PLGA Micro/Nanoparticles in Drug Delivery

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

Deadline for manuscript submissions: 30 September 2026 | Viewed by 9166

Special Issue Editors


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Guest Editor
Department of Pharmacy—Pharmaceutical Sciences, University of Bari, 70125 Bari, Italy
Interests: nanomedicine; drug delivery; controlled drug delivery; microfluidics
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Department of Drug Science and Technology, University of Turin, 10125 Turin, Italy
Interests: drug delivery systems; biocompatible nanocarriers; active targeting; liposomes; polymer nanoparticles

Special Issue Information

Dear Colleagues,

Polymer-based drug delivery systems have gained increasing attention as a promising platform for a variety of therapies, thanks to their favourable properties such as biocompatibility, tunable physicochemical properties, protection from in vivo degradation, controlled release of therapeutic agents, and ease of surface modification for targeted delivery. Poly(lactic-co-glycolic acid) (PLGA) micro- and nanoparticles have emerged as versatile carriers in drug delivery systems due to their biodegradability and ability to encapsulate a wide range of therapeutic agents.

This Special Issue focuses on the latest advancements and original work on PLGA-based drug delivery systems and their biomedical applications. Topics include surface functionalization methods, preparation techniques, challenges related to scale-up and interactions with biological systems, as well as translation and comparative studies. Research areas of interest may include (but are not limited to) the following:

  • Delivery and controlled release systems for drugs, vaccines, and biopharmaceuticals;
  • Drug targeting;
  • Innovative techniques for the production of PLGA micro- and nanoparticles;
  • Functionalization or medication of PLGA;
  • Improvement of nanocarrier stability.

Given the importance of research in this field, we are pleased to invite you to submit your original research articles and reviews to this Special Issue and contribute to a more sustainable and inclusive world.

We look forward to receiving your contributions.

Dr. Ilaria Arduino
Dr. Ilaria Andreana
Guest Editors

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Keywords

  • micro- and nanotechnology
  • particle manufacturing
  • targeted delivery
  • particle characterization
  • biocompatibility
  • solubility enhancement

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Published Papers (5 papers)

