Solid Lipid Nanoparticles for Ocular Delivery of Isoniazid: Evaluation, Proof of Concept and In Vivo Safety & Kinetics

Abstract

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::

• cellular uptake
• corneal permeability
• cytotoxicity
• in vitro release
• in vivo ocular toxicity
• minimum inhibitory concentration
• microemulsification
• ocular tissue uptake
• ocular tuberculosis
• stability studies

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/full/10.2217/nnm-2018-0278

Financial & competing interests disclosure

This project was supported by grants from the Department of Biotechnology (DBT), New Delhi, India. The authors are thankful for funding provided by DBT India. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Acknowledgments

The authors acknowledge the SAIF facility of DST at Panjab University, Chandigarh, India and PURSE, DST-FIST and UGC-CAS funded facility of UIPS used for characterization of INH-SLNs. The authors also acknowledge Sabyasachi Rakshit from IISER, Mohali, India, for providing facility for atomic force microscopy.

Additional information

Funding

This project was supported by grants from the Department of Biotechnology (DBT), New Delhi, India. The authors are thankful for funding provided by DBT India. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.