Tabriz University of Medical Sciences Advanced Pharmaceutical Bulletin 2228-5881 16 3 2026 09 30 PLGA Based "Lipid-Polymer Hybrid Nanoparticles": A Convergent Platform of Active and Targeted Drug Delivery 463 481 10.34172/apb.46136 EN Rajlaxmi Patro https://orcid.org/0009-0009-9243-4669 Ch. Niranjan Patra https://orcid.org/0000-0002-5022-8746 Subrata Mallick https://orcid.org/0000-0002-6606-1223 REVIEW 10.34172/apb.46136 2025 08 05 2026 03 20 A promising class of nano-carriers known as "Lipid-Polymer Hybrid Nanoparticles" (LPHNPs) combines the biocompatibility and functionality of lipid-based systems with the structural advantages of polymeric nanoparticles. This review summarizes structural classifications and preparation methods of PLGA-based lipid–polymer hybrid nanoparticles (LPHNPs). An exhaustive elaboration of various preparation techniques is provided, with an emphasis on their scalability and influence on physicochemical properties. Methods include solvent evaporation, nanoprecipitation, emulsion solvent evaporation, and homogenization, among others. To define the size of particles, morphology, surface charge, and thermal behavior, important characterization techniques such as differential-scanning-calorimetry, transmission electron microscopy (TEM), zeta potential (ZP), and particle size (PS) are described. Recent developments and therapeutic results are discussed here, followed by an extensive range of biomedical applications, spanning from drug delivery, gene therapy, and vaccine development to diagnostic imaging. In conclusion, the review highlights current challenges related to stability, repeatability, and targeted distribution. It also elaborates on potential future developments of personalized medicine, stimuli-responsive systems, and regulatory considerations. LPHNPs have the potential to serve as flexible platforms for the next generation of therapeutic and diagnostic modalities, potentially revolutionizing the field of nanomedicine.