Department of Pharmaceutics, School of Pharmacy and Novel Drug Delivery Systems Research Centre, Isfahan University of Medical Sciences, Isfahan, Iran.
Department of Pharmaceutics, School of Pharmacy and Novel Drug Delivery Systems Research Centre, Isfahan University of Medical Sciences, Isfahan, Iran.
Int J Pharm. 2022 Aug 25;624:122036. doi: 10.1016/j.ijpharm.2022.122036. Epub 2022 Jul 19.
In the present study, gefitinib loaded cellulose acetate butyrate nanoparticles (Gnb-NPs) were prepared and then incorporated into thermo-sensitive chitosan/β-glycerophosphate hydrogels for intratumoral administration in mice bearing breast cancer. Accordingly, Gnb-NPs were prepared using the solvent evaporation process and optimized by applying a two-level fractional factorial design. Properties of NPs, including particle size, zeta potential (ZP), polydispersity index (PdI), encapsulation efficiency (EE) % and drug loading (DL) %, were investigated; the optimized Gnb-NPs were then loaded in chitosan hydrogels (Gnb-NPs-Hydrogel). The formulated Gnb-NPs-Hydrogel was assessed in terms of gelling time, release behavior, injectability, swelling and degradation behavior. The anti-cancer efficacy of Gnb-NPs-Hydrogel was evaluated in vitro against the 4 T1 breast cancer cell line and in vivo in breast tumor bearing mice. The optimized formulation showed spherical particles with the size of 156.50 ± 2.40 nm, PdI of 0.20 ± 0.002, ZP of -4.90 ± 0.04 mV, EE of 99.77 ± 0.09 % and DL of 20.59 ± 0.05 %. Incorporating Gnb-NPs into the hydrogel led to the decrease of the drug release rate. Gnb-NPs-Hydrogel displayed a greater cytotoxic effect in comparison to the free Gnb and Gnb-Hydrogel in 4 T1 cancer cells. Furthermore,intratumorallyinjectedGnb-NPs-Hydrogel showed the strongest antitumor efficacy in vivo. The superior performance of Gnb-NPs-Hydrogel, thus, demonstrated its potential for the treatment of breast cancer.
在本研究中，制备了吉非替尼负载醋酸丁酸纤维素纳米粒（Gnb-NPs），然后将其掺入载体温敏壳聚糖/β-甘油磷酸盐水凝胶中，用于荷乳腺癌小鼠的瘤内给药。因此，采用溶剂蒸发法制备 Gnb-NPs，并通过应用 2 水平部分因子设计进行优化。考察了 NPs 的性质，包括粒径、Zeta 电位（ZP）、多分散指数（PdI）、包封效率（EE）%和载药量（DL）%；然后将优化的 Gnb-NPs 载入壳聚糖水凝胶（Gnb-NPs-Hydrogel）中。从凝胶时间、释放行为、可注射性、溶胀和降解行为等方面评估了配方的 Gnb-NPs-Hydrogel。体外评价 Gnb-NPs-Hydrogel 对 4T1 乳腺癌细胞系的抗癌疗效，体内评价荷乳腺癌小鼠的疗效。优化后的制剂呈球形颗粒，粒径为 156.50±2.40nm，PdI 为 0.20±0.002，ZP 为-4.90±0.04mV，EE 为 99.77±0.09%，DL 为 20.59±0.05%。将 Gnb-NPs 掺入水凝胶中会降低药物释放速率。与游离 Gnb 和 Gnb-Hydrogel 相比，Gnb-NPs-Hydrogel 在 4T1 癌细胞中表现出更强的细胞毒性作用。此外，瘤内注射 Gnb-NPs-Hydrogel 表现出最强的体内抗肿瘤疗效。因此，Gnb-NPs-Hydrogel 的优越性能表明其在乳腺癌治疗中的潜力。
