In vitro and in vivo evaluation of an ionic sensitive in situ gel containing nanotransfersomes for aripiprazole nasal delivery

In the current study, a composite in-situ gel formulation containing aripiprazole (APZ) loaded transfersomes (TFS) was developed for the intranasal brain targeting of APZ. APZ loaded TFS were prepared by applying the film hydration method and optimized using an irregular factorial design. The prepared formulations were optimized based on different parameters including particle size, polydispersity index (PdI), zeta potential, encapsulation efficiency (EE) and release efficiency (RE). The optimized APZ-TFS were distributed in an ion-triggered deacetylated gellan gum solution (APZ-TFS-Gel) and evaluated in terms of pH, gelling time, rheological properties and in-vitro release study. The therapeutic efficacy of the best APZ-TFS-Gel was then tested in the mice model of schizophrenia induced by ketamine by evaluating various behavioral parameters. The optimized formulation showed the particle size of 72.12 +/- 0.72 nm, the PdI of 0.19 +/- 0.07, the zeta potential of -55.56 +/- 1.9 mV, the EE of 97.06 +/- 0.10%, and the RE of 70.84 +/- 1.54%. The in-vivo results showed that compared with the other treatment groups, there was a considerable increase in swimming and climbing time and a decrease in locomotors activity and immobility time in the group receiving APZ-TFS-Gel. Thus, APZ-TFS-Gel was found to have desirable characteristics for therapeutic improvement.

Automated summary

In this study, a composite in-situ gel formulation containing APZ loaded TFS was developed and optimized for the intranasal brain targeting of APZ, showing promising therapeutic effects for schizophrenia treatment. The optimized formulation demonstrated excellent targeting and efficacy in vivo, with significant behavioral improvements observed.