Lipid carrier-based intranasal delivery of calcium channel blockers for Alzheimer's disease.

Abstract

Background: Felodipine (FLD) is an L-type calcium channel blocker with pronounced neuroprotection against Alzheimer's disease (AD). Unfortunately, the efficacy of FLD has been impeded by limited solubility, poor bioavailability, and sub-optimal accumulation. Thus, the current study unfolds the potential of nanostructured lipid carriers based on in-situ gel of FLD (FLD-NLCs gel) to ameliorate dementia.

Methods: The FLD-contained NLCs were prepared using the microemulsion-sonication method and further integrated into thermosensitive gel comprised poloxamer 407 and HPMC K4M. The formulation was evaluated by ex-vivo permeation study, cell culture studies, and in-vivo efficacy study. The toxicity of formulation was assessed by HET-CAM assay, and nasal cilitoxicity study.

Results: The optimized FLD-NLCs had nanoscaled dimension, spherical shape, and augmented %EE (~96%). The FLD-NLCs gel displayed biphasic release, with ~1.3-fold higher permeation as relative to free FLD. The HET-CAM assay and cell culture study revealed compatible nature of formulation. The in-vivo biochemical, neurotransmitter, and inflammatory marker determination revealed neuroprotective and restorative potential of the FLD-NLCs gel.

Conclusions: The repurposing tactic of FLD presents a viable concept to combat AD. Also, the NLC-based temperature responsive intranasal gel exemplifies a practical approach to augment the efficacy of FLD.