Ion-activated In Situ Gel of Gellan Gum Containing Chrysin for Nasal Administration in Parkinson’s Disease

Introduction: This study focused on creating an innovative treatment approach for Parkinson's disease (PD), a progressive neurodegenerative condition characterized by the loss of specific neurons in the brain. Aim: The research aimed to develop a nasal gel using gellan gum containing a complex of chrysin with hydroxypropyl-β-cyclodextrin (HP-β-CD) to enhance the drug’s solubility and stability. Method: The formulation process involved utilizing central composite design (CCD) to optimize the concentrations of gellan gum and HPMC E5, with viscosity and mucoadhesive strength as key factors. The resulting optimized In Situ gel comprised 0.7% w/v gellan gum and 0.6% w/v HPMC E5, exhibiting desirable viscosity levels for both sol and gel states, along with robust mucoadhesive properties. The formulated gel underwent comprehensive evaluation, including assessments for gelation, drug content, in vitro drug release, ex vivo permeation, and histopathology. Result: The findings demonstrated superior drug release from the In Situ gel compared to standalone chrysin. Ex vivo studies revealed effective drug permeation through nasal mucosa without causing harm. Moreover, experiments on neuronal cells exposed to oxidative stress (H2O2- induced) showcased significant neuroprotection conferred by chrysin and its formulations. These treatments exhibited notable enhancements in cell viability and reduced instances of apoptosis and necrosis, compared to the control group. The formulations exhibited neuroprotective properties by mitigating oxidative damage through mechanisms, like free radical scavenging and restoration of antioxidant enzyme activity. Conclusion: In conclusion, this developed In situ gel formulation presents a promising novel nasal delivery system for PD therapy. By addressing challenges related to drug properties and administration route, it holds the potential to enhance treatment outcomes and improve the quality of life for individuals with Parkinson's disease.