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Research

28 pages, 6693 KB  
Article
Optimization of Microfluidizer-Produced PLGA Nano-Micelles for Enhanced Stability and Antioxidant Efficacy: A Quality by Design Approach
by Esma Nur Develi Arslanhan, Fatemeh Bahadori, Zahra Eskandari, Muhammed Zahid Kasapoglu and Erkan Mankan
Pharmaceutics 2026, 18(1), 25; https://doi.org/10.3390/pharmaceutics18010025 - 25 Dec 2025
Viewed by 855
Abstract
Introduction: In this study, we aimed to optimize the microfluidizer-based preparation of poly(lactic-co-glycolic acid) nano-micelles (PLGANM), increasingly used for parenteral delivery of poorly water-soluble drugs but typically exhibiting poor physical stability when produced by conventional methods. Method: By systematically tuning microfluidization (MFZ) parameters, [...] Read more.
Introduction: In this study, we aimed to optimize the microfluidizer-based preparation of poly(lactic-co-glycolic acid) nano-micelles (PLGANM), increasingly used for parenteral delivery of poorly water-soluble drugs but typically exhibiting poor physical stability when produced by conventional methods. Method: By systematically tuning microfluidization (MFZ) parameters, we demonstrate an efficient strategy to enhance PLGANM stability and ensure robust, scalable manufacturing, relevant for long-term storage and clinical translation applications. The influence of several key factors designed by Central Composite Design (CCD), including the amount of PLGA and Tween 80, homogenization pressure, and number of passes of MFZ on the size, polydispersity (measured by DLS), and hence stability of the PLGANM, was analyzed for 60 days. 60 PLGANMs produced by the MFZ method (PMFZ) were compared with the PLGANM consisting of equivalent amounts of PLGA and T80 produced using the traditional oil-in-water method (POW). Desired limits were set to minimize standard deviations for Z-average, Zeta Potential, and PDI. Results: Coded variables for optimized PMFZ (OPMFZ) were found to be 82.96 mg PLGA, 6.78 mL 5% T80, 11,000 psi pressure, and 1 pass. Conclusions: This study demonstrates that microfluidization, when guided by a QbD framework, offers precise control over particle attributes and enables reproducible production of stable PLGANM. Full article
(This article belongs to the Special Issue PLGA Micro/Nanoparticles in Drug Delivery)
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18 pages, 2670 KB  
Article
Effects of Polysaccharide Coating on Cell-Surface Association and Endocytic Uptake of PLGA Nanomicelles in MCF-7 Cells
by Abdulkadir Bahadir Alkan, Esma Nur Develi Arslanhan, Fatemeh Bahadori, Muhammed Zahid Kasapoglu, Fahri Akbas, Seda Susgun, Zahra Eskandari and Ebru Toksoy Oner
Pharmaceutics 2026, 18(1), 17; https://doi.org/10.3390/pharmaceutics18010017 - 22 Dec 2025
Cited by 2 | Viewed by 928
Abstract
Background: Targeting cancer tumors using PLGA (Poly(D, L-lactide-co-glycolide)) nanoparticles (NPs) requires clathrin-mediated endocytosis (CME) and lysosomal degradation to provide release within cancer cells. However, Caveolae-mediated endocytosis (CavME) provides lysosomal escape, which is favorable in oral applications. Macropinocytosis (MPC) is a non-targeted way of [...] Read more.
Background: Targeting cancer tumors using PLGA (Poly(D, L-lactide-co-glycolide)) nanoparticles (NPs) requires clathrin-mediated endocytosis (CME) and lysosomal degradation to provide release within cancer cells. However, Caveolae-mediated endocytosis (CavME) provides lysosomal escape, which is favorable in oral applications. Macropinocytosis (MPC) is a non-targeted way of endocytosis, used by immune cells. Methods: In this proof-of-concept study, we investigated how polysaccharide surface coatings modulate the endocytic uptake of FITC-labeled PLGA nanomicelles (FPM) in MCF-7 breast cancer cells using spectrophotometry. This research involved the surface modification of FPM using polysaccharides: cellulose (FPCM) as a polyglucan and Halomonas Levan (FPLM) as a polyfructan, to modify the NP and cell-surface association. Results: MPC was found to be the major internalization pathway for the nanomicelles ~200 nm. However, after surface modification, FPCM and FPM remained highly MPC-dependent with additional CavME/CME involvement, whereas FPLM showed relatively reduced MPC dependence and a higher CME contribution. Conclusion: Overall, the results indicate that simple polysaccharide coatings can bias the relative use of MPC, CME, and CavME for PLGA nanomicelles in MCF-7 cells, providing a basis for pathway-oriented nanocarrier design. Validation by flow cytometry, studies in additional breast cancer cell lines, and transporter-level investigations will be needed to generalize and refine these findings. Full article
(This article belongs to the Special Issue PLGA Micro/Nanoparticles in Drug Delivery)
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24 pages, 5480 KB  
Article
Liposomal Co-Delivery of Acteoside, CBD, and Naringenin: A Synergistic Strategy Against Gliomas
by Jagoda Szkudlarek, Ludwika Piwowarczyk, Violetta Krajka-Kuźniak, Aleksandra Majchrzak-Celińska, Szymon Tomczak, Mikołaj Baranowski, Rafał Pietrzyk, Aneta Woźniak-Braszak and Anna Jelińska
Pharmaceutics 2025, 17(8), 1026; https://doi.org/10.3390/pharmaceutics17081026 - 7 Aug 2025
Cited by 2 | Viewed by 1596
Abstract
Background/Objectives: Adult-type diffuse gliomas, including astrocytoma and glioblastoma multiforme (GBM), are brain tumors with a very poor prognosis. While current treatment options for glioma patients are not providing satisfactory outcomes, research indicates that natural compounds could serve as alternative treatments. However, their [...] Read more.
