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Cited by 42Nanoparticle-Based Drug DeliveryAdvanced Drug Delivery SystemsRNA Interference and Gene Delivery

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PLGA-Based Co-Delivery Nanoformulations: Overview, Strategies, and Recent Advances

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Stevanović, Magdalena M., Qian, Kun, Huang, Lin, Vukomanović, Marija·2025·Pharmaceutics
DOI 10.3390/pharmaceutics17121613PMC PMC12736669
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Abstract

Poly (lactic-co-glycolic acid) (PLGA) is a widely used copolymer with applications across medical, pharmaceutical, and other industrial fields. Its biodegradability and biocompatibility make it one of the most versatile polymers for nanoscale drug delivery. The present review addresses current knowledge and recent advances in PLGA-based co-delivery nanoformulations with a special reference to design strategies, functional mechanisms, and translational potential. Conventional and advanced fabrication methods, the structural design of PLGA-based nanocarriers, approaches to scale-up and reproducibility, classification of co-delivery types, mechanisms governing drug release, surface modification and functionalization are all discussed. Special attention is given to PLGA-based co-delivery systems, encompassing drug–drug, drug–gene, gene–gene and multi-modal combinations, supported by recent studies demonstrating synergistic therapeutic outcomes. The review also examines clinical translation efforts and the regulatory landscape for PLGA-based nanocarriers. Unlike most existing reviews that typically focus either on PLGA fundamentals or on co-delivery approaches in isolation, this article bridges these domains by providing an integrated, comparative analysis of PLGA-based co-delivery systems and elucidating a critical gap in linking design strategies with translational requirements. In addition, by emphasising the relevance of PLGA-based co-delivery for combination therapies, particularly in cancer and other complex diseases, the review highlights the strong clinical and translational potential of these platforms. Key challenges, such as reproducibility, large-scale manufacturing, and complex regulatory pathways, are discussed alongside emerging trends and future perspectives. Taken together, this review positions PLGA-based co-delivery strategies as a critical driver for advancing precision therapeutics and shaping the future landscape of nanomedicine.

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  1. Adepu, S., and Ramakrishna, S. (2021). Controlled Drug Delivery Systems: Current Status and Future Directions. Molecules, 26. · DOI
  2. Zhu, Y., He, M., Lin, C., Ma, W., Ai, Y., Wang, J., and Liang, Q. (2025). Multifunctional Nanocarrier Drug Delivery Systems: From Diverse Design to Precise Biomedical Applications. Adv. Healthc. Mater., e02178. · DOI
  3. Kim, 2025, Progress in Cancer Vaccines Enabled by Nanotechnology, Nat. Nanotechnol., 20, 1558, 10.1038/s41565-025-02021-z · DOI
  4. Stevanović, M., and Filipović, N. (2024). A Review of Recent Developments in Biopolymer Nano-Based Drug Delivery Systems with Antioxidative Properties: Insights into the Last Five Years. Pharmaceutics, 16. · DOI
  5. Makadia, 2011, Poly Lactic-Co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier, Polymers, 3, 1377, 10.3390/polym3031377 · DOI · Paper page
  6. 2012, Poly(Lactide-Co-Glycolide)/Silver Nanoparticles: Synthesis, Characterization, Antimicrobial Activity, Cytotoxicity Assessment and ROS-Inducing Potential, Polymer, 53, 2818, 10.1016/j.polymer.2012.04.057 · DOI
  7. Stupar, 2014, Development of Lyophilized Spherical Particles of Poly(Epsilon- Caprolactone) and Examination of Their Morphology, Cytocompatibility and Influence on the Formation of Reactive Oxygen Species, J. Drug Deliv. Sci. Technol., 24, 191, 10.1016/S1773-2247(14)50031-7 · DOI
  8. Antonara, L., Triantafyllopoulou, E., Chountoulesi, M., Pippa, N., Dallas, P.P., and Rekkas, D.M. (2025). Lipid-Based Drug Delivery Systems: Concepts and Recent Advances in Transdermal Applications. Nanomaterials, 15. · DOI
  9. Zhang, 2025, An Antibacterial Sensitive Wearable Biosensor Enabled by Engineered Metal-Boride-Based Organic Electrochemical Transistors and Hydrogel Microneedles, J. Mater. Chem. A, 13, 18590, 10.1039/D5TA01335F · DOI
  10. Li, 2023, Emerging Biosensors Based on Noble Metal Self-Assembly for In Vitro Disease Diagnosis, Adv. NanoBiomed Res., 3, 2200148, 10.1002/anbr.202200148 · DOI
