儿茶酚-O-甲基转移酶抑制剂（iCOMT），例如恩他卡朋，已成功用于治疗帕金森病的震颤相关症状。然而，iCOMT 半衰期短且口服生物利用度差。纳米药物输送系统经常被用来克服这种类型的挫折。因此，恩他卡朋通过纳米沉淀过程被封装在基于聚乙二醇化聚乳酸-乙醇酸 (PLGA) 的纳米颗粒 (NP) 中，并使用溶剂乳化/蒸发方法被封装在聚乙二醇化纳米结构脂质载体 (NLC) 中。两种纳米制剂均呈现亚 200 nm 群体，zeta 电位 (ZP) 值接近 -30 mV，并在不同 pH 下表现出稳定性，同时保持其物理化学性质基本完整，仅呈现表面电荷（ZP 值）变化，表明它们的相互作用。两种纳米制剂都与粘蛋白相互作用，预计口服和局部给药具有良好的渗透性和生物利用度。封装恩他卡朋的冻干 PLGA NP，其中使用 3% 浓度的 2-羟丙基-β-环糊精 (HPβCD) 作为冷冻保护剂 (HP-PLGA@Ent)，在人肝细胞癌 (HepG2)、人肝癌中未观察到细胞毒性作用神经母细胞瘤 (SH-SY5Y) 或人上皮结直肠腺癌 (Caco-2) 细胞系。相反，封装恩他卡朋的 NLC (W-NLCs@Ent) 对 HepG2 细胞系表现出细胞毒性作用，这可能是由于细胞内脂质积累或储存所致。使用 3-BTD 作为 COMT 探针，两种纳米制剂在 HepG2 细胞中均保持 COMT 抑制作用。对于所开发的纳米制剂，在单层和共培养模型（分别为 Caco-2 和 Caco-2/HT29-MTX）中观察到恩他卡朋渗透性增加。总的来说，这项工作表明，封装在不同纳米载体中的恩他卡朋可能是解决恩他卡朋挫折的一种刺激性替代方案，因为它们改善了其理化性质和渗透性，同时仍保持 COMT 抑制活性。

Catechol-O-methyltransferase inhibitors (iCOMT), such as entacapone, have been successfully employed to treat tremor-related symptoms of Parkinson's disease. However, iCOMT has been associated with a short half-life and poor oral bioavailability. Nanobased drug delivery systems have often been used to overcome this type of setbacks. Therefore, entacapone was encapsulated in PEGylated poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) via a nanoprecipitation process, as well as in PEGylated nanostructured lipid carriers (NLCs) using a solvent emulsification/evaporation method. Both nanoformulations presented sub-200 nm populations, with zeta-potential (ZP) values close to -30 mV, and showed stability at different pHs, while maintaining their physicochemical properties mostly intact, presenting only a change in their superficial charge (ZP values), indicating their interaction. Both nanoformulations presented interaction with mucins, which anticipates good permeation and bioavailability for oral and topical administration. No cytotoxic effects were observed for lyophilized PLGA NPs encapsulating entacapone, in which 2-hydroxypropyl-ß-cyclodextrin (HPβCD) was used as a cryoprotectant at 3% concentration (HP-PLGA@Ent), in human hepatocellular carcinoma (HepG2), human neuroblastoma (SH-SY5Y), or human epithelial colorectal adenocarcinoma (Caco-2) cell lines. Conversely, NLCs encapsulating entacapone (W-NLCs@Ent) presented cytotoxic effects on the HepG2 cell line, likely due to intracellular lipid accumulation or storage. Both nanoformulations maintained a COMT inhibition effect in HepG2 cells, using 3-BTD as the COMT probe. An increase of entacapone permeability in both monolayer and coculture models (Caco-2 and Caco-2/HT29-MTX, respectively) was observed for the developed nanoformulations. Overall, this work shows that encapsulated entacapone in different nanocarriers could be a stimulating alternative to solve entacapone setbacks, since they improve its physicochemical properties and permeability while still maintaining the COMT inhibitory activity.