Development and Assessment of a Candesartan-loaded Bilosomal In Situ gel for targeted Nose-to-Brain Delivery

ABSTRACT

INTRODUCTION:

Candesartan is an angiotensin II receptor blocker that has been used in the treatment of arterial hypertension. Its repurposing in migraine treatment, due to potential mechanisms involved in migraine pathophysiology, is currently being explored. Repurposing medications lowers their development costs and time to market, and the greatest benefit of repurposing is that it offers tailored therapy at a lower cost. Candesartan is a BCS class II drug with low solubility and high permeability. The oral bioavailability of Candesartan is very low, approximately 15%. Therefore, it is important to find an alternate route to deliver Candesartan to increase its bioavailability. In this study, we assess the potential of delivering Candesartan intranasally, directly to the brain, through the preparation of bilosomes incorporated into a muco-adhesive in situ gel to increase its retention time and for brain targeting to treat migraines.

METHODS:

Candesartan bilosomes will be prepared by using a thin-film hydration technique. This formulation will be characterized in terms of vesicle size, entrapment efficiency, zeta potential, morphology, and Fourier transform infrared spectroscopy. Candesartan bilosomes will be incorporated into an in situ gel and will be evaluated in terms of pH, viscosity, muco-adhesive strength, spreadability, gel strength, in vitro release, ex vivo permeation, and in vivo study.

CONCLUSION:

A bilosomal system that effectively encapsulates Candesartan will enhance its solubility, stability, and permeation across the nasal mucosa. In situ gels exhibit favorable muco-adhesive properties which contribute to prolonged contact time with the nasal mucosa, accelerating sustained drug release and enhancing brain-targeted delivery. A Candesartan-loaded bilosomal in situ gel may provide a non-invasive and efficient alternative for migraine management.