Department of Pharmaceutics, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran.
Department of Pharmacology & Toxicology, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran.
Biomed Res Int. 2021 Apr 28;2021:6619195. doi: 10.1155/2021/6619195. eCollection 2021.
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.
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, release behavior, differential scanning calorimetry (DSC), and powder X-ray diffractometry (P-XRD) studies and cytotoxicity studies were assessed.
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.
Our study suggests that PPZ-SLNs can make a promising vehicle for a suitable therapy of schizophrenia for the oral drug delivery system.
奋乃静（PPZ）作为一种典型的抗精神病药物，在治疗精神分裂症方面与非典型抗精神病药物具有相同的疗效。尽管具有亲脂性，但由于口服后会发生首过代谢，PPZ 的生物利用度有限。本研究基于不同因素（包括脂质和表面活性剂的用量）制备并优化了载有 PPZ 的固体脂质纳米粒（PPZ-SLNs），旨在开发合适且安全的新型 PPZ 口服剂型。
采用溶剂乳化-蒸发法，以大豆卵磷脂、甘油单硬脂酸酯（GMS）和吐温 80 为原料制备 SLNs。采用 Box-Behnken 设计法进行统计优化，以获得粒径、包封率和 Zeta 电位优化的配方。同时，还进行了透射电子显微镜、释放行为、差示扫描量热法（DSC）和粉末 X 射线衍射（P-XRD）研究以及细胞毒性研究。
优化结果表明，各种辅料对 SLN 特性有显著影响。我们的研究结果表明，优化后的 PPZ-SLN 的平均粒径、Zeta 电位和包封率分别为 104±3.92nm、-28±2.28mV 和 83%±1.29%。PPZ-SLN 的药物释放在 48 小时内观察到超过 90%，强调了持续释放模式。DSC 和 P-XRD 研究表明，PPZ-SLN 呈无定形态。傅里叶变换红外光谱（FTIR）显示药物与脂质之间无不相容性。细胞毒性研究表明，对 HT-29 细胞培养无明显细胞毒性。
本研究表明，PPZ-SLNs 可为精神分裂症的口服药物递送系统提供一种有前途的合适治疗方法。
