Current trends and prospects in the development of pharmaceutical compositions with prolonged action based on poly(lactide-co-glicolide): a literature review
DOI:
https://doi.org/10.5281/zenodo.18888711Keywords:
pharmaceutical compositions,, poly(lactide-co-glycolide),, polymer,, microspheres,, in situ implants,, prolonged release,, active pharmaceutical ingredientAbstract
The development of prolonged-action drugs is a relevant and promising area of modern pharmaceutical science and practice. One of the best polymer carriers for creating prolonged-release dosage forms is considered to be poly(lactide-co-glycolide) (PLGA), due to its biocompatibility, biodegradability, and controllable physicochemical properties. The aim of the work is to systematically analyze the scientific literature on the use of poly (polylactide-co-glycolide) in the development of prolonged-action pharmaceutical compositions, including the characterization of the physicochemical properties of the polymer, research on the range of drugs based on it, a review of methods for their production, and the identification of promising areas for further scientific research. The research methodology was based on a comprehensive analytical review of scientific papers published in journals indexed in the international scientometric databases Scopus and Web of Science, as well as those presented in the specialized PubMed database. The work uses methods of critical analysis, information structuring, comparative data evaluation, and generalization of results. This work presents an analytical literature review on the use of PLGA polymer carriers for the development of pharmaceutical compositions with controlled and prolonged release of active pharmaceutical ingredients (APIs). The methods of synthesis and physicochemical properties of PLGA are characterized, and the key factors affecting polymer degradation are identified. A comprehensive analysis of the pharmaceutical market for PLGA-based drugs is performed. Various types of PLGA-based injectable pharmaceutical compositions are characterized, namely systems based on polymer microspheres and gels that form an in situ implant after subcutaneous administration, including an analysis of the mechanisms of API release from these forms. Modern promising methods for obtaining PLGA microspheres with prolonged API release are described, in particular emulsification, coacervation, spray drying, supercritical fluids, and microfluidic technologies. The properties of gels that form in situ implants are characterized, including phase inversion mechanisms and factors affecting the kinetics of API release. The main difficulties in the development of PLGA-based pharmaceutical compositions are identified, in particular, the problem of initial rapid API release, the lack of standardized methods for assessing the kinetics of active substance release, and the influence of polymer property variability on the reproducibility of the characteristics of finished dosage forms. The results of the study emphasize the effectiveness of using PLGA as a polymer carrier for the creation of highly effective prolonged-action drugs used to treat a wide range of diseases. The key tasks for future scientific research are to develop and validate standardized methods for studying the kinetics of active substance release, and to evaluate the effectiveness of PLGA systems using correlations between in vitro and in vivo studies. In addition, the creation of unified approaches to quality control of production processes remains a relevant area of focus in order to ensure the reproducibility and stability of innovative pharmaceutical compositions based on PLGA.
References
Yang J, Zeng H, Luo Y, Chen Y, Wang M, Wu C, Hu P. Recent Applications of PLGA in Drug Delivery Systems. Polymers. 2024;16(18):2606. https://doi.org/10.3390/polym16182606
Rocha CV, Gonçalves V, da Silva MC, Bañobre-López M, Gallo J. PLGA-Based Composites for Various Biomedical Applications. Int J Mol Sci. 2022;23(4):2034. https://doi.org/10.3390/ijms23042034
