Formulation development of functionalized brain targeted drug delivery system for the management of cognitive impairment

Abstract

Background: Dementia has become one of the prime reason for the partial or complete incapacity of the geriatric population leading to a burden on family members. The challenge for neurotherapeutics is to permeate the unique biological barrier intended to protect the brain by restricting the entry of exogenous molecules inside the brain. To overcome these challenge, it was hypothesized to conjugate the nps with identified endogenous ligand i.e. glutathione and LC which are routinely internalize via NMDA, AMPA and PepT1, PHT2 receptors mediated transport system respectively. newlineAim and objective: Aim was to fabricate the peptide-linked polymeric nanoconstructs of asiatic acid and donepezil via receptor-mediated brain delivery for the management of cognitive impairment. So the objective of the study was to optimize the nps as per the desired target product profile (TPP) in order to improve the brain bioavailability followed by in-vivo evaluation. newlineMaterials and Methods: In the present study, 6-coumarin was selected as an inactive model drug for the development of proof-of-concept for evaluating brain targeting efficiency of the conjugated peptide. Asiatic acid was identified as a model drug because of least explored previously as neurotherapeutic and its clinical application is hampered due to poor bioavailability. Donepezil was USFDA approved as acetylcholinesterase inhibitor but least explored for their influence on amyloid-beta aggregation, tau phosphorylation, and GSK3and#946; hence, selected as a second model drug. Additionally, there is a need to develop a modified dosage form of donepezil in order to prevent gastrointestinal side effect and required frequent dosing. Bovine serum albumin and poly (lactic-co-glycolic acid) (50: 50) were selected as a polymeric carrier newline