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Recent Advances in Polymeric Delivery Vehicles for Controlled and Sustained Drug Release

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

Deadline for manuscript submissions: 20 August 2024 | Viewed by 15321

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Special Issue Editors

Dr. Ping Hu

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Guest Editor

College of Pharmacy, Jinan University, Guangzhou 511436, China
Interests: sustained drug release; hydrogels; stimuli-responsive drug delivery; pharmacokinetics

Prof. Dr. Zheng Cai

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Co-Guest Editor

School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
Interests: controlled and sustained drug release; oral drug delivery systems; biopharmaceutics; pharmacokinetics; drug transporters

Special Issue Information

Dear Colleagues,

The latest advances in drug delivery systems are aimed at delivery drugs in controlled fashions from both temporal and spartial perspectives. Polymers have recently been employed in these approaches for drug delivery, tissue engineering, cell encapsulation, the fabrication of medical devices, and a diversity of other biomedical applications. These recent successful applications have demonstrated the superior potential of such polymeric drug delivery systems in biomedicine.

This Special Issue aims to provide an updated account of recent advances in the synthesis, characterization, engineering, and use of polymers, being synthetic or natural, for drug delivery and sustained drug release. We invite authors to report their recently developed novel polymer-based carriers in therapeutics and diagnoses that overcome the limitations associated with drug administration and enhance the life quality of patients.

Research areas of particular interest include (but are not limited to) the following:

Long-acting parenteral formulations;
Preparation and evaluation of microparticles;
Hydrogel-based formulations;
Controlled-release systems for topical agents or cosmetics;
Nanomaterials in drug delivery.

We look forward to receiving your contributions.

Dr. Ping Hu
Prof. Dr. Zheng Cai
Guest Editors

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. 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
sustained drug release
polymers
stimuli-responsive drug delivery
hydrogels
microspheres
nanoparticles
topical drug delivery
biomaterials

Published Papers (9 papers)

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Research

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18 pages, 4718 KiB

Open AccessArticle

The Development of a Stable Peptide-Loaded Long-Acting Injection Formulation through a Comprehensive Understanding of Peptide Degradation Mechanisms: A QbD-Based Approach

by Yingxin Xiong, Jiawei Wang, Xing Zhou and Xiaohui Li

Pharmaceutics 2024, 16(2), 266; https://doi.org/10.3390/pharmaceutics16020266 - 13 Feb 2024

Viewed by 711

Abstract

Quality by design (QbD) serves as a systematic approach to pharmaceutical development, beginning with predefined objectives and emphasizing an understanding of the product based on sound science and risk management. The purpose of this study is to utilize the QbD concept to develop a stable peptide-loaded long-acting injection formulation. An in-depth comprehension of peptide degradation mechanisms was achieved through forced degradation investigations, elucidating (acid) hydrolysis and oxidation as the primary degradation pathways for the peptide ACTY116. The quality built into the product was focused on risk assessment, for which the critical material attributes (CMAs) and critical process parameters (CPPs) associated with the critical quality attributes (CQAs) of each formulation were identified, leading to the development of the corresponding control strategies. CQAs for three LAI (long-acting injectable) formulations were enhanced by taking the right control strategies. The LAI formulation exhibiting the highest stability for ACTY116 was chosen for subsequent pharmacokinetic investigations in rats. The objective of addressing peptide chemical instability and in vivo long-acting release was achieved. For other molecules with susceptible functionalities like amide bonds, amino groups, and hydroxyl groups, the utilization of PLGA-based in situ gel as an LAI formulation for stabilizing molecules provides valuable insights. Full article

(This article belongs to the Special Issue Recent Advances in Polymeric Delivery Vehicles for Controlled and Sustained Drug Release)

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22 pages, 4494 KiB

Open AccessArticle

Nano-Topographically Guided, Biomineralized, 3D-Printed Polycaprolactone Scaffolds with Urine-Derived Stem Cells for Promoting Bone Regeneration

by Fei Xing, Hui-Yuan Shen, Man Zhe, Kai Jiang, Jun Lei, Zhou Xiang, Ming Liu, Jia-Zhuang Xu and Zhong-Ming Li

