Chitosan nanoparticles amplify the ocular hypotensive effect of cateolol in rabbits

Purpose: To assess the potential of chitosan (CS) nanoparticles for ocular drug delivery by investigating their intraocular retention by gamma-scintigraphy and intraocular pressure reduction. Methods: Carteolol (CRT) loaded CS-NPs were prepared by ionotropic gelation method. A four-factor three-level Box-Behnken design was employed to investigate the influence of independent variables on particle size, loading capacity and entrapment efficiency. Characterization was done for particle size, encapsulation efficiency, loading capacity and in vitro drug release and transcorneal permeation, histopathology and confocal microscopy, in vitro ocular tolerance. Intraocular retention was assessed by gamma-scintigraphy, and intraocular pressure was measured by tonometer betamethasone induced glaucoma rabbits. Results and discussion: The optimized nanoparticles showed a particle size of 243 nm (PDI - 0.304 +/- 0.04) and drug loading 49.21 +/- 2.73% with entrapment efficiency of 69.57 +/- 3.54%. In vitro release studies showed a sustained release for 24 h as compared to drug solution. Ex vivo studies showed good permeation with non-significant changes in cornea anatomy indicating its safe nature. gamma-Scintigraphy study showed good spread and retention (<0.05) in precorneal area as compared to the aqueous CRT solution and prolonged reduction in intraocular pressure (P<0.001). Conclusion: These results indicate that CS nanoparticles are promising vehicles of CRT for ocular drug delivery. (C) 2014 Elsevier B.V. All rights reserved.