Pharmaceutics and Industrial Pharmacy Department, Faculty of Pharmacy, Beni- Suef University, Beni Suef, Egypt.
Pharmaceutics and Clinical Pharmacy Department, Faculty of Pharmacy, Nahda University, Beni Suef, Egypt.
Int J Nanomedicine. 2020 Mar 6;15:1517-1535. doi: 10.2147/IJN.S238709. eCollection 2020.
Dapoxetine HCl (DH), a selective serotonin reuptake inhibitor, may be useful for the treatment of rheumatic arthritis (RA). The purpose of this study was to investigate the therapeutic efficacy of transdermal delivery of DH in transethosome nanovesicles (TENVs). This novel delivery of DH may overcome the drawbacks associated with orally administered DH and improve patient compliance.
DH-TENV formulations were prepared using an injection- sonication method and optimized using a 3 Box-Behnken-design with Design Expert software. The TENV formulations were assessed for entrapment efficiency (EE-%), vesicle size, zeta potential, in vitro DH release, and skin permeation. The tolerability of the optimized DH-TENV gel was investigated using a rat skin irritation test. A pharmacokinetic analysis of the optimized DH-TENV gel was also conducted in rats. Moreover, the anti-RA activity of the optimized DH-TENV gel was assessed based on the RA-specific marker anti-cyclic cirtullinated peptide antibody (anti-CCP), the cartilage destruction marker cartilage oligomeric matrix protein (COMP) and the inflammatory marker interleukin-6 (IL-6). Level of tissue receptor activator of nuclear factor kappa-Β ligand (RANKL) were also assessed.
The optimized DH-TENV formulation involved spherical nanovesicles that had an appropriate EE- % and skin permeation characteristic. The DH-TENV gel was well tolerated by rats. The pharmacokinetics analysis showed that the optimized DH-TENV gel boosted the bioavailability of the DH by 2.42- and 4.16-fold compared to the oral DH solution and the control DH gel, respectively. Moreover, it significantly reduced the serum anti-CCP, COMP and IL-6 levels and decreased the RANKL levels. Furthermore, the DH-TENV gel attenuated histopathological changes by almost normalizing the articular surface and synovial fluid.
The results indicate that DH-TENVs can improve transdermal delivery of DH and thereby alleviate RA.
盐酸达泊西汀（DH）是一种选择性 5-羟色胺再摄取抑制剂，可能对治疗类风湿关节炎（RA）有用。本研究的目的是研究 DH 经皮传递到 Transethosome 纳米囊泡（TENV）中的治疗效果。这种新型的 DH 传递方式可能克服与口服 DH 相关的缺点，提高患者的顺应性。
使用注射-超声法制备 DH-TENV 制剂，并使用 Design Expert 软件的 3 箱-贝肯设计进行优化。评估 TENV 制剂的包封效率（EE-%）、囊泡大小、zeta 电位、体外 DH 释放和皮肤渗透。使用大鼠皮肤刺激性试验研究优化的 DH-TENV 凝胶的耐受性。还在大鼠中进行了优化的 DH-TENV 凝胶的药代动力学分析。此外，根据 RA 特异性标志物抗环瓜氨酸肽抗体（抗-CCP）、软骨破坏标志物软骨寡聚基质蛋白（COMP）和炎症标志物白细胞介素-6（IL-6）评估优化的 DH-TENV 凝胶的抗 RA 活性。还评估了组织核因子 kappa-B 配体受体激活剂（RANKL）的水平。
优化的 DH-TENV 制剂涉及具有适当 EE-%和皮肤渗透特性的球形纳米囊泡。DH-TENV 凝胶对大鼠具有良好的耐受性。药代动力学分析表明，与口服 DH 溶液和对照 DH 凝胶相比，优化的 DH-TENV 凝胶使 DH 的生物利用度分别提高了 2.42 倍和 4.16 倍。此外，它显著降低了血清抗-CCP、COMP 和 IL-6 水平，并降低了 RANKL 水平。此外，DH-TENV 凝胶通过几乎使关节表面和滑液正常化来减轻组织病理学变化。
结果表明，DH-TENVs 可以改善 DH 的经皮传递，从而缓解 RA。