  11. Yang, 2022, Defective Fe Metal–Organic Frameworks Enhance Metabolic Profiling for High-Accuracy Diagnosis of Human Cancers, Adv. Mater., 34, 2201422, 10.1002/adma.202201422 · DOI
  12. Boccaccini, 2015, 45S5Bioglass®-Based Scaffolds Coated with Selenium Nanoparticles or with Poly(Lactide-Co-Glycolide)/Selenium Particles: Processing, Evaluation and Antibacterial Activity, Colloids Surf. B Biointerfaces, 132, 208, 10.1016/j.colsurfb.2015.05.024 · DOI
  13. Stevanović, M. (2019). Biomedical Applications of Nanostructured Polymeric Materials. Nanostructured Polymer Composites for Biomedical Applications, Elsevier. · DOI
  14. Liu, 2022, Porous Inorganic Materials for Bioanalysis and Diagnostic Applications, ACS Biomater. Sci. Eng., 8, 4092, 10.1021/acsbiomaterials.1c00733 · DOI
  15. Unnikrishnan, 2023, Exploration of Inorganic Nanoparticles for Revolutionary Drug Delivery Applications: A Critical Review, Discov. Nano, 18, 157, 10.1186/s11671-023-03943-0 · DOI
  16. Asad, 2022, Inorganic Nanoparticles for Oral Drug Delivery: Opportunities, Barriers, and Future Perspectives, Curr. Opin. Chem. Eng., 38, 100869, 10.1016/j.coche.2022.100869 · DOI
  17. Bao, 2025, A Dataset on Formulation Parameters and Characteristics of Drug-Loaded PLGA Microparticles, Sci. Data, 12, 364, 10.1038/s41597-025-04621-9 · DOI
  18. Maksin, 2009, An Innovative, Quick and Convenient Labeling Method for the Investigation of Pharmacological Behavior and the Metabolism of Poly(DL-Lactide-Co-Glycolide) Nanospheres, Nanotechnology, 20, 335102, 10.1088/0957-4484/20/33/335102 · DOI
  19. Pandey, 2025, An Updated Review Summarizing the Anticancer Potential of Poly(Lactic- Co -Glycolic Acid) (PLGA) Based Curcumin, Epigallocatechin Gallate, and Resveratrol Nanocarriers, Biopolymers, 116, e23637, 10.1002/bip.23637 · DOI
  20. 2011, ROS-Inducing Potential, Influence of Different Porogens and in Vitro Degradation of Poly (D,L-Lactide-Co-Glycolide)-Based Material, Express Polym. Lett., 5, 996, 10.3144/expresspolymlett.2011.97 · DOI
  21. Maksin, 2011, Poly(d,l-Lactide-Co-Glycolide)/Hydroxyapatite Core-Shell Nanospheres. Part 1: A Multifunctional System for Controlled Drug Delivery, Colloids Surf. B Biointerfaces, 82, 404, 10.1016/j.colsurfb.2010.09.011 · DOI
  22. Kralj, 2011, Poly(D,L-Lactide-Co-Glycolide)/Hydroxyapatite Core–Shell Nanosphere. Part 2: Simultaneous Release of a Drug and a Prodrug (Clindamycin and Clindamycin Phosphate), Colloids Surf. B Biointerfaces, 82, 414, 10.1016/j.colsurfb.2010.09.012 · DOI
  23. 2011, Poly(d,l-Lactide-Co-Glycolide)/Hydroxyapatite Core–Shell Nanospheres. Part 3: Properties of Hydroxyapatite Nano-Rods and Investigation of a Distribution of the Drug within the Composite, Colloids Surf. B Biointerfaces, 87, 226, 10.1016/j.colsurfb.2011.05.023 · DOI
  24. Chen, D., Liu, X., Lu, X., and Tian, J. (2023). Nanoparticle Drug Delivery Systems for Synergistic Delivery of Tumor Therapy. Front. Pharmacol., 14. · DOI
  25. Li, M., Sun, X., Yin, M., Shen, J., and Yan, S. (2023). Recent Advances in Nanoparticle-Mediated Co-Delivery System: A Promising Strategy in Medical and Agricultural Field. Int. J. Mol. Sci., 24. · DOI
  26. Li, 2024, Multifunctional Nanoparticle-Mediated Combining Therapy for Human Diseases, Signal Transduct. Target. Ther., 9, 1, 10.1038/s41392-023-01668-1 · DOI
  27. Punnakitikashem, 2021, PLGA Nanoparticles Containing α-Fetoprotein SiRNA Induce Apoptosis and Enhance the Cytotoxic Effects of Doxorubicin in Human Liver Cancer Cell Line, Biochem. Biophys. Res. Commun., 553, 191, 10.1016/j.bbrc.2021.03.086 · DOI
  28. Chen, Z., Zhang, X., Fu, Y., Jin, Y., Weng, Y., Bian, X., and Chen, X. (2024). Degradation Behaviors of Polylactic Acid, Polyglycolic Acid, and Their Copolymer Films in Simulated Marine Environments. Polymers, 16. · DOI
  29. Lee, J.W., Park, J.H., Yu, G.W., You, J.W., Han, M.J., Kang, M.J., and Ho, M.J. (2025). Sustained-Release Intra-Articular Drug Delivery: PLGA Systems in Clinical Context and Evolving Strategies. Pharmaceutics, 17. · DOI
  30. Kost, 2022, The Influence of the Functional End Groups on the Properties of Polylactide-Based Materials, Prog. Polym. Sci., 130, 101556, 10.1016/j.progpolymsci.2022.101556 · DOI
  31. Yang, J., Zeng, H., Luo, Y., Chen, Y., Wang, M., Wu, C., and Hu, P. (2024). Recent Applications of PLGA in Drug Delivery Systems. Polymers, 16. · DOI · Paper page
  32. Li, Y., Tao, T., Xiong, Y., Guo, W., and Liang, Y. (2025). Multifunctional PLGA Nanosystems: Enabling Integrated Diagnostic and Therapeutic Strategies. Front. Pharmacol., 16. · DOI
  33. Lehner, 2025, Enhancing Drug Release from PEG-PLGA Implants: The Role of Hydrophilic Dexamethasone Phosphate in Modulating Release Kinetics and Degradation Behavior, Eur. J. Pharm. Sci., 209, 107067, 10.1016/j.ejps.2025.107067 · DOI
