School of Pharmacy, Wannan Medical College, Wuhu 241002, China.
Institute of Synthesis and Application of Medical Materials, Wannan Medical College, Wuhu 241002, China.
Curr Drug Deliv. 2023;20(7):919-926. doi: 10.2174/1567201819666220628094239.
Paclitaxel (PTX), voted as the promising natural medicine molecule, is widely used in the treatment of cancers. Nevertheless, its clinical application is strictly limited by its poor water solubility.
CP-MEs (Paclitaxel-coix seed oil coloaded microemulsion), a small-sized self-emulsifying nanoemulsion formed from a combination of PTX and coix seed oil (CSO), was developed in order to improve the solubility of paclitaxel and enhance anti-cervical cancer efficacy in vitro. CSO was selected as the oil phase to replace conventional organic solvents and achieve a synergistic anti-tumor effect with paclitaxel.
Pseudoternary phase diagram was applied to the study of CP-MEs formulation. CP-MEs were prepared and characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The encapsulation efficiency and drug loading efficiency (EE and LE) were detected by HPLC. MTT was adopted to evaluate the cytotoxicity of CP-MEs against HeLa cells. The cellular uptake and apoptotic ratio of CP-MEs were evaluated by flow cytometry. Notably, HeLa 3D tumor spheroid was adopted to evaluate tumor permeability of different size microemulsions as the model.
The best self-emulsifying ability was exhibited by HS 15: PEG 400 combination. The appearance of CP-MEs was clear and transparent, which exhibited a small size (30.28 ± 0.36) and a slight negative surface charge (-4.40 ± 1.13) mV. The EE and LE of CP-MEs were 98.80% and 0.978%, respectively. The cumulative release rate within 48 h of the CP-MEs was 80.21%. In cellular studies, the uptake of fluorescein isothiocyanate (FITC) labeled CP-MEs (FITC/C-MEs) was 17.86-fold higher than the free FITC group, leading to significant synergistic anticancer activity in terms of cytotoxicity and apoptosis induction in vitro. The apoptotic rate of CP-MEs treated was 1.70-fold higher than PTXtreated. Notably, the penetration of CP-MEs in the HeLa 3D tumor sphere model was enhanced, which was related to deeply penetrated microemulsion of small size mediated at the tumor site.
With the advantage of the small-sized self-emulsifying system, CP-MEs hold great potential to become an efficient nano drug delivery system for cervical cancer treatment in the clinic.
紫杉醇（PTX）作为一种有前途的天然药物分子，被广泛应用于癌症的治疗。然而，其临床应用受到其较差水溶性的严格限制。
CP-MEs（紫杉醇-薏苡仁油共载微乳）是由紫杉醇和薏苡仁油（CSO）组合形成的一种自乳化纳米乳，旨在提高紫杉醇的溶解度并增强体外抗宫颈癌疗效。CSO 被选为油相，以替代传统有机溶剂，并与紫杉醇发挥协同抗肿瘤作用。
采用伪三元相图研究 CP-MEs 的配方。通过透射电子显微镜（TEM）和动态光散射（DLS）对 CP-MEs 进行制备和表征。采用高效液相色谱法（HPLC）检测包封率和载药量（EE 和 LE）。采用 MTT 法评价 CP-MEs 对 HeLa 细胞的细胞毒性。采用流式细胞术评价 CP-MEs 的细胞摄取和凋亡率。值得注意的是，采用 HeLa 3D 肿瘤球体模型评价不同粒径微乳的肿瘤通透性。
HS15：PEG400 组合表现出最佳的自乳化能力。CP-MEs 的外观清晰透明，粒径较小（30.28±0.36），表面带轻微负电荷（-4.40±1.13）mV。CP-MEs 的 EE 和 LE 分别为 98.80%和 0.978%。CP-MEs 在 48 h 内的累积释放率为 80.21%。在细胞研究中，荧光素异硫氰酸酯（FITC）标记的 CP-MEs（FITC/C-MEs）的摄取量是游离 FITC 组的 17.86 倍，导致体外细胞毒性和凋亡诱导方面具有显著的协同抗癌活性。CP-MEs 处理组的凋亡率是 PTX 处理组的 1.70 倍。值得注意的是，CP-MEs 在 HeLa 3D 肿瘤球体模型中的穿透性增强，这与小尺寸的深入穿透微乳在肿瘤部位的介导有关。
CP-MEs 具有小尺寸自乳化系统的优势，有望成为治疗宫颈癌的高效纳米药物传递系统，在临床上得到应用。
