Optimization of Chitosan-wrapped Linagliptin Nanosuspension for Cognitive Enhancement Through Intranasal Route

Abstract

Objective: This study aimed to design and statistically optimize the potential of intranasallydelivered chitosan-wrapped linagliptin nanosuspension as an alternative approach for brain targeting for enhancing cognitive behaviour, increasing its solubility/permeability characteristics, and reducing the side effects. Method: Linagliptin nanosuspensions were prepared by the nanoprecipitation method. We investigated the effects of independent variables, i.e., linagliptin concentration (D) and chitosan concentration (P), on the dependent factors like % drug loading (R1), % entrapment efficiency (R2), and % drug release (R3) via a central composite design. Furthermore, the optimized formulation was evaluated for surface morphology/ size, ex-vivo permeation study, in-vitro release study, and stability study. Results: The optimized formulation was further evaluated by different evaluation parameters such as FESEM and TEM study of the optimized formulation (LS 1) showed spherical morphology. Mean particle size (250.7 nm), charge (-16.3 mV), % entrapment efficiency (95.8 ± 1.45 %), and % drug loading (35.78 ± 0.19 %) were determined. Saturation solubility (0.987 mg/ml), in vitro dissolution rate (89.65 ± 0.82 %), and ex vivo permeation (82.23 ± 1.25 %) of LS 1 were higher than pure linagliptin. Conclusions: Response surface methodology was applied successfully to obtain LS 1 as an optimized formulation with enhanced solubility and dissolution characteristics at minimized dose, alleviating side effects and with improvised cognitive effects. Thus, an efficient intranasal delivery platform of linagliptin based on nanosuspension was designed for bypassing the BBB and delivering therapeutics directly to the brain. This can be a futuristic approach for enhancing cognitive effects by linagliptin nanosuspension via the intranasal route.