Fabrication and in vivo evaluation of ligand appended paclitaxel and artemether loaded lipid nanoparticulate systems for the treatment of NSCLC: A nanoparticle assisted combination oncotherapy

Abstract

Schizophrenia is a chronic and severe mental disorder that affects a person’s thoughts, feelings, and behavior. The treatment of schizophrenic patients is a challenging task for the caregivers and the doctors. Clozapine, the first atypical antipsychotic drug, is proved to be the most significant medication for the treatment of schizo phrenia. However, the oral bioavailability of clozapine is only about 27% as it undergoes extensive hepatic first pass metabolism. Taking this into consideration, the transdermal patch of clozapine was developed in order to bypass the biotransformation of clozapine and thereby enhance its bioavailability. The present research work was intended to develop and optimize the transdermal adhesive patch of clozapine using a 3-level 2-factor experimental design. Optimized formulation was evaluated for the physicochemical characterization, fourier transform infrared, differential scanning calorimetry, permeability enhancement potential by ex vivo, skin irritation, in vivo pharmacokinetics, and stability studies. The results of the optimized formulation (F5) showed the peel strength of 428 ± 3.43 cN/cm, the flux of 106.20 ± 1.21 (μg/h/cm2 ), and % drug content of 99.53 ± 0.42% which was stable up to six months in accelerated condition. As per the Draize score method, the optimized transdermal patch of clozapine was found to be free from skin irritation. The pharmacokinetic result had shown the bioavailability of clozapine improved about 2.23 fold after transdermal drug delivery when compared with the oral marketed formulation. The results of the study revealed that the developed transdermal patch of clo zapine can be a promising alternative that provides effective management of schizophrenia in terms of improved patient compliance.