Pharmaceutics 2024, 16(2), 204; https://doi.org/10.3390/pharmaceutics16020204 - 31 Jan 2024

Viewed by 751

Abstract

Currently, biomineralization is widely used as a surface modification approach to obtain ideal material surfaces with complex hierarchical nanostructures, morphologies, unique biological functions, and categorized organizations. The fabrication of biomineralized coating for the surfaces of scaffolds, especially synthetic polymer scaffolds, can alter surface characteristics, provide a favorable microenvironment, release various bioactive substances, regulate the cellular behaviors of osteoblasts, and promote bone regeneration after implantation. However, the biomineralized coating fabricated by immersion in a simulated body fluid has the disadvantages of non-uniformity, instability, and limited capacity to act as an effective reservoir of bioactive ions for bone regeneration. In this study, in order to promote the osteoinductivity of 3D-printed PCL scaffolds, we optimized the surface biomineralization procedure by nano-topographical guidance. Compared with biomineralized coating constructed by the conventional method, the nano-topographically guided biomineralized coating possessed more mineral substances and firmly existed on the surface of scaffolds. Additionally, nano-topographically guided biomineralized coating possessed better protein adsorption and ion release capacities. To this end, the present work also demonstrated that nano-topographically guided biomineralized coating on the surface of 3D-printed PCL scaffolds can regulate the cellular behaviors of USCs, guide the osteogenic differentiation of USCs, and provide a biomimetic microenvironment for bone regeneration. Full article

(This article belongs to the Special Issue Recent Advances in Polymeric Delivery Vehicles for Controlled and Sustained Drug Release)

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14 pages, 4919 KiB

Open AccessArticle

Thermo-Responsive Hydrogels Encapsulating Targeted Core–Shell Nanoparticles as Injectable Drug Delivery Systems

by Elif Gulin Ertugral-Samgar, Ali Murad Ozmen and Ozgul Gok

Pharmaceutics 2023, 15(9), 2358; https://doi.org/10.3390/pharmaceutics15092358 - 21 Sep 2023

Cited by 2 | Viewed by 1349

Abstract

As therapeutic agents that allow for minimally invasive administration, injectable biomaterials stand out as effective tools with tunable properties. Furthermore, hydrogels with responsive features present potential platforms for delivering therapeutics to desired sites in the body. Herein, temperature-responsive hydrogel scaffolds with embedded targeted nanoparticles were utilized to achieve controlled drug delivery via local drug administration. Poly(N-isopropylacrylamide) (pNIPAM) hydrogels, prepared with an ethylene-glycol-based cross-linker, demonstrated thermo-sensitive gelation ability upon injection into environments at body temperature. This hydrogel network was engineered to provide a slow and controlled drug release profile by being incorporated with curcumin-loaded nanoparticles bearing high encapsulation efficiency. A core (alginate)–shell (chitosan) nanoparticle design was preferred to ensure the stability of the drug molecules encapsulated in the core and to provide slower drug release. Nanoparticle-embedded hydrogels were shown to release curcumin at least four times slower compared to the free nanoparticle itself and to possess high water uptake capacity and more mechanically stable viscoelastic behavior. Moreover, this therapy has the potential to specifically address tumor tissues over-expressing folate receptors like ovaries, as the nanoparticles target the receptors by folic acid conjugation to the periphery. Together with its temperature-driven injectability, it can be concluded that this hydrogel scaffold with drug-loaded and embedded folate-targeting nanoparticles would provide effective therapy for tumor tissues accessible via minimally invasive routes and be beneficial for post-operative drug administration after tumor resection. Full article

(This article belongs to the Special Issue Recent Advances in Polymeric Delivery Vehicles for Controlled and Sustained Drug Release)

