Targeted neurotherapy: evaluating olanzapine-loaded bilosomes in a cuprizone-induced schizophrenia model

The study aimed to develop and evaluate the efficacy of olanzapine (Olz) loaded bilosomes (BLs) for the treatment of schizophrenia. Olz-loaded bilosomes (Olz-Bls) were prepared adopting thin-film hydration method and evaluated for entrapment efficiency (EE%), vesicle size (VS) and zeta potential (ZP) to select the optimum formulation. In-vitro release study was performed to evaluate the release pattern of drug from the selected formulation (Olz-Bls₇). In-vivo studies were conducted on cuprizone-induced schizophrenia in mice. Rats were divided into five groups. Group 1: represented negative control group, Group 2: cuprizone group (CPZ; 0.2 % in diet for 6  weeks) and represented positive control group, whereas Groups 3, 4 and 5 received orally drug-free Bls, free-Olz and Olz-BLs. Vesicles exhibited high EE% ranging from 51 ± 5.5 to 78.5 ± 4.8 %, their size ranged between 667 ± 36.1 to 838 ± 24.8 nm and ZP values were high denoting good stability. Release of Olz from Olz-Bls₇ was biphasic. In vivo experiments confirmed the efficiency of Olz-BLs in the alleviation of schizophrenia. Olz-Bls₇ increased Myelin basic protein (MBP) elevating Open field crossing count and Y-maze alternation. In addition, Olz-Bls₇ decreased IL-6 neuroinflammatory mediator, dopamine and glutamate, elevated N-methyl-D-aspartate receptor (NMDA) and neuroregulin 1 (NRG1) brain contents and alleviated nuclear pyknosis and neurons degeneration as compared to cuprizone control group and free Olz. Therefore, OLz-BLs can be considered as a new therapeutic approach for enhancing the efficacy of OLz for the treatment of schizophrenia induced by cuprizone via inhibiting demyelination, behavioral abnormalities and neurotransmitters disturbance.