Aim: Evaluation of solid lipid nanoparticles (SLNs) for ocular delivery of isoniazid (INH).
Materials & methods: INH-SLNs were characterized for morphological, thermal, crystalline and nuclear magnetic resonance properties. In vitro release and ex vivo corneal permeability of INH-SLNs was also evaluated. Proof-of-concept uptake studies were performed in corneal and conjunctival cell lines and in vivo in rat eye using fluorescein-labeled SLNs. Antimycobacterial activity of INH-SLNs was confirmed. In vivo aqueous humor pharmacokinetics, toxicity and tolerance was performed in rabbit/rat eye.
Results: INH-SLNs showed extended release (48 h), enhanced corneal permeability (1.6-times), five-times lower MIC, significant in vitro and in vivo uptake of fluorescein-labeled SLNs, 4.2-times ocular bioavailability (area under the curve) and in vivo acute and repeat dose safety.
Conclusion: INH-SLNs are an effective ocular delivery system.
Keywords: ocular toxicity; release; cellular uptake; corneal permeability; cytotoxicity; microemulsification; minimum inhibitory concentration; ocular tissue uptake; ocular tuberculosis; stability studies.