs to the Special Issue Advances in Polymeric Drug Delivery Systems)
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Review

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18 pages, 1826 KiB  
Review
Polymer-Drug Anti-Thrombogenic and Hemocompatible Coatings as Surface Modifications
by Barbara Zawidlak-Węgrzyńska, Joanna Rydz, Marta Musioł and Aneta Radziwon-Balicka
Pharmaceutics 2024, 16(3), 432; https://doi.org/10.3390/pharmaceutics16030432 - 21 Mar 2024
Viewed by 1455
Abstract
Since the 1960s, efforts have been made to develop new technologies to eliminate the risk of thrombosis in medical devices that come into contact with blood. Preventing thrombosis resulting from the contact of a medical device, such as an implant, with blood is [...] Read more.
Since the 1960s, efforts have been made to develop new technologies to eliminate the risk of thrombosis in medical devices that come into contact with blood. Preventing thrombosis resulting from the contact of a medical device, such as an implant, with blood is a challenge due to the high mortality rate of patients and the high cost of medical care. To this end, various types of biomaterials coated with polymer-drug layers are being designed to reduce their thrombogenicity and improve their hemocompatibility. This review presents the latest developments in the use of polymer-drug systems to produce anti-thrombogenic surfaces in medical devices in contact with blood, such as stents, catheters, blood pumps, heart valves, artificial lungs, blood vessels, blood oxygenators, and various types of tubing (such as for hemodialysis) as well as microfluidic devices. This paper presents research directions and potential clinical applications, emphasizing the importance of continued progress and innovation in the field. Full article
(This article belongs to the Special Issue Advances in Polymeric Drug Delivery Systems)
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22 pages, 3915 KiB  
Review
Nanocellulose, the Green Biopolymer Trending in Pharmaceuticals: A Patent Review
by Keth Ribeiro Garcia, Ruy Carlos Ruver Beck, Rosmary Nichele Brandalise, Venina dos Santos and Letícia Scherer Koester
Pharmaceutics 2024, 16(1), 145; https://doi.org/10.3390/pharmaceutics16010145 - 21 Jan 2024
Viewed by 1635
Abstract
The use of nanocellulose in pharmaceutics is a trend that has emerged in recent years. Its inherently good mechanical properties, compared to different materials, such as its high tensile strength, high elastic modulus and high porosity, as well as its renewability and biodegradability [...] Read more.
The use of nanocellulose in pharmaceutics is a trend that has emerged in recent years. Its inherently good mechanical properties, compared to different materials, such as its high tensile strength, high elastic modulus and high porosity, as well as its renewability and biodegradability are driving nanocellulose’s industrial use and innovations. In this sense, this study aims to conduct a search of patents from 2011 to 2023, involving applications of nanocellulose in pharmaceuticals. A patent search was carried out, employing three different patent databases: Patentscope from World Intellectual Property Organization (WIPO); Espacenet; and LENS.ORG. Patents were separated into two main groups, (i) nanocellulose (NC) comprising all its variations and (ii) bacterial nanocellulose (BNC), and classified into five major areas, according to their application. A total of 215 documents was retrieved, of which 179 were referred to the NC group and 36 to the BNC group. The NC group depicted 49.7%, 15.6%, 16.2%, 8.9% and 9.5% of patents as belonging to design and manufacturing, cell culture systems, drug delivery, wound healing and tissue engineering clusters, respectively. The BNC group classified 44.5% of patents as design and manufacturing and 30.6% as drug delivery, as well as 5.6% and 19.4% of patents as wound healing and tissue engineering, respectively. In conclusion, this work compiled and classified patents addressing exclusively the use of nanocellulose in pharmaceuticals, providing information on its current status and trending advancements, considering environmental responsibility and sustainability in materials and products development for a greener upcoming future. Full article
(This article belongs to the Special Issue Advances in Polymeric Drug Delivery Systems)
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29 pages, 4204 KiB  
Review
Hydrogel-Based Therapeutics for Pancreatic Ductal Adenocarcinoma Treatment
by Jinlu Liu, Wenbi Wu, Qing Zhu and Hong Zhu
Pharmaceutics 2023, 15(10), 2421; https://doi.org/10.3390/pharmaceutics15102421 - 4 Oct 2023
Cited by 2 | Viewed by 1596
Abstract
Pancreatic ductal adenocarcinoma (PDAC), one of the deadliest malignancies worldwide, is characteristic of the tumor microenvironments (TME) comprising numerous fibroblasts and immunosuppressive cells. Conventional therapies for PDAC are often restricted by limited drug delivery efficiency, immunosuppressive TME, and adverse effects. Thus, effective and [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC), one of the deadliest malignancies worldwide, is characteristic of the tumor microenvironments (TME) comprising numerous fibroblasts and immunosuppressive cells. Conventional therapies for PDAC are often restricted by limited drug delivery efficiency, immunosuppressive TME, and adverse effects. Thus, effective and safe therapeutics are urgently required for PDAC treatment. In recent years, hydrogels, with their excellent biocompatibility, high drug load capacity, and sustainable release profiles, have been developed as effective drug-delivery systems, offering potential therapeutic options for PDAC. This review summarizes the distinctive features of the immunosuppressive TME of PDAC and discusses the application of hydrogel-based therapies in PDAC, with a focus on how these hydrogels remodel the TME and deliver different types of cargoes in a controlled manner. Furthermore, we also discuss potential drug candidates and the challenges and prospects for hydrogel-based therapeutics for PDAC. By providing a comprehensive overview of hydrogel-based therapeutics for PDAC treatment, this review seeks to serve as a reference for researchers and clinicians involved in developing therapeutic strategies targeting the PDAC microenvironment. Full article
(This article belongs to the Special Issue Advances in Polymeric Drug Delivery Systems)
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34 pages, 4354 KiB  
Review
Current Trends in Gelatin-Based Drug Delivery Systems
by Francesca Milano, Annalia Masi, Marta Madaghiele, Alessandro Sannino, Luca Salvatore and Nunzia Gallo
Pharmaceutics 2023, 15(5), 1499; https://doi.org/10.3390/pharmaceutics15051499 - 15 May 2023
Cited by 27 | Viewed by 4203
Abstract
Gelatin is a highly versatile natural polymer, which is widely used in healthcare-related sectors due to its advantageous properties, such as biocompatibility, biodegradability, low-cost, and the availability of exposed chemical groups. In the biomedical field, gelatin is used also as a biomaterial for [...] Read more.