Background/Objectives: Adult-type diffuse gliomas, including astrocytoma and glioblastoma multiforme (GBM), are brain tumors with a very poor prognosis. While current treatment options for glioma patients are not providing satisfactory outcomes, research indicates that natural compounds could serve as alternative treatments. However, their low bioavailability requires nanotechnology solutions, such as liposomes. Methods: In this study, we propose the co-encapsulation of acteoside (ACT) with other natural compounds, cannabidiol (CBD) or naringenin (NG), in a cationic liposomal nanoformulation consisting of DOTAP and POPC lipids, which were prepared using the dry lipid film method. The liposomes were characterized by their physicochemical properties, including particle size, zeta potential, and polydispersity index (PDI), with additional analyses performed using 1H Nuclear Magnetic Resonance (NMR). Furthermore, biological experiments were performed with U-87 MG astrocytoma and U-138 MG GBM cell lines and non-cancerous MRC-5 lung fibroblasts using the MTT assay and evaluating the expression of Bax and Bcl-xL to evaluate their potential as anticancer agents. Conclusions: The IC50 values for the nanoformulations in U-138 MG cells at 48 h were 6 µM for ACT + CBD and 5 µM for ACT + NG. ACT and CBD or NG demonstrated a potential synergistic effect against GBM in a liposomal formulation. Notably, treatment with ACT + CBD (5 µM) and ACT + NG (5 µM) liposomal formulations significantly upregulated Bax protein level in U-138 cells at both 24 and 48 h. In parallel, ACT + CBD (5 µM) also modulated Bcl-xL protein level in both U-138 MG and U-87 MG cell lines at the same time points. The obtained nanoformulations were homogeneous and stable for 21 days, evidenced by a narrow particle size distribution, a low polydispersity index (PDI) < 0.3, and a positive zeta potential. Full article
(This article belongs to the Special Issue PLGA Micro/Nanoparticles in Drug Delivery)
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17 pages, 8085 KB  
Article
Synthesis and Characterization of Poly(Lactic-Co-Glycolic Acid)–Paclitaxel (PLGA-PTX) Nanoparticles Evaluated in Ovarian Cancer Models
by Sylwia A. Dragulska, Maxier Acosta Santiago, Sabina Swierczek, Linus Chuang, Olga Camacho-Vanegas, Sandra Catalina Camacho, Maria M. Padron-Rhenals, John A. Martignetti and Aneta J. Mieszawska
Pharmaceutics 2025, 17(6), 689; https://doi.org/10.3390/pharmaceutics17060689 - 23 May 2025
Cited by 3 | Viewed by 2098
Abstract
We developed a novel biodegradable poly(lactic-co-glycolic acid) (PLGA) polymer chemically modified with paclitaxel (PTX) to form a PLGA-PTX hybrid. Pre-modification of PTX enhanced its loading in PLGA-PTX nanoparticles (NPs). Background/Objectives: PTX is one of the most effective chemotherapy agents used in cancer [...] Read more.
We developed a novel biodegradable poly(lactic-co-glycolic acid) (PLGA) polymer chemically modified with paclitaxel (PTX) to form a PLGA-PTX hybrid. Pre-modification of PTX enhanced its loading in PLGA-PTX nanoparticles (NPs). Background/Objectives: PTX is one of the most effective chemotherapy agents used in cancer therapy. The primary mode of PTX’s action is the hyperstabilization of microtubules leading to cell growth arrest. Although highly potent, the drug is water insoluble and requires the Cremophor EL excipient. The toxic effects of the free drug (e.g., neurotoxicity) as well as its solubilizing agent are well established. Thus, there is strong clinical rationale and need for exploring alternative PTX delivery approaches, retaining biological activity and minimizing systemic effects. Methods: The PTX modification method features reacting the C-2′ and C-7 residues with a linker (succinic anhydride) to produce easily accessible carboxyl groups on the PTX for enhanced coupling to the hydroxyl group of PLGA. The PLGA-PTX hybrid, formed via esterification reaction, was used to formulate lipid-coated PLGA-PTX NPs. As proof of concept, the PLGA-PTX NPs were tested in ovarian cancer (OvCA) models, including several patient-derived cell lines (PDCLs), one of which was generated from a platinum-resistant patient. Results: The PLGA-PTX NPs critically remained stable in water and serum while enabling slow drug release. Importantly, PLGA-PTX NPs demonstrated biological activity. Conclusions: We suggest that this approach offers both a new and effective PTX formulation and a possible path towards the development of a new generation of OvCA treatment. Full article
(This article belongs to the Special Issue PLGA Micro/Nanoparticles in Drug Delivery)
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19 pages, 2608 KB  
Article
Delivery of PLGA-Loaded Influenza Vaccine Microparticles Using Dissolving Microneedles Induces a Robust Immune Response
by Emmanuel Adediran, Tanisha Arte, Dedeepya Pasupuleti, Sharon Vijayanand, Revanth Singh, Parth Patel, Mahek Gulani, Amarae Ferguson, Mohammad Uddin, Susu M. Zughaier and Martin J. D’Souza
Pharmaceutics 2025, 17(4), 510; https://doi.org/10.3390/pharmaceutics17040510 - 12 Apr 2025
Cited by 9 | Viewed by 2784
Abstract
Background: Influenza virus is one of the major respiratory virus infections that is a global health concern. Although there are already approved vaccines, most are administered via the intramuscular route, which is usually painful, leading to vaccine hesitancy. To this end, exploring the [...] Read more.
Background: Influenza virus is one of the major respiratory virus infections that is a global health concern. Although there are already approved vaccines, most are administered via the intramuscular route, which is usually painful, leading to vaccine hesitancy. To this end, exploring the non-invasive, transdermal vaccination route using dissolving microneedles would significantly improve vaccine compliance. Research on innovative vaccine delivery systems, such as antigen-loaded PLGA microparticles, has the potential to pave the way for a broader range of vaccine candidates. Methods: In this proof-of-concept study, a combination of the inactivated influenza A H1N1 virus and inactivated influenza A H3N2 virus were encapsulated in a biodegradable poly (lactic-co-glycolic acid) (PLGA) polymeric matrix within microparticles, which enhanced antigen presentation. The antigen PLGA microparticles were prepared separately using a double emulsion (w/o/w), lyophilized, and characterized. Next, the vaccine microparticles were assessed in vitro in dendritic cells (DC 2.4) for immunogenicity. To explore pain-free transdermal vaccination, the vaccine microparticles were loaded into dissolving microneedles and administered in mice (n = 5). Results: Our vaccination study demonstrated that the microneedle-based vaccine elicited strong humoral responses as demonstrated by high antigen-specific IgA, IgG, IgG1, and IgG2a antibodies in serum samples and IgA in lung supernatant. Further, the vaccine also elicited a strong cellular response as evidenced by high levels of CD4+ and CD8a+ T cells in lymphoid organs such as the lymph nodes and spleen. Conclusion: The delivery of influenza vaccine-loaded PLGA microparticles using microneedles would be beneficial to individuals experiencing needle-phobia, as well as the geriatric and pediatric population. Full article
(This article belongs to the Special Issue PLGA Micro/Nanoparticles in Drug Delivery)
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