  34. Eltaib, L. (2025). Polymeric Nanoparticles in Targeted Drug Delivery: Unveiling the Impact of Polymer Characterization and Fabrication. Polymers, 17. · DOI
  35. Omidian, H., Wilson, R.L., and Castejon, A.M. (2025). Recent Advances in Peptide-Loaded PLGA Nanocarriers for Drug Delivery and Regenerative Medicine. Pharmaceuticals, 18. · DOI
  36. Bachta, 2025, A Comprehensive Study on PH-Sensitive Nanoparticles for the Efficient Delivery of Drugs, J. Adv. Biotechnol. Exp. Ther., 8, 200, 10.5455/jabet.2025.17 · DOI
  37. Ge, 2025, Research Progress of Sustained-Release Microsphere Technology in Drug Delivery, Eur. J. Med. Chem. Rep., 15, 100299
  38. Nagaraj, 2025, State-of-the-Art Surfactants as Biomedical Game Changers: Unlocking Their Potential in Drug Delivery, Diagnostics, and Tissue Engineering, Int. J. Pharm., 676, 125590, 10.1016/j.ijpharm.2025.125590 · DOI
  39. Costa, 2025, Exploring the Potential of PLGA Nanoparticles for Enhancing Pulmonary Drug Delivery, Mol. Pharm., 22, 3542, 10.1021/acs.molpharmaceut.5c00118 · DOI
  40. Boudoukhani, M., Yahoum, M.M., Ezzroug, K., Toumi, S., Lefnaoui, S., Moulai-Mostefa, N., Sid, A.N.E.H., Tahraoui, H., Kebir, M., and Amrane, A. (2024). Formulation and Characterization of Double Emulsions W/O/W Stabilized by Two Natural Polymers with Two Manufacturing Processes (Comparative Study). ChemEngineering, 8. · DOI
  41. Kozalak, G., Heyat Davoudian, S., Natsaridis, E., Gogniat, N., Koşar, A., and Tagit, O. (2025). Optimization of PLGA Nanoparticle Formulation via Microfluidic and Batch Nanoprecipitation Techniques. Micromachines, 16. · DOI
  42. Chen, 2025, Spray Drying Strategies for the Construction of Drug-Loaded Particles: Insights into Design Principles and Pharmaceutical Applications, Int. J. Pharm., 682, 125917, 10.1016/j.ijpharm.2025.125917 · DOI
  43. Vinchhi, P., Patel, J.K., and Patel, M.M. (2021). High-Pressure Homogenization Techniques for Nanoparticles. Emerging Technologies for Nanoparticle Manufacturing, Springer International Publishing. · DOI
  44. Izutsu, K. (2018). Applications of Freezing and Freeze-Drying in Pharmaceutical Formulations. Survival Strategies in Extreme Cold and Desiccation, Springer. · DOI
  45. Alkholief, M., Kalam, M.A., Anwer, M.K., and Alshamsan, A. (2022). Effect of Solvents, Stabilizers and the Concentration of Stabilizers on the Physical Properties of Poly(d,l-Lactide-Co-Glycolide) Nanoparticles: Encapsulation, In Vitro Release of Indomethacin and Cytotoxicity against HepG2-Cell. Pharmaceutics, 14. · DOI
  46. Park, H. (2024). Exploring the Effects of Process Parameters during W/O/W Emulsion Preparation and Supercritical Fluid Extraction on the Protein Encapsulation and Release Properties of PLGA Microspheres. Pharmaceutics, 16. · DOI
  47. Sanderson, 2004, The Role of Surfactant in Controlling Particle Size and Stability in the Miniemulsion Polymerization of Polymeric Nanocapsules, Eur. Polym. J., 40, 2717, 10.1016/j.eurpolymj.2004.07.021 · DOI
  48. Chiesa, 2022, Development and optimization of microfluidic assisted manufacturing process to produce PLGA nanoparticles, Int. J. Pharm., 629, 122368, 10.1016/j.ijpharm.2022.122368 · DOI
  49. 2025, Advanced Microfluidic Techniques for the Preparation of Solid Lipid Nanoparticles: Innovations and Biomedical Applications, Int. J. Pharm. X, 10, 100399
  50. Park, H., Kim, J.-S., Kim, S., Ha, E.-S., Kim, M.-S., and Hwang, S.-J. (2021). Pharmaceutical Applications of Supercritical Fluid Extraction of Emulsions for Micro-/Nanoparticle Formation. Pharmaceutics, 13. · DOI
  51. Patel, 2024, Review on Electrospray Nanoparticles for Drug Delivery: Exploring Applications, Polym. Adv. Technol., 35, e6507, 10.1002/pat.6507 · DOI
  52. Lau, 2025, Advancements in 3D-Printing Strategies towards Developing Effective Implantable Drug Delivery Systems: Recent Applications and Opportunities, Adv. Drug Deliv. Rev., 227, 115711, 10.1016/j.addr.2025.115711 · DOI
  53. 2020, PLGA Nanoparticle Preparations by Emulsification and Nanoprecipitation Techniques: Effects of Formulation Parameters, RSC Adv., 10, 4218, 10.1039/C9RA10857B · DOI
  54. del Castillo-Santaella, T., Ortega-Oller, I., Padial-Molina, M., O’Valle, F., Galindo-Moreno, P., Jódar-Reyes, A.B., and Peula-García, J.M. (2019). Formulation, Colloidal Characterization, and In Vitro Biological Effect of BMP-2 Loaded PLGA Nanoparticles for Bone Regeneration. Pharmaceutics, 11. · DOI
  55. Ghaly, 2025, Enhanced Nanoprecipitation Method for the Production of PLGA Nanoparticles for Oncology Applications, AAPS J., 27, 113, 10.1208/s12248-025-01096-9 · DOI
