Jump to main content
Jump to site search


Condition responsive nanoparticles for managing infection and inflammation in keratitis

Abstract

Keratitis is a major cause of avoidable visual impairment. About 30% of patients with fungal keratitis eventually become permanently blind in the developing world. Proteases, secreted by the pathogen and the host, damage the cornea before the infection is resolved. Treating keratitis is a challenge because both infection and inflammation need to be addressed. An additional challenge is maintaining a therapeutic dose at the corneal surface as blinking and tear film wash away the drugs, administered as eye drops. We have developed a nanoparticle-based drug delivery system that enhances the drug residence time by anchoring to the cornea, down-regulates inflammation and releases the antifungal drug: all in a condition-responsive manner. The expression of Toll-Like Receptors (TLR4) on the corneal epithelial cells increases in response to infection. We have conjugated anti-TLR4 antibodies on the surface of ketoconazole-encapsulated gelatin nanoparticles. Anti-TLR4 antibody not only facilitates binding of nanoparticles to the cornea, enhancing their residence time, but also reduces the levels of inflammatory cytokines. Host and fungal proteases degrade the gelatin nanoparticle, an alternate substrate for proteases, thereby reducing corneal damage and releasing the encapsulated drug, ketoconazole. After testing the efficacy of the system with human corneal epithelial cells, we have extended our studies to rat model of keratitis. The results show a significantly increased corneal retention, suppressed inflammation and resolution of infection in the infected eyes. We believe this will be an excellent approach to manage keratitis as well as other topical ocular infections.

Back to tab navigation

Supplementary files

Publication details

The article was received on 07 Feb 2017, accepted on 31 May 2017 and first published on 05 Jun 2017


Article type: Paper
DOI: 10.1039/C7NR00922D
Citation: Nanoscale, 2017, Accepted Manuscript
  •   Request permissions

    Condition responsive nanoparticles for managing infection and inflammation in keratitis

    S. Ahsan and Ch. M. Rao, Nanoscale, 2017, Accepted Manuscript , DOI: 10.1039/C7NR00922D

Search articles by author

Spotlight

Advertisements