Thermosensitive in-situ gel of Nifedipine: A strategy to offset cognition impairment in Alzheimer's disease

Increased intracellular Ca2+ accumulation plays a pivotal role in the development and progression of Alzheimer's disease (AD). Thus, utilization of calcium channel blockers presents an elite option to combat AD-associated cognition impairment. The present work investigated the neuroprotective potential of nifedipine, a L-type calcium channel blocker (LTCC) by preparing a nanostructured lipid carrier-based intranasal in-situ gelling system (NF-NLC gel). The prepared NF-NLCs were optimized using 32 Full factorial design wherein the ratio of solid: liquid lipid was considered as an independent variable. The prepared NF-NLCs had optimal particle size of ∼94.86±14.04 nm, with PDI of ∼0.189±0.02, ZP of ∼−12.1 ± 10.05 mV, and % entrapment efficiency of ∼90.5±15.21%. Transmission electron microscopy displayed spherical morphology of NF-NLCs. Further, NF-NLCs were loaded into a thermosensitive gel matrix comprised of HPMC K4M (0.3%) and Poloxamer 407 (15%). The prepared NF-NLC gel exhibited optimal gelation time, temperature, and pseudo-thixotropic behavior. Moreover, the gelling system showed sustained release (∼24h) and enhanced permeation across the nasal mucosa. The in-vivo studies in the AlCl3 induced AD model revealed substantial improvement in cognitive ability along with reduced oxidative damage. Overall, the developed NF-NLC gel presents a viable strategy to combat cognition impairment in AD. [Display omitted]