Solid lipid nanoparticles for ocular delivery of isoniazid: evaluation, proof of concept and in vivo safety & kinetics

• Published in: Nanomedicine (London, England) Vol. 14; no. 4; pp. 465 - 491
• Main Authors: Singh, Mandeep, Guzman-Aranguez, Ana, Hussain, Afzal, Srinivas, Cheerneni S, Kaur, Indu P
• Format: Journal Article
• Language: English
• Published: England Future Medicine Ltd 01.02.2019
• Subjects: Bioavailability; Cornea; Design of experiments; Drug delivery systems; Drug dosages; Fourier transforms; Lipids; Microemulsions; Microscopy; Nanoparticles; Neurotoxicity; NMR; Nuclear magnetic resonance; Particle size; Permeability; Phase transitions; Physiology; Spectrum analysis; Surfactants; Tuberculosis; United States > US; ocular tissue uptake; ocular tuberculosis; stability studies; corneal permeability; ocular toxicity; release; microemulsification; cytotoxicity; cellular uptake; minimum inhibitory concentration
• ISSN: 1743-5889; 1748-6963
• DOI: 10.2217/nnm-2018-0278

Evaluation of solid lipid nanoparticles (SLNs) for ocular delivery of isoniazid (INH). 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. 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. INH-SLNs are an effective ocular delivery system.