Engineering Lipid Nanoparticles for Enhanced Drug Encapsulation and Release: Current Status and Future Prospective

Lipid nanoparticles have emerged as a versatile and effective platform for drug delivery, offering significant advantages such as biocompatibility, scalability, and the ability to encapsulate diverse therapeutic agents including nucleic acids, proteins, and small-molecule drugs. This review comprehensively explores engineering strategies for enhancing drug encapsulation efficiency and achieving controlled release within LNPs. Key formulation components such as ionizable and PEGylated lipids, along with lipid matrix design, play pivotal roles in optimizing nanoparticle stability, payload capacity, and release kinetics. Advances in fabrication methods including microfluidics and solvent mixing techniques have enabled reproducible production of high-quality LNPs tailored for specific therapeutic applications. The critical role of engineered LNPs is exemplified by their success in RNA therapeutics, notably COVID-19 mRNA vaccines, and expanding applications in cancer therapy and protein delivery. The review also highlights challenges like balancing stability and drug loading, minimizing toxicity, and scaling up manufacturing, alongside emerging solutions. Future perspectives emphasize the development of novel lipid materials, hybrid nanocarriers, and integration with personalized medicine and gene editing. These advances position LNPs as a cornerstone for next-generation nanomedicine platforms aimed at safe, efficient, and targeted delivery for a broad spectrum of diseases. The aim of this review is to comprehensively examine the engineering principles and formulation strategies employed to enhance drug encapsulation efficiency and achieve controlled release in lipid nanoparticles.