Design and assessment of in-situ nasal gel incorporated with nanostructured cubosomes for the targeted therapy of schizophrenia

This study aimed to pioneer an innovative treatment tactic for schizophrenia by harnessing the potential of haloperidol (HPD) loaded nanostructured cubosomes infused into an in-situ nasal gel. An Artocarpus heterophyllus L. (Jackfruit) mucilage (AH mucilage) was used as a novel mucoadhesive substance in intranasal formulation. The formulation strategy included high-pressure homogenization (HPH) employing poloxamer 407 functions as a surface-active agent, serving the role of a surfactant, while polyvinyl alcohol is employed as a stabilizing agent in the formulation. The resulting HPD cubosomal structure exhibited particle size ranging from 64 to 198 nm, facilitating efficient brain delivery through the nasal route. Among the prepared batches, H7 stood out notably with a particle size (PS) of 156 ± 7.46 nm, the polydispersity index (PDI) was determined to be 0.2667, indicating the degree of heterogeneity in the particle size distribution. Simultaneously, the zeta potential (ZP) was measured at -21.71 mV, signifying the electrostatic charge on the particles in the solution. Entrapment efficiency of 78.80 ± 0.76% and drug content of 84 ± 1.00% were achieved. Transmission electron micrographs vividly illustrated the cubosomal morphology. In ex-vivo investigations conducted on sheep nasal mucosa, the cubogel formulated with AH mucilage displayed superior nasal mucoadhesion and enhanced drug permeation in comparison to Carbopol P934, a synthetic mucoadhesive agent. In conclusion, the developed HPD cubogel, incorporating mucoadhesive mucilage from Artocarphus heterophyllus L., presents a hopeful and inventive strategy for the effective management of schizophrenia.