  56. Neustrup, 2024, A Versatile, Low-Cost Modular Microfluidic System to Prepare Poly(Lactic-Co-Glycolic Acid) Nanoparticles With Encapsulated Protein, Pharm. Res., 41, 2347, 10.1007/s11095-024-03792-1 · DOI
  57. Udepurkar, 2024, Microfluidic Synthesis of PLGA Nanoparticles Enabled by an Ultrasonic Microreactor, React. Chem. Eng., 9, 2208, 10.1039/D4RE00107A · DOI
  58. Omidian, H., and Wilson, R.L. (2025). PLGA Implants for Controlled Drug Delivery and Regenerative Medicine: Advances, Challenges, and Clinical Potential. Pharmaceuticals, 18. · DOI
  59. Wang, 2025, Constrained Composite Bayesian Optimization for Rational Synthesis of Polymeric Particles, Digit. Discov., 4, 3066, 10.1039/D5DD00243E · DOI
  60. Kurul, 2025, Nanomedicine: How Nanomaterials Are Transforming Drug Delivery, Bio-Imaging, and Diagnosis, Next Nanotechnol., 7, 100129, 10.1016/j.nxnano.2024.100129 · DOI
  61. Klojdová, I., Milota, T., Smetanová, J., and Stathopoulos, C. (2023). Encapsulation: A Strategy to Deliver Therapeutics and Bioactive Compounds?. Pharmaceuticals, 16. · DOI
  62. Morker, 2025, Comprehensive Review on the Stability and Degradation of Polysorbates in Biopharmaceuticals, EJPPS Eur. J. Parenter. Pharm. Sci., 30, 3
  63. Cortés, H., Hernández-Parra, H., Bernal-Chávez, S.A., Del Prado-Audelo, M.L., Caballero-Florán, I.H., Borbolla-Jiménez, F.V., González-Torres, M., Magaña, J.J., and Leyva-Gómez, G. (2021). Non-Ionic Surfactants for Stabilization of Polymeric Nanoparticles for Biomedical Uses. Materials, 14. · DOI
  64. Stevanović, M. (2017). Polymeric Micro- and Nanoparticles for Controlled and Targeted Drug Delivery. Nanostructures for Drug Delivery, Elsevier. · DOI
  65. Stevanovic, 2007, Preparation and Characterization of Poly(D,L-Lactide-Co-Glycolide) Nanoparticles Containing Ascorbic Acid, BioMed Res. Int., 2007, 084965
  66. Goracinova, K., Geskovski, N., Dimchevska, S., Li, X., and Gref, R. (2018). Multifunctional Core–Shell Polymeric and Hybrid Nanoparticles as Anticancer Nanomedicines. Design of Nanostructures for Theranostics Applications, Elsevier. · DOI
  67. Zhang, 2021, Janus Nanoparticles: From Fabrication to (Bio)Applications, ACS Nano, 15, 6147, 10.1021/acsnano.1c01146 · DOI
  68. Hassan, A.A.A., Ramadan, E., Kristó, K., Regdon, G., and Sovány, T. (2025). Lipid-Polymer Hybrid Nanoparticles as a Smart Drug Delivery System for Peptide/Protein Delivery. Pharmaceutics, 17. · DOI
  69. Zafar, A., Takeda, C., Manzoor, A., Tanaka, D., Kobayashi, M., Wadayama, Y., Nakane, D., Majeed, A., Iqbal, M.A., and Akitsu, T. (2024). Towards Industrially Important Applications of Enhanced Organic Reactions by Microfluidic Systems. Molecules, 29. · DOI
  70. Gurba-Bryśkiewicz, L., Maruszak, W., Smuga, D.A., Dubiel, K., and Wieczorek, M. (2023). Quality by Design (QbD) and Design of Experiments (DOE) as a Strategy for Tuning Lipid Nanoparticle Formulations for RNA Delivery. Biomedicines, 11. · DOI
  71. Deepika, 2019, Dual Drug Loaded PLGA Nanospheres for Synergistic Efficacy in Breast Cancer Therapy, Mater. Sci. Eng. C, 103, 109716, 10.1016/j.msec.2019.05.001 · DOI
  72. Rahman, 2024, Nanocarriers for Delivering Nucleic Acids and Chemotherapeutic Agents as Combinational Approach: Challenges, Clinical Progress, and Unmet Needs, J. Drug Deliv. Sci. Technol., 92, 105326, 10.1016/j.jddst.2023.105326 · DOI
  73. Yao, Y., Zhou, Y., Liu, L., Xu, Y., Chen, Q., Wang, Y., Wu, S., Deng, Y., Zhang, J., and Shao, A. (2020). Nanoparticle-Based Drug Delivery in Cancer Therapy and Its Role in Overcoming Drug Resistance. Front. Mol. Biosci., 7. · DOI
  74. Gao, Y., Zhu, Y., Xu, X., Wang, F., Shen, W., Leng, X., Zhao, J., Liu, B., Wang, Y., and Liu, P. (2021). Surface PEGylated Cancer Cell Membrane-Coated Nanoparticles for Codelivery of Curcumin and Doxorubicin for the Treatment of Multidrug Resistant Esophageal Carcinoma. Front. Cell Dev. Biol., 9. · DOI
  75. Altanam, S.Y., Darwish, N., and Bakillah, A. (2025). Exploring the Interplay of Antioxidants, Inflammation, and Oxidative Stress: Mechanisms, Therapeutic Potential, and Clinical Implications. Diseases, 13. · DOI
  76. Pillai, S.C., Borah, A., Le, M.N.T., Kawano, H., Hasegawa, K., and Kumar, D.S. (2021). Co-Delivery of Curcumin and Bioperine via PLGA Nanoparticles to Prevent Atherosclerotic Foam Cell Formation. Pharmaceutics, 13. · DOI
  77. Lim, Y.W., Tan, W.S., Ho, K.L., Mariatulqabtiah, A.R., Abu Kasim, N.H., Abd. Rahman, N., Wong, T.W., and Chee, C.F. (2022). Challenges and Complications of Poly(Lactic-Co-Glycolic Acid)-Based Long-Acting Drug Product Development. Pharmaceutics, 14. · DOI