Little A, Wemyss AM, Haddleton DM, Tan B, Sun Z, Ji Y, Wan C. Synthesis of Poly(Lactic Acid-co-Glycolic Acid) Copolymers with High Glycolide Ratio by Ring-Opening Polymerisation. Polymers. 2021;13(15):2458. https://doi.org/10.3390/polym13152458
Lu Y, Cheng D, Niu B, Wang X, Wu X, Wang A. Properties of Poly (Lactic-co-Glycolic Acid) and Progress of Poly (Lactic-co-Glycolic Acid)-Based Biodegradable Materials in Biomedical Research. Pharmaceuticals. 2023;16(3):454. https://doi.org/10.3390/ph16030454
Choi SY, Park SJ, Kim WJ, Yang JE, Lee H, Shin J, Lee SY. One-step fermentative production of poly(lactate-co-glycolate) from carbohydrates in Escherichia coli. Nat Biotechnol. 2016;34(4):435–440. https://doi.org/10.1038/nbt.3485
Mahar R, Chakraborty A, Nainwal N, Bahuguna R, Sajwan M, Jakhmola V. Application of PLGA as a Biodegradable and Biocompatible Polymer for Pulmonary Delivery of Drugs. AAPS PharmSciTech. 2023;24(1):39. https://doi.org/10.1208/s12249-023-02502-1
Chavan YR, Tambe SM, Jain DD, Khairnar SV, Amin PD. Redefining the importance of polylactide-co-glycolide acid (PLGA) in drug delivery. Ann Pharm Fr. 2022;80(5):603–616. https://doi.org/10.1016/j.pharma.2021.11.009
Yan J, Huang L, Feng J, Yang X. The Recent Applications of PLGA-Based Nanostructures for Ischemic Stroke. Pharmaceutics. 2023;15(9):2322. https://doi.org/10.3390/pharmaceutics15092322
Gentile P, Chiono V, Carmagnola I, Hatton PV. An Overview of Poly(lactic-co-glycolic) Acid (PLGA)-Based Biomaterials for Bone Tissue Engineering. Int J Mol Sci. 2014;15(3):3640–3659. https://doi.org/10.3390/ijms15033640
Garner J, Skidmore S, Hadar J, Park H, Park K, Kuk Jhon Y, Qin B, Wang Y. Analysis of semi-solvent effects for PLGA polymers. Int J Pharm. 2021;602:120627. https://doi.org/10.1016/j.ijpharm.2021.120627
Butreddy A, Gaddam RP, Kommineni N, Dudhipala N, Voshavar C. PLGA/PLA-Based Long-Acting Injectable Depot Microspheres in Clinical Use: Production and Characterization Overview for Protein/Peptide Delivery. Int J Mol Sci. 2021;22(16):8884. https://doi.org/10.3390/ijms22168884
Operti MC, Bernhardt A, Grimm S, Engel A, Figdor CG, Tagit O. PLGA-based nanomedicines manufacturing: Technologies overview and challenges in industrial scale-up. Int J Pharm. 2021;605:120807. https://doi.org/10.1016/j.ijpharm.2021.120807
Singh S, Singha P. Effect of Modifications in Poly (Lactide-co-Glycolide) (PLGA) on Drug Release and Degradation Characteristics: A Mini Review. Curr Drug Deliv. 2021;18(10):1378–1390. https://doi.org/10.2174/1567201818666210510165938
Kim G, Gavande V, Shaikh V, Lee WK. Degradation Behavior of Poly(Lactide-Co-Glycolide) Monolayers Investigated by Langmuir Technique: Accelerating Effect. Molecules. 2023;28(12):4810. https://doi.org/10.3390/molecules28124810
Smith AN, Ulsh JB, Gupta R, Tang MM, Peredo AP, Teinturier TD, Mauck RL, Gullbrand S, Hast MW. Characterization of degradation kinetics of additively manufactured PLGA under variable mechanical loading paradigms. J Mech Behav Biomed Mater. 2024;153:106457. https://doi.org/10.1016/j.jmbbm.2024.106457
Schoubben A, Ricci M, Giovagnoli S. Meeting the unmet: from traditional to cutting-edge techniques for poly lactide and poly lactide-co-glycolide microparticle manufacturing. J Pharm Investig. 2019;49(4):381–404.
Zhang C, Yang L, Wan F, Bera H, Cun D, Rantanen J, Yang M. Quality by design thinking in the development of long-acting injectable PLGA/PLA-based microspheres for peptide and protein drug delivery. Int J Pharm. 2020;585:119441. https://doi.org/10.1016/j.ijpharm.2020.119441
Simões MF, Pinto RMA, Simões S. Hot-melt extrusion in the pharmaceutical industry: toward filing a new drug application. Drug Discov Today. 2019;24(9):1749–1768. https://doi.org/10.1016/j.drudis.2019.05.013
Park K, Skidmore S, Hadar J, Garner J, Park H, Otte A, Soh BK, Yoon G, Yu D, Yun Y, Lee BK, Jiang X, Wang Y. Injectable, long-acting PLGA formulations: Analyzing PLGA and understanding microparticle formation. J Control Release. 2019;304:125–134. https://doi.org/10.1016/j.jconrel.2019.05.003
Wan F, Yang M. Design of PLGA-based depot delivery systems for biopharmaceuticals prepared by spray drying. Int J Pharm. 2016;498(1-2):82–95. https://doi.org/10.1016/j.ijpharm.2015.12.025
