Rodriguez-Tellez Teresa G, Magaña Héctor, Cornejo-Bravo José M, Palomino-Vizcaino Giovanni, Palomino-Vizcaino Kenia
Faculty of Chemical Sciences and Engineering, Autonomous University of Baja California, University Boulevard No. 14418, Otay Mesa, Tijuana 22390, Mexico.
Faculty of Health Sciences, Autonomous University of Baja California, University Boulevard No. 1000, Tijuana 22260, Mexico.
Gels. 2024 Dec 7;10(12):806. doi: 10.3390/gels10120806.
This study aims to design microgels that are thermo- and pH-sensitive for controlled doxorubicin (Dox) release in response to tumor microenvironment changes. N-isopropylacrylamide (NIPAAm) is widely used for thermoresponsive tumor-targeted drug delivery systems for the release of therapeutic payloads in response to temperature changes. Herein, a NIPAAm microgel (MP) that is responsive to temperature and pH was designed for the smart delivery of Dox. MP was made from NIPAAm, and polyethylene glycol methyl ether methacrylate (PEGMA) was copolymerized with 5%, 10%, or 15% mol of methacryloylamido hexanoic acid, (CAM5) an amphiphilic acid. We characterized the microgels using FTIR-ATR, DLS, and FESEM. The MP 10% CAM5 exhibited a particle size of 268 nm, with a transition temperature of 44 °C. MP had a drug loading capacity of 13% and entrapment efficiency of 87%. Nearly 100% of the Dox was released at pH 5 and 42 °C, compared to 30% at pH 7.4 and 37 °C. MP 10% CAM5 showed cytocompatibility in HeLa cells using the MTT assay. However, the cell viability assay showed that dox-MP was twice as effective as free Dox. Specifically, 3 μg/mL of free Dox resulted in 74% cell viability, while the same doses of Dox in NP reduced it to 35%. These results are promising for the future tumor-targeted delivery of antineoplastic-drugs, as they may reduce the side effects of Dox.
本研究旨在设计对温度和pH敏感的微凝胶，以便根据肿瘤微环境变化实现阿霉素（Dox）的可控释放。N-异丙基丙烯酰胺（NIPAAm）广泛用于热响应性肿瘤靶向给药系统，以根据温度变化释放治疗药物。在此，设计了一种对温度和pH有响应的NIPAAm微凝胶（MP）用于Dox的智能递送。MP由NIPAAm制成，聚乙二醇甲基醚甲基丙烯酸酯（PEGMA）与5%、10%或15%摩尔的甲基丙烯酰氨基己酸（CAM5，一种两亲酸）共聚。我们使用傅里叶变换红外衰减全反射光谱（FTIR-ATR）、动态光散射（DLS）和场发射扫描电子显微镜（FESEM）对微凝胶进行了表征。含10% CAM5的MP粒径为268 nm，转变温度为44℃。MP的载药量为13%，包封率为87%。在pH 5和42℃时，近100%的Dox释放，而在pH 7.4和37℃时为30%。使用MTT法检测发现含10% CAM5的MP在HeLa细胞中具有细胞相容性。然而，细胞活力检测表明，载药MP的效果是游离Dox的两倍。具体而言，3μg/mL的游离Dox导致74%的细胞活力，而相同剂量的NP中的Dox将其降低至35%。这些结果对于未来抗肿瘤药物的肿瘤靶向递送很有前景，因为它们可能会降低Dox的副作用。
