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

Nanomedicine (Lond). 2019 Feb;14(4):465-491. doi: 10.2217/nnm-2018-0278. Epub 2019 Jan 29.

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: ocular toxicity; release; cellular uptake; corneal permeability; cytotoxicity; microemulsification; minimum inhibitory concentration; ocular tissue uptake; ocular tuberculosis; stability studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cornea / metabolism
  • Drug Carriers / chemistry
  • Drug Delivery Systems / methods
  • Eye / metabolism*
  • Isoniazid / chemistry*
  • Isoniazid / pharmacokinetics*
  • Magnetic Resonance Spectroscopy
  • Microscopy, Atomic Force
  • Microscopy, Electron, Transmission
  • Rabbits
  • Rats
  • Spectroscopy, Fourier Transform Infrared
  • Swine
  • X-Ray Diffraction

Substances

  • Drug Carriers
  • Isoniazid