Jarvis BP, Holtyn AF, Subramaniam S, Tompkins DA, Oga EA, Bigelow GE, Silverman K. Extended-release injectable naltrexone for opioid use disorder: a systematic review. Addiction. 2018;113(7):1188–1209. https://doi.org/10.1111/add.14180
Pellegrini GABP, Bordon AF, Allemann N. Intravitreal dexamethasone implant (Ozurdex®) findings over time: ultrasound and ultra-widefield fundus photography. Int J Retina Vitreous. 2025;11(1):7. https://doi.org/10.1186/s40942-024-00625-6
Genovese S, Mannucci E, Ceriello A. A Review of the Long-Term Efficacy, Tolerability, and Safety of Exenatide Once Weekly for Type 2 Diabetes. Adv Ther. 2017;34(8):1791–1814. https://doi.org/10.1007/s12325-017-0499-6
Soliman AM, Bonafede M, Farr AM, Castelli-Haley J, Winkel C. Analysis of Adherence, Persistence, and Surgery Among Endometriosis Patients Treated with Leuprolide Acetate Plus Norethindrone Acetate Add-Back Therapy. J Manag Care Spec Pharm. 2016;22(5):573–587. https://doi.org/10.18553/jmcp.2016.22.5.573
Lim YW, Tan WS, Ho KL, Mariatulqabtiah AR, Abu Kasim NH, Abd Rahman N, Wong TW, Chee CF. Challenges and Complications of Poly(lactic-co-glycolic acid)-Based Long-Acting Drug Product Development. Pharmaceutics. 2022;14(3):614. https://doi.org/10.3390/pharmaceutics14030614
Paik J, Duggan ST, Keam SJ. Triamcinolone Acetonide Extended-Release: A Review in Osteoarthritis Pain of the Knee. Drugs. 2019;79(4):455–462. https://doi.org/10.1007/s40265-019-01083-3
Ramage M, Bishop B, Mangano V, Mankabady B. Monthly buprenorphine depot injection (SUBLOCADE®) for opioid use disorder during pregnancy. Am J Addict. 2025;34(5):485–494. https://doi.org/10.1111/ajad.70034
Kern RC, Stolovitzky JP, Silvers SL, Singh A, Lee JT, Yen DM, Iloreta AMC Jr, Langford FPJ, Karanfilov B, Matheny KE, Stambaugh JW, Gawlicka AK, RESOLVE II study investigators. A phase 3 trial of mometasone furoate sinus implants for chronic sinusitis with recurrent nasal polyps. Int Forum Allergy Rhinol. 2018;8(4):471–481. https://doi.org/10.1002/alr.22084
Popovic J, Geffner ME, Rogol AD, Silverman LA, Kaplowitz PB, Mauras N, Zeitler P, Eugster EA, Klein KO. Gonadotropin-releasing hormone analog therapies for children with central precocious puberty in the United States. Front Pediatr. 2022;10:968485. https://doi.org/10.3389/fped.2022.968485
Smishko RO, Lyzhniuk VV. Development of a technology for a pharmaceutical composition with prolonged release of the antihistamine active pharmaceutical ingredient desloratadine. Farmatsevtychnyi Zhurnal. 2025;(2):64–77. https://doi.org/10.32352/0367-3057.2.25.06 [in Ukrainian].
Hua Y, Su Y, Zhang H, et al. Poly(lactic-co-glycolic acid) microsphere production based on quality by design: a review. Drug Deliv. 2021;28(1):1342-1355. https://doi.org/10.1080/10717544.2021.1943056
Lavelle EC, Yeh MK, Coombes AG, Davis SS. The stability and immunogenicity of a protein antigen encapsulated in biodegradable microparticles based on blends of lactide polymers and polyethylene glycol. Vaccine. 1999;17:512–529. https://doi.org/10.1016/S0264-410X(98)00229-1
Muddineti OS, Omri A. Current trends in PLGA based long-acting injectable products: The industry perspective. Expert Opin Drug Deliv. 2022;19(5):559–576. https://doi.org/10.1080/17425247.2022.2075845
Kim SM, Patel M, Patel R. PLGA Core-Shell Nano/Microparticle Delivery System for Biomedical Application. Polymers. 2021;13(20):3471. https://doi.org/10.3390/polym13203471
Han FY, Thurecht KJ, Whittaker AK, Smith MT. Bioerodable PLGA-Based Microparticles for Producing Sustained-Release Drug Formulations and Strategies for Improving Drug Loading. Front Pharmacol. 2016;7:185. https://doi.org/10.3389/fphar.2016.00185
Lagreca E, Onesto V, Di Natale C, La Manna S, Netti PA, Vecchione R. Recent advances in the formulation of PLGA microparticles for controlled drug delivery. Prog Biomater. 2020;9(4):153–174. https://doi.org/10.1007/s40204-020-00139-y
Ramazani F, Chen W, van Nostrum CF, Storm G, Kiessling F, Lammers T, Hennink WE, Kok RJ. Strategies for encapsulation of small hydrophilic and amphiphilic drugs in PLGA microspheres: State-of-the-art and challenges. Int J Pharm. 2016;499(1-2):358–367. https://doi.org/10.1016/j.ijpharm.2016.01.020
