Intranasal delivery of chitosan decorated nanostructured lipid carriers of Buspirone for brain targeting: Formulation development, optimization and In-Vivo preclinical evaluation

The current research was portrayed to design and optimize the Chitosan (CH) coated Buspirone-loaded nanostructured lipid carriers (BPE-CH-NLCs) for nose to brain delivery. NLCs were developed by solvent diffusion evaporation technique, coated with CH, and then optimized to the maximum efficiency using the quality by design (QbD) based Box-Behnken design (BBD). Glyceryl monostearate (GMS) & oleic acid mixture and tween 80 were used as a lipid and surfactant, respectively. The prepared NLCs were subjected to in-vitro characterization. In-vivo pharmacokinetic and neuro-pharmacokinetic (drug targeting efficiency-DTE, direct transport percentage-DTP) parameters were evaluated on Wister rats. The results revealed that the optimized formulation exhibited acceptable PS (190.98 ± 4.72 nm), ZP (+17.47 mV), and EE (80.53 ± 1.26% w/w), and the TEM image showed that the drug was incorporated adequately in NLCs. DSC findings exposed that the drug was present in amorphous form within the NLCs. The optimized formulation exhibited 27.61 months shelf life and was found to be stable under studied conditions. The value of AUC (bioavailability) for BPE-CH-NLCs administered i.n was found to be 3.06 folds compared to BPE-CH-NLCs administered i.v, and 2.17 folds compared to BPE-Sol administered i.n. A higher value of DTE (1462.49%) for developed NLCs confirmed the brain targeting efficiency of these lipid nanoparticles. DTP value for BPE-CH-NLCs (93.16%) was significantly (p < 0.05) higher than BPE-Sol (81.63%), indicating the efficient targeting potential of lipid nanoparticles compared to drug solutions. Finally, it could be possible to infer that GMS-Oleic acid-based NLCs coated with CH might be effective carriers to administer BPE to the brain via the nasal route.