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13 pages, 3615 KiB

Open AccessArticle

Design of Dual-Targeted pH-Sensitive Hybrid Polymer Micelles for Breast Cancer Treatment: Three Birds with One Stone

by Degong Yang, Ziqing Li, Yinghui Zhang, Xuejun Chen, Mingyuan Liu and Chunrong Yang

Pharmaceutics 2023, 15(6), 1580; https://doi.org/10.3390/pharmaceutics15061580 - 24 May 2023

Cited by 1 | Viewed by 1325

Abstract

Breast cancer has a high prevalence in the world and creates a substantial socio-economic impact. Polymer micelles used as nano-sized polymer therapeutics have shown great advantages in treating breast cancer. Here, we aim to develop a dual-targeted pH-sensitive hybrid polymer (HPPF) micelles for improving the stability, controlled-release ability and targeting ability of the breast cancer treatment options. The HPPF micelles were constructed using the hyaluronic acid modified polyhistidine (HA-PHis) and folic acid modified Plannick (PF127-FA), which were characterized via ¹H NMR. The optimized mixing ratio (HA-PHis:PF127-FA) was 8:2 according to the change of particle size and zeta potential. The stability of HPPF micelles were enhanced with the higher zeta potential and lower critical micelle concentration compared with HA-PHis and PF127-FA. The drug release percents significantly increased from 45% to 90% with the decrease in pH, which illustrated that HPPF micelles were pH-sensitive owing to the protonation of PHis. The cytotoxicity, in vitro cellular uptake and in vivo fluorescence imaging experiments showed that HPPF micelles had the highest targeting ability utilizing FA and HA, compared with HA-PHis and PF127-FA. Thus, this study constructs an innovative nano-scaled drug delivery system, which provides a new strategy for the treatment of breast cancer. Full article

(This article belongs to the Special Issue Recent Advances in Polymeric Delivery Vehicles for Controlled and Sustained Drug Release)

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15 pages, 3963 KiB

Open AccessArticle

Influence of PEGDA Molecular Weight and Concentration on the In Vitro Release of the Model Protein BSA–FITC from Photo Crosslinked Systems

by Natalia Rekowska, Katharina Wulf, Daniela Koper, Volkmar Senz, Hermann Seitz, Niels Grabow and Michael Teske

Pharmaceutics 2023, 15(4), 1039; https://doi.org/10.3390/pharmaceutics15041039 - 23 Mar 2023

Cited by 1 | Viewed by 1781

Abstract

Novel 3D printing techniques enable the development of medical devices with drug delivery systems that are tailored to the patient in terms of scaffold shape and the desired pharmaceutically active substance release. Gentle curing methods such as photopolymerization are also relevant for the incorporation of potent and sensitive drugs including proteins. However, retaining the pharmaceutical functions of proteins remains challenging due to the possible crosslinking between the functional groups of proteins, and the used photopolymers such as acrylates. In this work, the in vitro release of the model protein drug, albumin–fluorescein isothiocyanate conjugate (BSA–FITC) from differently composed, photopolymerized poly(ethylene) glycol diacrylate (PEGDA), an often employed, nontoxic, easily curable resin, was investigated. Different PEGDA concentrations in water (20, 30, and 40 wt %) and their different molecular masses (4000, 10,000, and 20,000 g/mol) were used to prepare a protein carrier with photopolymerization and molding. The viscosity measurements of photomonomer solutions revealed exponentially increasing values with increasing PEGDA concentration and molecular mass. Polymerized samples showed increasing medium uptake with an increasing molecular mass and decreasing uptake with increasing PEGDA content. Therefore, the modification of the inner network resulted in the most swollen samples (20 wt %) also releasing the highest amount of incorporated BSA–FITC for all PEGDA molecular masses. Full article

(This article belongs to the Special Issue Recent Advances in Polymeric Delivery Vehicles for Controlled and Sustained Drug Release)

