Characterization of withanolides and bacoside A-loaded proniosomes: effect on oxidative stress and survival under hypergravity in rodent model

Abstract

Objective

This work provides characterization of withanolides and bacoside A proniosomes, and evaluating their potency in rat model for combating oxidative stress-induced blood–brain barrier (BBB) damage and their survival under hypergravity.

Significance

The delivery system was aimed for sustained drug release in plasma and brain, which could improve their efficiency and provide a therapeutic approach to combat oxidative damage and restore BBB integrity.

Methods

Proniosomes were prepared using withanolides extracted from the roots of W. somnifera and bacoside A derived from the leaf extract of B. monnieri by thin film hydration technique. In vitro release of withanolides and bacoside A from the proniosomes was studied. In vivo experiments were conducted in Wistar Albino rat model to evaluate the efficacy of drug-loaded proniosomes in improving the antioxidant activity in plasma and brain, restoring BBB integrity and combating hypergravity conditions.

Results

The withanolides and bacoside A-loaded proniosomes showed slow and sustained release of just 62.0 ± 2.87 and 62.9 ± 3.41%, respectively, in 9 h period against the release of 98–99% for the extracts that served as control. Trials conducted in vivo revealed a significant (p < .05) increase in the activity of antioxidant enzymes in both plasma and brain. Also, minimal extravasation of Evans blue dye into the brain (15 ± 0.03 and 16 ± 0.03 ng/g in treated groups against 110 ± 0.01 ng/g in control) of the rats fed with drug-loaded proniosomes was indicative of minimal damage to BBB. Rats fed with drug-loaded proniosomes survived to the extent of 75–83.3% against simulated hypergravity as compared to the control group in which only 50% survived.

Conclusion

Proniosomes provided sustained release of drugs, which helped to protect BBB integrity, thereby combating hypergravity.

Graphical abstract

Keywords:

• Bacoside A
• BBB integrity
• hypergravity
• lipid peroxidation
• proniosomes
• withanolides

Acknowledgements

The authors acknowledge Director, ICAR-NIANP, Bengaluru, India for permission to conduct this research. The first author also acknowledges the Indian Council of Medical Research, New Delhi, India for supporting the project, and the Jain University for permission to carry out the work at ICAR-NIANP. The authors are grateful to Dr. D. Roy Mahapatra of Indian Institute of Science, Bengaluru for designing the animal centrifuge for hypergravity tests. Similarly, the facility provided for in vitro release studies by Dr. Asha A.N. of Al-Ameen College of Pharmacy, Bengaluru is sincerely acknowledged.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The first author also acknowledges the Indian Council of Medical Research, New Delhi, India for supporting the project.