Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICAL INVESTIGATION
Volume 4, Issue 4, Pages 164-173Publisher
MEDKNOW PUBLICATIONS & MEDIA PVT LTD
DOI: 10.4103/2230-973X.143114
Keywords
Chitosan; dextran; moxifloxacin; nanoparticles; ocular delivery; transcorneal permeation
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Introduction: Management of ocular surface disease by conventional formulation is limited by poor residence of drug at cul-de-sac of eye. To overcome this limitation, prolonged released mucoadhesive chitosan (CS)-dextran sulfate (DS) nanoparticles (NPs) were investigated for the prolonged topical ophthalmic delivery of moxifloxacin (Mox). Methods: Formulation was optimized by 3-factors (CS, DS, and Mox concentration), 3-levels (1, 0, 1) Box-Behnken design. Optimized formulation was characterized for various in-vitro attributes, including particles size, zeta potential, shape and morphology, in-vitro release profile, corneal permeation, corneal retention, ocular tolerance test as well as antimicrobial activity. Results: Average hydrodynamic particle size of statistically optimized formulation was found to be 279.18 +/- 15.63 nm with good polydispersity index, 0.367 +/- 0.016 and positive zeta potential, 31.23 +/- 1.32. NPs showed entrapment efficiency, 72.82 3.6% and transmission electron microscopic analysis revealed a spherical shape of particles. Formulation exhibited biphasic release profile with an initial fast release (approximate to 25% in 1st h) followed by sustained release (approximate to 95% in next 24 h) following Korsmeyer-Peppas model with a nonFickian diffusion process. Mox loaded CS-DS NPs exhibited a significantly higher (P < 0.01), approximately 1.8-fold transcorneal permeation as well as significantly higher corneal retention (P < 0.01), around 4-5-fold when compared to free solution. Developed formulation exhibited safety profile comparable to normal saline, which was revealed by ocular tolerance test (Hens egg test-chorioallantoic membrane). Mox-CS-DS NPs exhibited significantly high (P < 0.01) antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa. Conclusion: In-vitro and ex-vivo studies revealed that developed formulation could be a potential substitute for prolonged topical ocular delivery.
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