Development, characterization and pharmacokinetic evaluation of selegiline HCl loaded cubosomal thermoreversible mucoadhesive gel for nose to brain delivery

Abstract

Selegiline HCl (SGH) is MAO-B inhibitor with limited bioavailability due to extensive hepatic metabolism. Thus, this work aims to formulate and evaluate SGH loaded intranasal thermoreversible cubosomal gel in order to enhance its bioavailability and ensure efficient brain targeting. Experimental design and Artificial Neural Network (ANN) were explored to optimize the formulation. Gellan gum and konjac gum were used as gelling agent and mucoadhesive agent respectively to formulate mucoadhesive in situ nasal gel. Optimized formulation of SGH loaded cubosomal dispersion exhibits average particle size (166.8 ± 3.12 nm), entrapment efficiency (72.85 ± 1.50 %), and drug release at 6 h (89.15 ± 1.04 %). In vitro drug release analysis demonstrated the sustained release pattern. In vivo pharmacokinetic studies in Swiss Albino mice showed approximately 1.90-fold increase in Cmax and AUC(0-t) in brain after intranasal administration. The Cmax and AUC for drug solution was found to be 4.3828 ± 0.02 ng/mL, 19.4166 ± 0.06 ng min/mL and for cubosomal gel it was 11.7665 ± 0.32 ng/mL, 36.9216 ± 0.41 ng min/mL respectively. Furthermore, the stability study was executed for estimation of shelf life of optimized formulation. The shelf life of SGH loaded cubosmal gel was found to be 20.64 months which demonstrate its long-term stability. The in vitro and in vivo evaluation endorsed that the fabricated cubosomal in situ nasal gel could be the promising approach for nose to brain delivery of SGH in Parkinson's therapy.