Title : Brain targeted nanotherapeutics: An enticing journey from ideation to product realization Vandana B Patravale
Abstract:
Dementia (neurodegenerative ailments) accounts for over 50 million cases worldwide with estimated new 7.7 million cases every year. Neurodegenerative ailments associated progressive decline in clinical condition mainly results from poor transport of therapeutic actives across blood brain barrier (BBB) and oxidative stress induced disease progression. To overcome this challenge, we developed smart targeted micellar nanocarriers (t-micelles) comprising a novel lipid bioconjugate (t-ligand) with an inherent ability to circumvent BBB via active transport pathway (patented technology). The t-ligand was designed using in silico glide molecular docking on BBB active transport receptor crystal structure. Designed t-ligand exhibited selective affinity binding at the BBB active transport receptor site and was synthesized successfully. The t-ligand exhibited self-assembling property and the resulting micellar geometry was optimized using SANS tool.
For therapeutic application, t-micelles of donepezil (first line drug for treatment of dementia) were developed and incorporated in gel for microneedle assisted transdermal delivery. t-Micelles showed 1.6 fold higher brain permeation in zebra fish model as competed to plain micelles. The Draize patch test confirmed suitability of proposed treatment regimen and showed 4 fold increment in skin permeability flux as compared to treatment without microneedle patch. In vivo pharmacokinetic and biodistribution studies demonstrated 3 fold rise in bioavailability with significantly high donepezil brain uptake when given as microneedle pretreated transdermal t-micellar gel in contrast to marketed oral formulation. As second application, t-micelles of curcumin (antioxidant-neuroprotective drug for treatment of neurodegenerative disorders) were also developed and incorporated into a nasal spray for nose-to-brain delivery. In vivo pharmacokinetic and biodistribution studies demonstrated enhanced brain transport of curcumin with t-micelles mainly in the dementia sensitive areas of brain viz. olfactory region, hippocampus and cerebellum. The studies confirmed the potential of t-micelles as a platform Trojan Horse strategy to improve the brain delivery of therapeutic actives and confirmed its suitability towards effective delivery via multiple routes of administration.
Audience take away:
• A scientific and rationale thought process for innovative targeted nanoformulation development
• Step by step approach towards in-depth planning and execution from ideation to product realization
Key features:
• Next generation novel, targeted and efficacious strategy to treat neurological ailments
• Industrially feasible and scalable platform technology
• Patented technology