  78. Sousa, C., and Videira, M. (2025). Dual Approaches in Oncology: The Promise of SiRNA and Chemotherapy Combinations in Cancer Therapies. Onco, 5. · DOI
  79. Ashrafizadeh, 2020, Progress in Natural Compounds/SiRNA Co-Delivery Employing Nanovehicles for Cancer Therapy, ACS Comb. Sci., 22, 669, 10.1021/acscombsci.0c00099 · DOI
  80. Lin, 2024, Optimization of Lipid Assisted Polymeric Nanoparticles for SiRNA Delivery and Cancer Immunotherapy, Biomater. Sci., 12, 2057, 10.1039/D3BM02071A · DOI
  81. Liang, 2024, SiRNA/CS-PLGA Nanoparticle System Targeting Knockdown Intestinal SOAT2 Reduced Intestinal Lipid Uptake and Alleviated Obesity, Adv. Sci., 11, 2403442, 10.1002/advs.202403442 · DOI
  82. Moazzam, 2024, The Landscape of Nanoparticle-Based SiRNA Delivery and Therapeutic Development, Mol. Ther., 32, 284, 10.1016/j.ymthe.2024.01.005 · DOI · Paper page
  83. Lahan, 2024, Multifunctional Approach with LHRH-Mediated PLGA Nanoconjugate for Site-Specific Codelivery of Curcumin and BCL2 SiRNA in Mice Lung Cancer, Future J. Pharm. Sci., 10, 163, 10.1186/s43094-024-00743-w · DOI
  84. Chen, L., Luo, J., Zhang, J., Wang, S., Sun, Y., Liu, Q., and Cheng, C. (2023). Dual Targeted Nanoparticles for the Codelivery of Doxorubicin and SiRNA Cocktails to Overcome Ovarian Cancer Stem Cells. Int. J. Mol. Sci., 24. · DOI
  85. Sanati, 2024, Bioengineered Nanomaterials for SiRNA Therapy of Chemoresistant Cancers, ACS Nano, 18, 34425, 10.1021/acsnano.4c11259 · DOI
  86. Cavazza, 2025, Advanced Delivery Systems for Gene Editing: A Comprehensive Review from the GenE-HumDi COST Action Working Group, Mol. Ther. Nucleic Acids, 36, 102457, 10.1016/j.omtn.2025.102457 · DOI
  87. Hong, 2024, Highly Efficient Nucleic Acid Encapsulation Method for Targeted Gene Therapy Using Antibody Conjugation System, Mol. Ther. Nucleic Acids, 35, 102322, 10.1016/j.omtn.2024.102322 · DOI
  88. Fatima, 2023, Engineering SiRNA Therapeutics: Challenges and Strategies, J. Nanobiotechnol., 21, 381, 10.1186/s12951-023-02147-z · DOI
  89. Dubey, A.K., and Mostafavi, E. (2023). Biomaterials-Mediated CRISPR/Cas9 Delivery: Recent Challenges and Opportunities in Gene Therapy. Front. Chem., 11. · DOI
  90. Kaupbayeva, B., Tsoy, A., Safarova, Y., Nurmagambetova, A., Murata, H., Matyjaszewski, K., and Askarova, S. (2024). Unlocking Genome Editing: Advances and Obstacles in CRISPR/Cas Delivery Technologies. J. Funct. Biomater., 15. · DOI
  91. Wang, 2022, Multifunctional Microcapsules: A Theranostic Agent for US/MR/PAT Multi-Modality Imaging and Synergistic Chemo-Photothermal Osteosarcoma Therapy, Bioact. Mater., 7, 453
  92. Hassan, 2020, Biodegradable Photoresponsive Nanoparticles for Chemo-, Photothermal- and Photodynamic Therapy of Ovarian Cancer, Mater. Sci. Eng. C, 116, 111196, 10.1016/j.msec.2020.111196 · DOI
  93. Mahanta, 2025, Engineered PLGA Nanoparticles for Brain-Targeted Codelivery of Cannabidiol and PApoE2 through the Intranasal Route for the Treatment of Alzheimer’s Disease, ACS Biomater. Sci. Eng., 11, 3533, 10.1021/acsbiomaterials.5c00465 · DOI
  94. Cruz, 2021, PLGA-Nanoparticles for Intracellular Delivery of the CRISPR-Complex to Elevate Fetal Globin Expression in Erythroid Cells, Biomaterials, 268, 120580, 10.1016/j.biomaterials.2020.120580 · DOI
  95. Martins, 2020, Modelling Protein Therapeutic Co-Formulation and Co-Delivery with PLGA Nanoparticles Continuously Manufactured by Microfluidics, React. Chem. Eng., 5, 308, 10.1039/C9RE00395A · DOI
  96. Ebrahimian, 2017, Co-Delivery of Doxorubicin Encapsulated PLGA Nanoparticles and Bcl-XL ShRNA Using Alkyl-Modified PEI into Breast Cancer Cells, Appl. Biochem. Biotechnol., 183, 126, 10.1007/s12010-017-2434-3 · DOI
  97. Kesharwani, 2025, PEGylated PLGA Nanoparticles: Unlocking Advanced Strategies for Cancer Therapy, Mol. Cancer, 24, 205, 10.1186/s12943-025-02410-x · DOI · Paper page
  98. Hoover, 2013, Osteogenic and Antimicrobial Nanoparticulate Calcium Phosphate and Poly-(d,l-Lactide-Co-Glycolide) Powders for the Treatment of Osteomyelitis, Mater. Sci. Eng. C, 33, 3362, 10.1016/j.msec.2013.04.023 · DOI
  99. Rakhshani, 2025, Synergistic Effects of Doxorubicin PLGA Nanoparticles and Simvastatin Loaded in Silk Films for Local Treatment of Breast Cancer, J. Drug Deliv. Sci. Technol., 104, 106431, 10.1016/j.jddst.2024.106431 · DOI
  100. Yang, 2025, Quaternized Chitosan-Coated PLGA Nanoparticles Co-Deliver Resveratrol and All-Trans Retinoic Acid to Enhance Humoral Immunity, Cellular Immunity and Gastrointestinal Mucosal Immunity, Colloids Surf. B Biointerfaces, 256, 114994, 10.1016/j.colsurfb.2025.114994 · DOI
