A method for enhancing the ocular penetration of eye drops using nanoparticles of hydrolyzable dye

Koichi Baba, Yuji Tanaka, Akira Kubota, Hitoshi Kasai, Shunji Yokokura, Hachiro Nakanishi, Kohji Nishida

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

This report describes a method for enhancing the ocular penetration of eye drops using nanoparticles of hydrolyzable dye, which is similar to a prodrug approach. The entry of eye drops into the ocular globe is restricted predominantly by corneal barrier functions. The barrier functions are epithelial tight junctions as well as a physicochemical property consisting of the opposite characteristics of a lipophilic epithelium and a hydrophilic stroma. We found that using a formulation of nanoparticles of hydrolyzable dye (with particles of 200 nm in diameter on average) attained a greater than tenfold higher (about 50-fold) ocular penetration than that of micron-sized particles. The nanoparticles were prepared by a carrier-free technique; i.e., the reprecipitation method. Confocal laser fluorescence microscopy showed that dyes originating from the nanoparticles surmounted the corneal epithelium barrier, which has tight junctions, and achieved deeper penetration into the cornea. The high penetration rate of the dyes into the cornea was attributed to the size of particles (i.e., nanoparticles) and a transformation of dye polarity from lipophilic to hydrophilic in in vivo hydrolysis reactions. We concluded that utilizing in vivo hydrolysis reactions to alter the physicochemical nature of nanoparticles consisting of hydrolyzable compounds was an effective approach for enhancing the ocular penetration of eye drops.

Original languageEnglish
Pages (from-to)278-287
Number of pages10
JournalJournal of Controlled Release
Volume153
Issue number3
DOIs
Publication statusPublished - 2011 Aug 10

Keywords

  • Confocal laser fluorescence microscopy
  • Eye drops
  • Hydrolysis
  • Nanoparticles
  • Ocular penetration

ASJC Scopus subject areas

  • Pharmaceutical Science

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