International Journal of Pharmaceutical Investigation, 2014, 4, 4, 164-173.
Published: October 2014
Type: Original Article
Raad A. Kaskoos
Department of Pharmaceutics, College of Pharmacy, Hawler Medical University, Erbil, Iraq.a
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 moxifl oxacin (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 profi le, 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 effi ciency, 72.82 ± 3.6% and transmission electron microscopic analysis revealed a spherical shape of particles. Formulation exhibited biphasic release profi le with an initial fast release (≈25% in 1st h) followed by sustained release (≈95% in next 24 h) following Korsmeyer–Peppas model with a nonFickian diffusion process. Mox loaded CS-DS NPs exhibited a signifi cantly higher (P < 0.01), approximately 1.8-fold transcorneal permeation as well as signifi cantly higher corneal retention (P < 0.01), around 4-5-fold when compared to free solution. Developed formulation exhibited safety profi le comparable to normal saline, which was revealed by ocular tolerance test (Hen’s egg test-chorioallantoic membrane). Mox-CS-DS NPs exhibited signifi cantly 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.
Keywords:Chitosan, Dextran, Moxifloxacin, Nanoparticles, Ocular delivery, Transcorneal permeation .