Hu L, Zhang H, Song W. An overview of preparation and evaluation sustained-release injectable microspheres. J Microencapsul. 2013;30(4):369–382. https://doi.org/10.3109/02652048.2012.742158
El-Hammadi MM, Arias JL. Recent Advances in the Surface Functionalization of PLGA-Based Nanomedicines. Nanomaterials. 2022;12(3):354. https://doi.org/10.3390/nano12030354
Ye M, Kim S, Park K. Issues in long-term protein delivery using biodegradable microparticles. J Control Release. 2010;146(2):241–260. https://doi.org/10.1016/j.jconrel.2010.05.011
Giles MB, Hong JKY, Liu Y, et al. Efficient aqueous remote loading of peptides in poly(lactic-co-glycolic acid). Nat Commun. 2022;13:3282. https://doi.org/10.1038/s41467-022-30813-7
Wan F, Yang M. Design of PLGA-based depot delivery systems for biopharmaceuticals prepared by spray drying. Int J Pharm. 2016;498(1-2):82–95. https://doi.org/10.1016/j.ijpharm.2015.12.025
Jensen DM, Cun D, Maltesen MJ, Frokjaer S, Nielsen HM, Foged C. Spray drying of siRNA-containing PLGA nanoparticles intended for inhalation. J Control Release. 2010;142(1):138–145. https://doi.org/10.1016/j.jconrel.2009.10.010
Ding D, Zhu Q. Recent advances of PLGA micro/nanoparticles for the delivery of biomacromolecular therapeutics. Mater Sci Eng C. 2018;92:1041–1060. https://doi.org/10.1016/j.msec.2017.12.036
Badens E, Masmoudi Y, Mouahid A, Crampon C. Current situation and perspectives in drug formulation by using supercritical fluid technology. J Supercrit Fluids. 2018;134:274–283. https://doi.org/10.1016/j.supflu.2017.12.038
Champeau M, Thomassin JM, Tassaing T, Jérôme C. Drug loading of polymer implants by supercritical CO₂ assisted impregnation: A review. J Control Release. 2015;209:248–259. https://doi.org/10.1016/j.jconrel.2015.05.002
Gangapurwala G, Vollrath A, De San Luis A, Schubert US. PLA/PLGA-Based Drug Delivery Systems Produced with Supercritical CO₂—A Green Future for Particle Formulation? Pharmaceutics. 2020;12(11):1118. https://doi.org/10.3390/pharmaceutics12111118
Rezvantalab S, Keshavarz Moraveji M. Microfluidic assisted synthesis of PLGA drug delivery systems. RSC Adv. 2019;9(4):2055-2072. https://doi.org/10.1039/c8ra08972h
Zhao P, Wang J, Chen C, Wang J, Liu G, Nandakumar K, Li Y, Wang L. Microfluidic Applications in Drug Development: Fabrication of Drug Carriers and Drug Toxicity Screening. Micromachines. 2022;13(2):200. https://doi.org/10.3390/mi13020200
Omidian H, Wilson RL. PLGA Implants for Controlled Drug Delivery and Regenerative Medicine: Advances, Challenges, and Clinical Potential. Pharmaceuticals. 2025;18(5):631. https://doi.org/10.3390/ph1805063151
Li Z, Mu H, Larsen SW, Jensen H, Østergaard J. An in vitro gel-based system for characterizing and predicting the long-term performance of PLGA in situ forming implants. Int J Pharm. 2021;609:121183. https://doi.org/10.1016/j.ijpharm.2021.121183
Amini-Fazl MS. Biodegradation study of PLGA as an injectable in situ depot-forming implant for controlled release of paclitaxel. Polym. Bull. 2022;79:2763–2776. https://doi.org/10.1007/s00289-020-03347-5
Parent M, Nouvel C, Koerber M, Sapin A, Maincent P, Boudier A. PLGA in situ implants formed by phase inversion: critical physicochemical parameters to modulate drug release. J Control Release. 2013;172(1):292–304. https://doi.org/10.1016/j.jconrel.2013.08.024
Lim YW, Tan WS, Ho KL, Mariatulqabtiah AR, Abu Kasim NH, Abd Rahman N, Wong TW, Chee CF. Challenges and Complications of Poly(lactic-co-glycolic acid)-Based Long-Acting Drug Product Development. Pharmaceutics. 2022;14(3):614. https://doi.org/10.3390/pharmaceutics14030614
Wan B, Andhariya JV, Bao Q, Wang Y, Zou Y, Burgess DJ. Effect of polymer source on in vitro drug release from PLGA microspheres. Int J Pharm. 2021;607:120907. https://doi.org/10.1016/j.ijpharm.2021.120907
Hernandez C, Gawlik N, Goss M, Zhou H, Jeganathan S, Gilbert D, Exner AA. Macroporous acrylamide phantoms improve prediction of in vivo performance of in situ forming implants. J Control Release. 2016;243:225–231. https://doi.org/10.1016/j.jconrel.2016.10.009
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