Cubic liquid crystalline nanoparticles: optimization and evaluation for ocular delivery of tropicamide

Abstract

The purpose of this study was to investigate the potential of cubic liquid crystalline nanoparticles for ocular delivery of tropicamide. Ultrasound-assisted fragmentation of cubic liquid crystalline bulk phases resulted in cubic liquid crystalline nanoparticles employing Pluronic F127 as dispersant. The effects of process variables such as sonication time, sonication amplitude, sonication depth, and pre-mixing time on particle size and polydispersity index was investigated using central composite design. The morphology of tropicamide-loaded nanoparticles was found to be nearly cubical in shape by transmission electron microscopy observation. Further, small angle X-ray scattering experiment confirmed the presence of D and P phase cubic structures in coexistence. The optimized tropicamide-loaded cubic nanoparticles showed in vitro corneal permeation of tropicamide across isolated porcine cornea comparable to its commercial preparation, Tropicacyl®. Ocular tolerance was evaluated by Hen’s egg–chorioallantoic membrane test and histological studies. The results of in vivo mydriatic response study demonstrated a remarkably higher area under mydriatic response curve (AUC_{0→1440 min}) values of cubic nanoparticles over Tropicacyl® indicating better therapeutic value of cubic nanoparticles. Furthermore, tropicamide-loaded cubic nanoparticles exhibited prolonged mydriatic effect on rabbits as compared to commercial conventional aqueous ophthalmic solution.

Keywords:

• Central composite design
• cubic nanoparticles
• ocular delivery
• tropicamide
• ultrasound

Acknowledgements

The authors express gratitude to SAIF, AIIMS, New Delhi and SMITA Research labs, IIT, Delhi for TEM and SAXS analysis. The authors are extremely grateful to the Coordinator, DST FIST, Dept. of Pharmaceutical Sciences (GJUS&T, Hisar) for particle size analysis.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.