LA67脂质体载荷载能温敏水凝胶及主动定位用于通过肿瘤周围注射高效治疗瘢痕病变。
LA67 Liposome-Loaded Thermo-Sensitive Hydrogel with Active Targeting for Efficient Treatment of Keloid via Peritumoral Injection.
发表日期:2023 Aug 18
作者:
Hongshuang Wan, Shuangqing Wang, Chuying Li, Bowen Zeng, Hao Wu, Chao Liu, Liqing Chen, Mingji Jin, Wei Huang, Yingda Zang, Dongming Zhang, Zhonggao Gao, Zhehu Jin
来源:
Pharmaceutics
摘要:
疤痕增生是一种表皮异常纤维增生的良性肿瘤。治疗疤痕增生已成为临床上的重大挑战,寻找新的治疗方法和药物变得至关重要。在本研究中,我们开发了一种LA67脂质体载药热敏水凝胶(LA67-RL-Gel),通过肿瘤周围注射具有活性靶向作用的方式用于治疗疤痕增生,并探究其抗疤痕增生机制。首先,我们制备了载有LA67的Arg-Gly-Asp(RGD)肽修饰的脂质体(LA67-RL),粒径为105.9 nm,ζ电位为-27.4 mV,包封率为89.6 ± 3.7%。然后,我们通过聚氧化丙烯酸钠407和聚氧化丙烯酸钠188构建了载有LA67-RL的热敏水凝胶。通过Box-Behnken设计优化了配方,全面评估了成分比例对水凝胶质量的影响。最优配方为20.7% P407和2.1% P188,37 °C下凝胶化时间为9.5秒。LA67-RL-Gel在pH 6.5磷酸盐缓冲液中缓慢释放了92.2 ± 0.8%的LA67,持续72小时。LA67-RL-Gel增加了与KF细胞的黏附,增强了摄取,促进了KF细胞凋亡,抑制了细胞增殖,减少了α-SMA含量,降低了胶原I、胶原III和纤维连接蛋白沉积,抑制了血管生成,调节了疤痕增生微环境,最终发挥了抗疤痕增生的作用。总之,这种简单、低成本、高效的抗疤痕增生脂质体水凝胶为治疗疤痕增生提供了一种新的方法,值得进一步开发。
A keloid is a benign tumor manifested as abnormal fibroplasia on the surface of the skin. Curing keloids has become a major clinical challenge, and searching for new treatments and medications has become critical. In this study, we developed a LA67 liposome-loaded thermo-sensitive hydrogel (LA67-RL-Gel) with active targeting for treating keloids via peritumoral injection and explored the anti-keloid mechanism. Firstly, Arg-Gly-Asp (RGD) peptide-modified liposomes (LA67-RL) loaded with LA67 were prepared with a particle size of 105.9 nm and a Zeta potential of -27.4 mV, and an encapsulation efficiency of 89.6 ± 3.7%. We then constructed a thermo-sensitive hydrogel loaded with LA67-RL by poloxamer 407 and 188. The formulation was optimized through the Box-Behnken design, where the impact of the proportion of the ingredients on the quality of the hydrogel was evaluated entirely. The optimal formulation was 20.7% P407 and 2.1% P188, and the gelation time at 37 °C was 9.5 s. LA67-RL-Gel slowly released 92.2 ± 0.8% of LA67 at pH 6.5 PBS for 72 h. LA67-RL-Gel increased adhesion with KF cells; increased uptake; promoted KF cells apoptosis; inhibited cell proliferation; reduced α-SMA content; decreased collagen I, collagen III, and fibronectin deposition; inhibited angiogenesis; and modulated the keloid microenvironment, ultimately exerting anti-keloid effects. In summary, this simple, low-cost, and highly effective anti-keloid liposome hydrogel provides a novel approach for treating keloids and deserves further development.