  101. Puricelli, C., Gigliotti, C.L., Stoppa, I., Sacchetti, S., Pantham, D., Scomparin, A., Rolla, R., Pizzimenti, S., Dianzani, U., and Boggio, E. (2023). Use of Poly Lactic-Co-Glycolic Acid Nano and Micro Particles in the Delivery of Drugs Modulating Different Phases of Inflammation. Pharmaceutics, 15. · DOI
  102. 2014, Multifunctional PLGA Particles Containing Poly(l-Glutamic Acid)-Capped Silver Nanoparticles and Ascorbic Acid with Simultaneous Antioxidative and Prolonged Antimicrobial Activity, Acta Biomater., 10, 151, 10.1016/j.actbio.2013.08.030 · DOI
  103. Li, Y., Xu, C., and Lei, C. (2023). The Delivery and Activation of Growth Factors Using Nanomaterials for Bone Repair. Pharmaceutics, 15. · DOI
  104. Lu, 2021, Co-Encapsulation of Combinatorial Flavonoids in Biodegradable Polymeric Nanoparticles for Improved Anti-Osteoporotic Activity in Ovariectomized Rats, Environ. Technol. Innov., 24, 102079, 10.1016/j.eti.2021.102079 · DOI
  105. Lee, 2012, Multifunctional Poly (Lactide-Co-Glycolide) Nanoparticles for Luminescence/Magnetic Resonance Imaging and Photodynamic Therapy, Int. J. Pharm., 434, 257, 10.1016/j.ijpharm.2012.05.068 · DOI
  106. Operti, 2021, PLGA-Based Nanomedicines Manufacturing: Technologies Overview and Challenges in Industrial Scale-Up, Int. J. Pharm., 605, 120807, 10.1016/j.ijpharm.2021.120807 · DOI · Paper page
  107. Sivadasan, D., Sultan, M.H., Madkhali, O., Almoshari, Y., and Thangavel, N. (2021). Polymeric Lipid Hybrid Nanoparticles (PLNs) as Emerging Drug Delivery Platform—A Comprehensive Review of Their Properties, Preparation Methods, and Therapeutic Applications. Pharmaceutics, 13. · DOI
  108. Gao, L., Li, J., and Song, T. (2022). Poly Lactic-Co-Glycolic Acid-Based Nanoparticles as Delivery Systems for Enhanced Cancer Immunotherapy. Front. Chem., 10. · DOI
  109. Shao, L., Shen, S., and Liu, H. (2022). Recent Advances in PLGA Micro/Nanoparticle Delivery Systems as Novel Therapeutic Approach for Drug-Resistant Tuberculosis. Front. Bioeng. Biotechnol., 10. · DOI
  110. Ghasemiyeh, P., and Mohammadi-Samani, S. (2021). Polymers Blending as Release Modulating Tool in Drug Delivery. Front. Mater., 8. · DOI
  111. 2007, Fabrication, in Vitro Degradation and the Release Behaviours of Poly(Dl-Lactide-Co-Glycolide) Nanospheres Containing Ascorbic Acid, Colloids Surf. B Biointerfaces, 59, 215, 10.1016/j.colsurfb.2007.05.011 · DOI
  112. Samanta, 2025, Effect of Mechanical Loading on PLGA Biodegradation, Polym. Degrad. Stab., 240, 111485, 10.1016/j.polymdegradstab.2025.111485 · DOI
  113. Borrelli, 2025, End Group Chemistry Modulates Physical Properties and Biomolecule Release from Biodegradable Polyesters, J. Mater. Chem. B, 13, 10621, 10.1039/D5TB00816F · DOI
  114. Bedair, 2020, Magnesium Hydroxide-Incorporated PLGA Composite Attenuates Inflammation and Promotes BMP2-Induced Bone Formation in Spinal Fusion, J. Tissue Eng., 11, 2041731420967591, 10.1177/2041731420967591 · DOI
  115. 2013, Composite PLGA/AgNpPGA/AscH Nanospheres with Combined Osteoinductive, Antioxidative, and Antimicrobial Activities, ACS Appl. Mater. Interfaces, 5, 9034, 10.1021/am402237g · DOI
  116. Ramalho, M.J., Loureiro, J.A., Coelho, M.A.N., and Pereira, M.C. (2019). Factorial Design as a Tool for the Optimization of PLGA Nanoparticles for the Co-Delivery of Temozolomide and O6-Benzylguanine. Pharmaceutics, 11. · DOI
  117. Zhu, 2015, A Mechanistic Model for Drug Release in PLGA Biodegradable Stent Coatings Coupled with Polymer Degradation and Erosion, J. Biomed. Mater. Res. Part A, 103, 2269, 10.1002/jbm.a.35357 · DOI
  118. Pack, 2013, Mathematical Modeling of Drug Delivery from Autocatalytically Degradable PLGA Microspheres—A Review, J. Control. Release, 165, 29, 10.1016/j.jconrel.2012.10.015 · DOI
  119. Zhang, Z., Zhang, B., Chen, R., Zhang, Q., and Wang, K. (2025). The Prediction of the In Vitro Release Curves for PLGA-Based Drug Delivery Systems with Neural Networks. Pharmaceutics, 17. · DOI
  120. Aghajanpour, 2025, Utilizing Machine Learning for Predicting Drug Release from Polymeric Drug Delivery Systems, Comput. Biol. Med., 188, 109756, 10.1016/j.compbiomed.2025.109756 · DOI
  121. Zhang, 2025, Core–Shell Nanoparticles with Sequential Drug Release Depleting Cholesterol for Reverse Tumor Multidrug Resistance, ACS Appl. Mater. Interfaces, 17, 6689, 10.1021/acsami.4c17858 · DOI
  122. Choi, 2025, Peptide-Harnessed Supramolecular and Hybrid Nanomaterials for Stimuli-Responsive Theranostics, Coord. Chem. Rev., 539, 216737, 10.1016/j.ccr.2025.216737 · DOI
  123. Makharadze, D., del Valle, L.J., Katsarava, R., and Puiggalí, J. (2025). The Art of PEGylation: From Simple Polymer to Sophisticated Drug Delivery System. Int. J. Mol. Sci., 26. · DOI · Paper page
