Development of Perphenazine-Loaded Solid Lipid Nanoparticles: Statistical Optimization and Cytotoxicity Studies.

Parisa Abbasi Farsani,Seyed Sajad Oliaei,Mojdeh Mohammadi,Reza Mahjub,Mohammad Mehdi Mahboobian,Manish K Chourasia

doi:10.1155/2021/6619195

Abstract

Objective Perphenazine (PPZ), as a typical antipsychotic medical substance, has the same effectiveness compared to atypical antipsychotic medications for the treatment of schizophrenia. Despite the lipophilic essence, PPZ encounters limited bioavailability caused by the first-pass metabolism following oral administration. In the present study, PPZ-containing solid lipid nanoparticles (PPZ-SLNs) were prepared and optimized based on different factors, including lipid and surfactant amount, to develop appropriate and safe novel oral dosage forms of PPZ. Methods The solvent emulsification-evaporation method was utilized to form SLNs by using soybean lecithin, glycerol monostearate (GMS), and Tween 80. Statistical optimization was done by the Box-Behnken design method to achieve formulation with optimized particle size, entrapment efficiency, and zeta potential. Also, transmission electron microscopy, in vitro release behavior, differential scanning calorimetry (DSC), and powder X-ray diffractometry (P-XRD) studies and cytotoxicity studies were assessed. Results Optimization exhibited the significant effect of various excipients on SLN characteristics. Our finding indicated that the mean particle size, zeta potential, and entrapment efficiency of optimized PPZ-SLN were, respectively, 104 ± 3.92 nm, −28 ± 2.28 mV, and 83% ± 1.29. Drug release of PPZ-SLN was observed to be greater than 90% for 48 h that emphasized a sustained-release pattern. The DSC and P-XRD studies revealed the amorphous state of PPZ-SLN. FTIR spectra showed no incompatibility between the drug and the lipid. Performing cytotoxicity studies indicated no significant cytotoxicity on HT-29 cell culture. Conclusion Our study suggests that PPZ-SLNs can make a promising vehicle for a suitable therapy of schizophrenia for the oral drug delivery system.

Highlights

Schizophrenia is a debilitating disorder with heterogeneous symptoms that can cause various social, mental, and functional impairments [1]
Penicillin-streptomycin (1%), Phosphate-Buffered Saline (PBS), dimethyl sulfoxide (DMSO), Roswell Park Memorial Institute (RPMI), methylthiazolyldiphenyl-tetrazolium bromide (MTT), Fetal Bovine Serum (FBS), and trypsin were all obtained from Sigma-Aldrich (Wisconsin, United States)
Design-Expert®software was utilized to evaluate the effects of independent variables, including the concentration of Tween 80, amounts of glycerol monostearate (GMS), and amounts of lecithin, on the dependent variables, including size, zeta potential, and EE% of nanoparticles using Box-Behnken response surface methodology

Summary

Introduction

Schizophrenia is a debilitating disorder with heterogeneous symptoms that can cause various social, mental, and functional impairments [1]. For the last two decades, the disease has been categorized as one of the leading causes of disability in human life [2]. Perphenazine (PPZ), as a typical antipsychotic, is a lipophilic phenothiazine derivative compound, with a partition coefficient of 4.2 and aqueous solubility of less than 0.1 mg/ml which is mainly metabolized through hepatic pathways. These characteristics result in low bioavailability through oral administration [6,7,8,9].

Methods

Results

Conclusion