Innovative solid lipid nanoparticle formulations for ocular therapeutics and related patents: A systematic review
Bakr Ahmed, Nitika Saini, Veluchamy A. Barathi, Vandana Patravale, Rohan Shah, Indu Pal Kaur
Abstract
TOPIC: This systematic review explores solid lipid nanoparticles (SLNs) as innovative drug delivery systems for ocular applications. It evaluates their ability to improve bioavailability, sustain drug release, and overcome ocular barriers in treating anterior and posterior segment disorders such as dry eye syndrome, glaucoma, infections, and retinal diseases. Comparisons with traditional delivery systems and other nanoparticle platforms are also addressed. CLINICAL RELEVANCE: Ocular diseases often face challenges in effective drug delivery due to the eye's unique anatomy and physiological barriers. Current treatments, including eye drops and intravitreal injections, are limited by rapid clearance, invasiveness, and systemic side effects. SLNs offer a next-generation alternative, addressing these limitations with enhanced corneal permeability, drug retention, and targeted delivery. METHODS: A comprehensive search was conducted across PubMed, Scopus, Web of Science, and Google Scholar, focusing on studies and patents published from 2010 to 2024. Inclusion criteria targeted original studies using SLNs for ocular applications, excluding studies describing only liposomes and micelles. The PRISMA 2020 guidelines were followed, and data extraction included active pharmaceutical ingredients (APIs), particle size, zeta potential, and therapeutic outcomes. Risk of bias was evaluated using appropriate frameworks. RESULTS: Twenty-eight (28) studies and twenty (20) patents met inclusion criteria, covering SLNs encapsulating APIs such as econazole, atorvastatin, and cannabinoids. Key findings highlighted enhanced bioavailability (up to 12-fold in vitreous humour for atorvastatin-SLNs), sustained release (24-96 h), and improved corneal permeability (up to 287 % higher than controls). Patented formulations incorporated cationic SLNs, PEGylated lipid nanoparticles, and bioactive-loaded SLNs, demonstrating superior stability and therapeutic efficacy. No significant ocular toxicity was observed across in vitro and in vivo studies. CONCLUSION: SLNs represent a transformative approach for ocular drug delivery, combining safety, scalability, commercial viability, and enhanced therapeutic outcomes due to higher permeability and controlled release. However, challenges remain in industrial translation and regulatory approvals. Future research should focus on quality by design (QbD) formulation development; simple, viable, energy-efficient, and preferably organic solvent-free methods of preparation; and leveraging advanced characterization techniques like SAXS and molecular simulations to refine and define SLNs design, molecular structure, and function.