Hashem Heba M, Motawea Amira, Kamel Ayman H, Bary E M Abdel, Hassan Saad S M
Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.
Pharmaceutics Department, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.
Sci Rep. 2022 Oct 27;12(1):18037. doi: 10.1038/s41598-022-22878-7.
Recently, drug-controlled release nanotechnology has gained special attention in biomedicine. This work focuses on developing novel electrospun polymeric nanofibers (NFs) for buccal delivery of VEN to avoid the hepatic metabolism and enzymatic degradation in the GIT and develop an effective control of drug release. The optimized NFs were obtained by blending polylactic acid (PLA), and poly (ɛ-caprolactone) (PCL) fixed at a ratio of 1:1. It was characterized for morphology, drug-loading, FTIR, XRD, DSC, and in vitro drug release. Ex vivo permeability of the blend NFs was assessed using chicken pouch mucosa compared to VEN suspension, followed by histopathological examination. Further, the cytotoxic effect in three different cell lines using WST-1 assay. SEM morphologies refer to defect-free uniform NFs of PLA, PCL, and PLA/PCL mats. These fibers had a diameter ranging from 200 to 500 nm. The physico-thermal characterization of NFs depicted that the drug was successfully loaded and in an amorphous state in the PLA/PCL NFs. In vitro release of NFs substantiated a bi-phasic profile with an initial burst release of about 30% in the initial 0.5 h and a prolonged cumulative release pattern that reached 80% over 96 h following a non-Fickian diffusion mechanism. Ex vivo permeation emphasizes the major enhancement of the sustained drug release and the noticeable decrease in the permeability of the drug from NFs. Cytotoxicity data found that IC of VEN alone was 217.55 μg/mL, then VEN-NFs recorded an IC value of 250.62 μg/mL, and plain NFs showed the lowest toxicity and IC 440.48 μg/mL in oral epithelial cells (OEC). Histopathology and cell toxicity studies demonstrated the preserved mucosal architecture and the preclinical safety. The developed PLA/PCL NFs can be promising drug carriers to introduce a step-change in improved psychiatric treatment healthcare.
近年来，药物控释纳米技术在生物医学领域受到了特别关注。这项工作的重点是开发用于口腔递送文拉法辛（VEN）的新型电纺聚合物纳米纤维（NFs），以避免肝脏代谢和胃肠道中的酶降解，并实现对药物释放的有效控制。通过以1:1的比例混合聚乳酸（PLA）和聚（ε-己内酯）（PCL）获得了优化的纳米纤维。对其进行了形态学、载药量、傅里叶变换红外光谱（FTIR）、X射线衍射（XRD）、差示扫描量热法（DSC）和体外药物释放表征。与VEN悬浮液相比，使用鸡嗉囊黏膜评估了共混纳米纤维的体外渗透性，随后进行了组织病理学检查。此外，使用WST-1测定法研究了在三种不同细胞系中的细胞毒性作用。扫描电子显微镜（SEM）形态学显示PLA、PCL和PLA/PCL垫的纳米纤维无缺陷且均匀。这些纤维的直径范围为200至500纳米。纳米纤维的物理热表征表明，药物成功负载在PLA/PCL纳米纤维中且呈无定形状态。纳米纤维的体外释放呈现双相特征，在最初的0.5小时内有大约30%的初始突释，随后按照非菲克扩散机制在96小时内累计释放达到80%的延长释放模式。体外渗透强调了药物持续释放的显著增强以及纳米纤维中药物渗透性的明显降低。细胞毒性数据发现，单独的VEN的半数抑制浓度（IC）为217.55微克/毫升，然后VEN-纳米纤维的IC值为250.62微克/毫升，普通纳米纤维在口腔上皮细胞（OEC）中显示出最低的毒性，IC为440.48微克/毫升。组织病理学和细胞毒性研究证明了黏膜结构的保留和临床前安全性。所开发的PLA/PCL纳米纤维有望成为药物载体，为改善精神治疗医疗带来重大变革。