  124. Sanchez, 2017, Effect of Partial PEGylation on Particle Uptake by Macrophages, Nanoscale, 9, 288, 10.1039/C6NR07353K · DOI
  125. Taghavimandi, 2025, Beyond PEGylation: Nanoparticle Surface Modulation for Enhanced Cancer Therapy, Health Nanotechnol., 1, 13, 10.1186/s44301-025-00014-4 · DOI
  126. Pedrosa, 2024, Exploring the Impact of Nanoparticle Stealth Coatings in Cancer Models: From PEGylation to Cell Membrane-Coating Nanotechnology, ACS Appl. Mater. Interfaces, 16, 2058, 10.1021/acsami.3c13948 · DOI
  127. Wang, J., Ding, Y., Chong, K., Cui, M., Cao, Z., Tang, C., Tian, Z., Hu, Y., Zhao, Y., and Jiang, S. (2024). Recent Advances in Lipid Nanoparticles and Their Safety Concerns for MRNA Delivery. Vaccines, 12. · DOI
  128. Friedl, 2021, Bioinert, Stealth or Interactive: How Surface Chemistry of Nanocarriers Determines Their Fate In Vivo, Adv. Funct. Mater., 31, 2103347, 10.1002/adfm.202103347 · DOI
  129. Bleher, 2019, Poly(Sarcosine) Surface Modification Imparts Stealth-Like Properties to Liposomes, Small, 15, 1904716, 10.1002/smll.201904716 · DOI
  130. Dasanayake, 2024, Imidazolium-Based Zwitterionic Liquid-Modified PEG–PLGA Nanoparticles as a Potential Intravenous Drug Delivery Carrier, Nanoscale, 16, 5584, 10.1039/D3NR06349F · DOI
  131. Chen, 2022, Antibody-Based Drug Delivery Systems for Cancer Therapy: Mechanisms, Challenges, and Prospects, Theranostics, 12, 3719, 10.7150/thno.72594 · DOI
  132. Mayol, B., Qubbaj, I.Z., Nava-Granados, J., Vasquez, K., Keene, S.T., and Sempionatto, J.R. (2025). Aptamer and Oligonucleotide-Based Biosensors for Health Applications. Biosensors, 15. · DOI
  133. Pisani, A., Donno, R., Gennari, A., Cibecchini, G., Catalano, F., Marotta, R., Pompa, P.P., Tirelli, N., and Bardi, G. (2020). CXCL12-PLGA/Pluronic Nanoparticle Internalization Abrogates CXCR4-Mediated Cell Migration. Nanomaterials, 10. · DOI
  134. Ribovski, 2025, Boosted Breast Cancer Treatment with Cell Membrane-Coated PLGA Nanocarriers: Investigating the Interactions with Various Cell Types, Biomater. Adv., 177, 214420, 10.1016/j.bioadv.2025.214420 · DOI
  135. Porello, 2024, Advancing Nucleic Acid Delivery through Cationic Polymer Design: Non-Cationic Building Blocks from the Toolbox, Polym. Chem., 15, 2800, 10.1039/D4PY00234B · DOI
  136. Yadav, 2024, Chitosan in Biomedicine: A Comprehensive Review of Recent Developments, Carbohydr. Polym. Technol. Appl., 8, 100551
  137. Kim, 2022, New Long-Acting Injectable Microspheres Prepared by IVL-DrugFluidicTM System: 1-Month and 3-Month in Vivo Drug Delivery of Leuprolide, Int. J. Pharm., 622, 121875, 10.1016/j.ijpharm.2022.121875 · DOI
  138. Hua, 2021, Poly(Lactic-Co-Glycolic Acid) Microsphere Production Based on Quality by Design: A Review, Drug Deliv., 28, 1342, 10.1080/10717544.2021.1943056 · DOI
  139. Schwendeman, 2014, Injectable Controlled Release Depots for Large Molecules, J. Control. Release, 190, 240, 10.1016/j.jconrel.2014.05.057 · DOI
  140. Rezvantalab, S., Drude, N.I., Moraveji, M.K., Güvener, N., Koons, E.K., Shi, Y., Lammers, T., and Kiessling, F. (2018). PLGA-Based Nanoparticles in Cancer Treatment. Front. Pharmacol., 9. · DOI
  141. Lababidi, 2025, Revamping Parkinson’s Disease Therapy Using PLGA-Based Drug Delivery Systems, npj Park. Dis., 11, 248, 10.1038/s41531-025-01081-1 · DOI
  142. Alsaab, H.O., Alharbi, F.D., Alhibs, A.S., Alanazi, N.B., Alshehri, B.Y., Saleh, M.A., Alshehri, F.S., Algarni, M.A., Almugaiteeb, T., and Uddin, M.N. (2022). PLGA-Based Nanomedicine: History of Advancement and Development in Clinical Applications of Multiple Diseases. Pharmaceutics, 14. · DOI
  143. Ramezanpour, 2022, Potential Wound Healing of PLGA Nanoparticles Containing a Novel L-Carnitine–GHK Peptide Conjugate, J. Nanomater., 2022, 6165759, 10.1155/2022/6165759 · DOI
  144. Lu, Y., Cheng, D., Niu, B., Wang, X., Wu, X., and Wang, A. (2023). Properties of Poly (Lactic-Co-Glycolic Acid) and Progress of Poly (Lactic-Co-Glycolic Acid)-Based Biodegradable Materials in Biomedical Research. Pharmaceuticals, 16. · DOI
  145. Pérez-López, A., Martín-Sabroso, C., Torres-Suárez, A.I., and Aparicio-Blanco, J. (2020). Timeline of Translational Formulation Technologies for Cancer Therapy: Successes, Failures, and Lessons Learned Therefrom. Pharmaceutics, 12. · DOI
  146. Zhang, 2020, Quality by Design Thinking in the Development of Long-Acting Injectable PLGA/PLA-Based Microspheres for Peptide and Protein Drug Delivery, Int. J. Pharm., 585, 119441, 10.1016/j.ijpharm.2020.119441 · DOI
  147. Pinto, 2019, Hot-Melt Extrusion in the Pharmaceutical Industry: Toward Filing a New Drug Application, Drug Discov. Today, 24, 1749, 10.1016/j.drudis.2019.05.013 · DOI