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11 pages, 2006 KiB

Open AccessArticle

A Pilot Study Exploiting the Industrialization Potential of Solid Lipid Nanoparticle-Based Metered-Dose Inhalers

by Lei Shu, Wenhua Wang, Chon-iong Ng, Xuejuan Zhang, Ying Huang, Chuanbin Wu, Xin Pan and Zhengwei Huang

Pharmaceutics 2023, 15(3), 866; https://doi.org/10.3390/pharmaceutics15030866 - 07 Mar 2023

Viewed by 1673

Abstract

Background: Delivery of inhalable nanoparticles through metered-dose inhalers (MDI) is a promising approach to treat lung disease such as asthma and chronic obstructive pulmonary disease. Nanocoating of the inhalable nanoparticles helps in stability and cellular uptake enhancement but complicates the production process. Thus, it is meaningful to accelerate the translation process of MDI encapsulating inhalable nanoparticles with nanocoating structure. Methods: In this study, solid lipid nanoparticles (SLN) are selected as a model inhalable nanoparticle system. An established reverse microemulsion strategy was utilized to explore the industrialization potential of SLN-based MDI. Three categories of nanocoating with the functions of stabilization (by Poloxamer 188, encoded as SLN(0)), cellular uptake enhancement (by cetyltrimethylammonium bromide, encoded as SLN(+)), and targetability (by hyaluronic acid, encoded as SLN(−)) were constructed upon SLN, whose particle size distribution and zeta-potential were characterized. Subsequently, SLN were loaded into MDI, and evaluated for the processing reliability, physicochemical nature, formulation stability, and biocompatibility. Results: The results elucidated that three types of SLN-based MDI were successfully fabricated with good reproducibility and stability. Regarding safety, SLN(0) and SLN(−) showed negligible cytotoxicity on cellular level. Conclusions: This work serves as a pilot study for the scale-up of SLN-based MDI, and could be useful for the future development of inhalable nanoparticles. Full article

(This article belongs to the Special Issue Recent Advances in Polymeric Delivery Vehicles for Controlled and Sustained Drug Release)

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21 pages, 3836 KiB

Open AccessArticle

Coatings of Cyclodextrin/Citric-Acid Biopolymer as Drug Delivery Systems: A Review

by Karen Escobar, Karla A. Garrido-Miranda, Ruth Pulido, Nelson Naveas, Miguel Manso-Silván and Jacobo Hernandez-Montelongo

Pharmaceutics 2023, 15(1), 296; https://doi.org/10.3390/pharmaceutics15010296 - 16 Jan 2023

Cited by 6 | Viewed by 2832

Abstract

In the early 2000s, a method for cross-linking cyclodextrins (CDs) with citric acid (CTR) was developed. This method was nontoxic, environmentally friendly, and inexpensive compared to the others previously proposed in the literature. Since then, the CD/CTR biopolymers have been widely used as a coating on implants and other materials for biomedical applications. The present review aims to cover the chemical properties of CDs, the synthesis routes of CD/CTR, and their applications as drug-delivery systems when coated on different substrates. Likewise, the molecules released and other pharmaceutical aspects involved are addressed. Moreover, the different methods of pretreatment applied on the substrates before the in situ polymerization of CD/CTR are also reviewed as a key element in the final functionality. This process is not trivial because it depends on the surface chemistry, geometry, and physical properties of the material to be coated. The biocompatibility of the polymer was also highlighted. Finally, the mechanisms of release generated in the CD/CTR coatings were analyzed, including the mathematical model of Korsmeyer–Peppas, which has been dominantly used to explain the release kinetics of drug-delivery systems based on these biopolymers. The flexibility of CD/CTR to host a wide variety of drugs, of the in situ polymerization to integrate with diverse implantable materials, and the controllable release kinetics provide a set of advantages, thereby ensuring a wide range of future uses. Full article

(This article belongs to the Special Issue Recent Advances in Polymeric Delivery Vehicles for Controlled and Sustained Drug Release)