Gelatin is a highly versatile natural polymer, which is widely used in healthcare-related sectors due to its advantageous properties, such as biocompatibility, biodegradability, low-cost, and the availability of exposed chemical groups. In the biomedical field, gelatin is used also as a biomaterial for the development of drug delivery systems (DDSs) due to its applicability to several synthesis techniques. In this review, after a brief overview of its chemical and physical properties, the focus is placed on the commonly used techniques for the development of gelatin-based micro- or nano-sized DDSs. We highlight the potential of gelatin as a carrier of many types of bioactive compounds and its ability to tune and control select drugs’ release kinetics. The desolvation, nanoprecipitation, coacervation, emulsion, electrospray, and spray drying techniques are described from a methodological and mechanistic point of view, with a careful analysis of the effects of the main variable parameters on the DDSs’ properties. Lastly, the outcomes of preclinical and clinical studies involving gelatin-based DDSs are thoroughly discussed. Full article
(This article belongs to the Special Issue Advances in Polymeric Drug Delivery Systems)
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29 pages, 2538 KiB  
Review
Smart Polymeric Nanoparticles in Cancer Immunotherapy
by Zhecheng Yu, Xingyue Shen, Han Yu, Haohong Tu, Chuda Chittasupho and Yunqi Zhao
Pharmaceutics 2023, 15(3), 775; https://doi.org/10.3390/pharmaceutics15030775 - 26 Feb 2023
Cited by 15 | Viewed by 3298
Abstract
Cancer develops with unexpected mutations and causes death in many patients. Among the different cancer treatment strategies, immunotherapy is promising with the benefits of high specificity and accuracy, as well as modulating immune responses. Nanomaterials can be used to formulate drug delivery carriers [...] Read more.
Cancer develops with unexpected mutations and causes death in many patients. Among the different cancer treatment strategies, immunotherapy is promising with the benefits of high specificity and accuracy, as well as modulating immune responses. Nanomaterials can be used to formulate drug delivery carriers for targeted cancer therapy. Polymeric nanoparticles used in the clinic are biocompatible and have excellent stability. They have the potential to improve therapeutic effects while significantly reducing off-target toxicity. This review classifies smart drug delivery systems based on their components. Synthetic smart polymers used in the pharmaceutical industry, including enzyme-responsive, pH-responsive, and redox-responsive polymers, are discussed. Natural polymers derived from plants, animals, microbes, and marine organisms can also be used to construct stimuli-responsive delivery systems with excellent biocompatibility, low toxicity, and biodegradability. The applications of smart or stimuli-responsive polymers in cancer immunotherapies are discussed in this systemic review. We summarize different delivery strategies and mechanisms that can be used in cancer immunotherapy and give examples of each case. Full article
(This article belongs to the Special Issue Advances in Polymeric Drug Delivery Systems)
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26 pages, 1604 KiB  
Review
Advancements in Rectal Drug Delivery Systems: Clinical Trials, and Patents Perspective
by Ritu Rathi, Sanshita, Alpesh Kumar, Vivekanand Vishvakarma, Kampanart Huanbutta, Inderbir Singh and Tanikan Sangnim
Pharmaceutics 2022, 14(10), 2210; https://doi.org/10.3390/pharmaceutics14102210 - 17 Oct 2022
Cited by 22 | Viewed by 9648
Abstract
The rectal route is an effective route for the local and systemic delivery of active pharmaceutical ingredients. The environment of the rectum is relatively constant with low enzymatic activity and is favorable for drugs having poor oral absorption, extensive first-pass metabolism, gastric irritation, [...] Read more.
The rectal route is an effective route for the local and systemic delivery of active pharmaceutical ingredients. The environment of the rectum is relatively constant with low enzymatic activity and is favorable for drugs having poor oral absorption, extensive first-pass metabolism, gastric irritation, stability issues in the gastric environment, localized activity, and for drugs that cannot be administered by other routes. The present review addresses the rectal physiology, rectal diseases, and pharmaceutical factors influencing rectal delivery of drugs and discusses different rectal drug delivery systems including suppositories, suspensions, microspheres, nanoparticles, liposomes, tablets, and hydrogels. Clinical trials on various rectal drug delivery systems are presented in tabular form. Applications of different novel drug delivery carriers viz. nanoparticles, liposomes, solid lipid nanoparticles, microspheres, transferosomes, nano-niosomes, and nanomicelles have been discussed and demonstrated for their potential use in rectal administration. Various opportunities and challenges for rectal delivery including recent advancements and patented formulations for rectal drug delivery have also been included. Full article
(This article belongs to the Special Issue Advances in Polymeric Drug Delivery Systems)
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