  148. Schoubben, 2019, Meeting the Unmet: From Traditional to Cutting-Edge Techniques for Poly Lactide and Poly Lactide-Co-Glycolide Microparticle Manufacturing, J. Pharm. Investig., 49, 381, 10.1007/s40005-019-00446-y · DOI
  149. Wan, 2016, Design of PLGA-Based Depot Delivery Systems for Biopharmaceuticals Prepared by Spray Drying, Int. J. Pharm., 498, 82, 10.1016/j.ijpharm.2015.12.025 · DOI
  150. Luan, 2006, In Situ Forming Microparticle System for Controlled Delivery of Leuprolide Acetate: Influence of the Formulation and Processing Parameters, Eur. J. Pharm. Sci., 27, 143, 10.1016/j.ejps.2005.09.002 · DOI
  151. Bi, 2025, Precise Nanoscale Fabrication Technologies, the “Last Mile” of Medicinal Development, Acta Pharm. Sin. B, 15, 2372, 10.1016/j.apsb.2025.03.040 · DOI
  152. Al Bostami, R.D., Abuwatfa, W.H., and Husseini, G.A. (2022). Recent Advances in Nanoparticle-Based Co-Delivery Systems for Cancer Therapy. Nanomaterials, 12. · DOI
  153. El-Tanani, M., Satyam, S.M., Rabbani, S.A., El-Tanani, Y., Aljabali, A.A.A., Al Faouri, I., and Rehman, A. (2025). Revolutionizing Drug Delivery: The Impact of Advanced Materials Science and Technology on Precision Medicine. Pharmaceutics, 17. · DOI
  154. Deshmukh, 2025, Next-Gen Cancer Therapy: The Convergence of Artificial Intelligence, Nanotechnology, and Digital Twin, Next Nanotechnol., 8, 100286, 10.1016/j.nxnano.2025.100286 · DOI
  155. Lawson, M., Carter, E.J., Mitchell, D.K., and Turner, J.P. (2025). Design and Evaluation of PLGA-Based Nanocarriers for Targeted and Sustained Drug Delivery in Vascular Disorders. bioRxiv. · DOI
  156. Snyder, C.S., Repetto, T., Burkhard, K.M., Tuteja, A., and Mehta, G. (2024). Co-Delivery Polymeric Poly(Lactic-Co-Glycolic Acid) (PLGA) Nanoparticles to Target Cancer Stem-Like Cells. Cancer Stem Cells, Humana. · DOI
  157. Ramalho, 2023, Transferrin-Conjugated PLGA Nanoparticles for Co-Delivery of Temozolomide and Bortezomib to Glioblastoma Cells, ACS Appl. Nano Mater., 6, 14191, 10.1021/acsanm.3c02122 · DOI
  158. Zhang, 2025, Inflammation-Modulating Polymeric Nanoparticles: Design Strategies, Mechanisms, and Therapeutic Applications, eBioMedicine, 118, 105837, 10.1016/j.ebiom.2025.105837 · DOI
  159. Xia, 2025, Biodegradable Medical Implants: Reshaping Future Medical Practice, Adv. Sci., 12, e08014, 10.1002/advs.202508014 · DOI · Paper page
  160. Sun, 2023, Smart Nanoparticles for Cancer Therapy, Signal Transduct. Target. Ther., 8, 418, 10.1038/s41392-023-01642-x · DOI · Paper page
  161. Costa, 2025, Progress on Drug Nanoparticle Manufacturing: Exploring the Adaptability of Batch Bottom-up Approaches to Continuous Manufacturing, J. Drug Deliv. Sci. Technol., 111, 107120, 10.1016/j.jddst.2025.107120 · DOI
  162. Ismail, 2021, Regulatory Considerations, Challenges and Risk-Based Approach in Nanomedicine Development, Curr. Med. Chem., 28, 7461, 10.2174/0929867328666210406115529 · DOI
  163. Wasti, S., Lee, I.H., Kim, S., Lee, J.-H., and Kim, H. (2023). Ethical and Legal Challenges in Nanomedical Innovations: A Scoping Review. Front. Genet., 14. · DOI
  164. Lin, 2025, Advances in Medical Devices Using Nanomaterials and Nanotechnology: Innovation and Regulatory Science, Bioact. Mater., 48, 353

Metadata

Authors
Stevanović, M. M., Qian, K., Huang, L., & Vukomanović, M.
Affiliations
  • Serbian Academy of Sciences and Arts (RS)
  • Shanghai Jiao Tong University (CN)
  • Jožef Stefan Institute (SI)
Corresponding author
Stevanović, Magdalena M.
ORCID
Venue
Pharmaceutics
Publisher
MDPI AG
Published
2025-12-15
Volume
17
Issue
12
Pages
1613
ISSN
1999-4923 (ISSN-L)
DOI
10.3390/pharmaceutics17121613
PMC
PMC12736669
OpenAlex
W7115169212
Cited by
42
References
0
Citations by year
2026: 42
FWCI
2.44
Type
journal article
Language
en
Open access
Licence
Locations
  • Pharmaceutics (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • Digital Archive of SASA (Serbian Academy of Sciences and Arts) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Ministry of Science, Technological Development and Innovation (MoSTDI) of the Republic of Serbia (451-03-136/2025-03/ 200175)
  • Slovenian Research Agency (J3-4531 and research program P2-0091)
Topics
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Keywords
PLGA, polymeric nanoparticles, co-delivery, gene delivery, nanocarrier design, drug release mechanism, surface functionalization, large-scale manufacturing, regulatory landscape, combination therapy, cancer therapy, nanomedicine, biodegradable polymers

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