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19 pages, 2302 KiB

Open AccessArticle

Application of Box-Behnken Design in the Preparation, Optimization, and In-Vivo Pharmacokinetic Evaluation of Oral Tadalafil-Loaded Niosomal Film

by Kawthar K. Abla, Amina T. Mneimneh, Ahmed N. Allam and Mohammed M. Mehanna

Pharmaceutics 2023, 15(1), 173; https://doi.org/10.3390/pharmaceutics15010173 - 03 Jan 2023

Cited by 5 | Viewed by 1999

Abstract

Benign prostatic hyperplasia (BPH) affects about 90% of men whose ages are over 65. Tadalafil, a selective PDE-5 inhibitor, was approved by FDA for BPH, however, its poor aqueous solubility and bioavailability are considered major drawbacks. This work intended to develop and evaluate oral fast dissolving film containing tadalafil-loaded niosomes for those who cannot receive the oral dosage form. Niosomes were statistically optimized by Box-Behnken experimental design and loaded into a polymeric oral film. Niosomes were assessed for their vesicular size, uniformity, and zeta potential. The thickness, content uniformity, folding endurance, tensile strength, disintegration time, and surface morphology were evaluated for the prepared polymeric film. The optimized niosomes revealed high entrapment efficiency (99.78 ± 2.132%) and the film was smooth with good flexibility and convenient thickness (110 ± 10 µm). A fast release of tadalafil was achieved within 5 min significantly faster than the niosomes-free drug film. The in-vivo bioavailability in rats established that the optimized niosomal film enhanced tadalafil systemic absorption, with higher peak concentration (C_max = 0.63 ± 0.03 µg/mL), shorter T_max value (0.66-fold), and relative bioavailability of 118.4% compared to the marketed tablet. These results propose that the oral film of tadalafil-loaded niosomes is a suitable therapeutic application that can be passed with ease to geriatric patients who suffer from BPH. Full article

(This article belongs to the Special Issue Recent Advances in Polymeric Delivery Vehicles for Controlled and Sustained Drug Release)

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Review

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24 pages, 4457 KiB

Open AccessReview

Engineered Extracellular Vesicles for Drug Delivery in Therapy of Stroke

by Waqas Ahmed, Muhammed Shibil Kuniyan, Aqil Mohammad Jawed and Lukui Chen

Pharmaceutics 2023, 15(9), 2173; https://doi.org/10.3390/pharmaceutics15092173 - 22 Aug 2023

Cited by 5 | Viewed by 1684

Abstract

Extracellular vesicles (EVs) are promising therapeutic modalities for treating neurological conditions. EVs facilitate intercellular communication among brain cells under normal and abnormal physiological conditions. The potential capability of EVs to pass through the blood–brain barrier (BBB) makes them highly promising as nanocarrier contenders for managing stroke. EVs possess several potential advantages compared to existing drug-delivery vehicles. These advantages include their capacity to surpass natural barriers, target specific cells, and stability within the circulatory system. This review explores the trafficking and cellular uptake of EVs and evaluates recent findings in the field of EVs research. Additionally, an overview is provided of the techniques researchers utilize to bioengineer EVs for stroke therapy, new results on EV–BBB interactions, and the limitations and prospects of clinically using EVs for brain therapies. The primary objective of this study is to provide a comprehensive analysis of the advantages and challenges related to engineered EVs drug delivery, specifically focusing on their application in the treatment of stroke. Full article

(This article belongs to the Special Issue Recent Advances in Polymeric Delivery Vehicles for Controlled and Sustained Drug Release)

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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: Ultrasound-responsive nanoparticles for nitric oxide release to inhibit breast cancer
Author: Yang
Highlights: 1. we successfully constructed the ultrasound-responsive nanodrug delivery platform (PLGA nanoparticles load with LA and Fe3O4 NPs) 2. LA could be released rapidly under the ultrasound irradiation 3. LA as NO donor could rapidly react with H2O2 in the tumor microenvironment to generate NO for gas therapy 4. Fe3O4 NPs could generate the contrast enhancement in photoacoustic imaging

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