Nanostructured cubosomes in an in situ nasal gel system: an alternative approach for the controlled delivery of donepezil HCl to brain

Abstract

The purpose of this research was to develop cubosomal mucoadhesive in situ nasal gel to enhance the donepezil HCl delivery to the brain. Glycerol mono-oleate (GMO) and surfactant poloxamer 407 were used to prepare cubosomes. The developed formulations were characterized for particle size (PS), poly dispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE), transmission electron microscopy (TEM), in vitro drug release and in vivo bio-distribution study in blood and brain tissue. Central composite design was used for the optimization purpose and the selected formulation (containing GMO 2 g and poloxamer 1.5%) was prepared in presence of gellan gum and konjac gum as gelling agent and mucoadhesive agent respectively. The optimal cubosomal dispersion and optimal cubosomal mucoadhesive in situ nasal gel were subjected to in vivo bio-distribution studies in rat model. It showed significantly higher transnasal permeation and better distribution to the brain, when compared to the drug solution. Thus, the formulated cubosomal mucoadhesive in situ gel could be considered as a promising carrier for brain targeting of CNS acting drugs through the transnasal route.

Keywords:

• Donepezil HCl
• intranasal delivery
• cubosomes
• mucoadhesion
• in situ gel
• bio-distribution
• brain targeting

Acknowledgement

Authors are thankful to Dr. Reddy’s Lab, Hyderabad, India, and Mohini Organics Pvt. Limited, Mumbai, India, BASF Limited, Mumbai, India, Gangwal Chemicals Pvt. Ltd, Mumbai, India for providing gift samples of donepezil HCl, glycerol monooleate, Poloxamer 407 and Konjac Glucomannan respectively. Authors are also thankful to Mrs. Babita Agarwal and Mrs. Sampada Dalvi for their help in plasma analysis using HPLC. Thanks are also due to Principal Dr. K. R. Khandelwal, JSPM’s Rajarshi Shahu College of Pharmacy & Research, Pune and Principal Dr. M. J. Patil, Marathwada Mitra Mandal’s College of Pharmacy, Pune, for providing required infrastructure to carry out this study. We also extend our sincere thanks to Dr. Vaishali Mute of JSPM’S Rajarshi Shahu College of Pharmacy & Research for her help in carrying out preclinical study.

Disclosure statement

No potential conflict of interest was reported by the authors.