Nanotransfersomes of carvedilol for intranasal delivery: formulation, characterization and in vivo evaluation

Abstract

Context: Development of carvedilol-loaded transfersomes for intranasal administration to overcome poor nasal permeability and hepatic first pass effect so as to enhance its bioavailability.

Objective: The purpose of this study was to develop carvedilol-loaded transfersomes containing different edge activators (EAs) then evaluating the in vivo behavior of the optimized formula in rabbits.

Methods: The vesicles were prepared by incorporating different EAs including Span 20, Span 60, Tween 20, Tween 80, and sodium deoxycholate (SDC) in the lipid bilayer and each EA was used in three different ratios with respect to phosphatidylcholine (PC) including 95:5%, 85:15%, and 75:25% w/w (PC:EA). Evaluation of transfersomes was carried out in terms of shape, size, entrapment efficiency (EE), in vitro release, ex vivo permeation, confocal laser scanning microscopy (CLSM), and stability studies. The pharmacokinetic study of the optimized formula was conducted in rabbits.

Results: The mean diameter of the vesicles was in the range of 295–443 nm. Transfersomes prepared with 95:5% (w/w) (PC:EA) ratio showed highest EE% where Span 60 gave the highest values. Whereas those prepared using 85:15% w/w ratio showed highest percentages of drug release where SDC was superior to other EAs. The developed transfersomes exhibited significantly higher amounts of carvedilol permeated through nasal mucosa. CLSM of formula T14 containing SDC with 85:15% (w/w) (PC:EA) ratio revealed high permeation across the nasal mucosa.

Conclusion: The nanotransfersomal vesicles were significantly more efficient in nasal delivery of carvedilol with absolute bioavailability of 63.4%.

Keywords:

• Carvedilol
• edge activators
• intranasal
• nanotransfersomes
• pharmacokinetic study

Acknowledgements

The authors would like to thank Prof. Dr. Mahmoud Al-Begawy and Dr. El-Shaymaa Al-Nahass, Department of Pathology, Faculty of Veterinary Medicine, Beni Suef University for helping in histopathological studies and CLSM studies. We also are grateful to Dr. Reda Abd Allah, Department of Anatomy and Embryology, Faculty of Veterinary Medicine, Beni Suef University for helping in trimming nasal mucosa for ex vivo permeability studies and Dr. Ossama M. Sayed, Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni Suef University for helping in analysis of plasma samples.

Declaration of interest

The authors report that they have no conflicts of interests.