Mohan Anandhu, Santhamoorthy Madhappan, Phan Thi Tuong Vy, Kim Seong-Cheol
Department of Nano Science and Technology Convergence, General Graduate School, Gachon University, 1342 Seongnam-Daero, Sujeong-gu, Seongnam-si 13120, Gyeonggi-do, Republic of Korea.
School of Chemical Engineering, Yeungnam University, Gyeongsan 38541, Gyeongbuk, Republic of Korea.
Gels. 2024 Mar 7;10(3):184. doi: 10.3390/gels10030184.
The regulated and targeted administration of hydrophobic and hydrophilic drugs is both promising and challenging in the field of drug delivery. Developing a hydrogel which is responsive to dual stimuli is considered a promising and exciting research area of study. In this work, melamine functionalized poly-N-isopropyl acrylamide-co-glycidyl methacrylate copolymer has been developed by copolymerizing glycidyl methacrylate (GMA) monomer with N-isopropyl acrylamide (NIPAm) and further functionalized with melamine units (pNIPAm-co-pGMA-Mela). The prepared pNIPAm-co-pGMA-Mela copolymer hydrogel was characterized using various characterization techniques, including H NMR, FTIR, SEM, zeta potential, and particle size analysis. A hydrophobic drug (ibuprofen, Ibu) and hydrophilic drug (5-fluorouracil, 5-Fu) were selected as model drugs. Dual pH and temperature stimuli-responsive drug release behavior of the pNIPAm-co-pGMA-Mela hydrogel was evaluated under different pH (pH 7.4 and 4.0) and temperature (25 °C, 37 °C, and 45 °C) conditions. Furthermore, the in vitro biocompatibility of the developed pNIPAm-co-pGMA-Mela copolymer hydrogel was determined on MDA-MB-231 cells. The pH and temperature-responsive drug delivery study results reveal that the pNIPAm-co-pGMA-Mela hydrogel system is responsive to both pH and temperature stimuli and exhibits about ~100% of Ibu and 5-Fu, respectively, released at pH 4.0/45 °C. Moreover, the MTT assay and hemocompatibility analysis results proved that the pNIPAm-co-pGMA-Mela hydrogel system is biocompatible and hemocompatible, suggesting that that it could be used for drug delivery applications. The experimental results suggest that the proposed pNIPAm-co-pGMA-Mela hydrogel system is responsive to dual pH and temperature stimuli, and could be a promising drug carrier system for both hydrophilic and hydrophobic drug delivery applications.
在药物递送领域，疏水性和亲水性药物的调控靶向给药既充满前景又具有挑战性。开发一种对双重刺激有响应的水凝胶被认为是一个有前景且令人兴奋的研究领域。在这项工作中，通过使甲基丙烯酸缩水甘油酯（GMA）单体与N-异丙基丙烯酰胺（NIPAm）共聚，然后用三聚氰胺单元进一步官能化，制备了三聚氰胺官能化的聚-N-异丙基丙烯酰胺-共-甲基丙烯酸缩水甘油酯共聚物（pNIPAm-co-pGMA-Mela）。使用多种表征技术对制备的pNIPAm-co-pGMA-Mela共聚物水凝胶进行了表征，包括核磁共振氢谱（1H NMR）、傅里叶变换红外光谱（FTIR）、扫描电子显微镜（SEM）、zeta电位和粒径分析。选择一种疏水性药物（布洛芬，Ibu）和亲水性药物（5-氟尿嘧啶，5-Fu）作为模型药物。在不同pH（pH 7.4和4.0）和温度（25℃、37℃和45℃）条件下，评估了pNIPAm-co-pGMA-Mela水凝胶的双重pH和温度刺激响应性药物释放行为。此外，在MDA-MB-231细胞上测定了所开发的pNIPAm-co-pGMA-Mela共聚物水凝胶的体外生物相容性。pH和温度响应性药物递送研究结果表明，pNIPAm-co-pGMA-Mela水凝胶体系对pH和温度刺激均有响应，在pH 4.0/45℃时分别释放约100%的Ibu和5-Fu。此外，MTT法和血液相容性分析结果证明，pNIPAm-co-pGMA-Mela水凝胶体系具有生物相容性和血液相容性，表明它可用于药物递送应用。实验结果表明，所提出的pNIPAm-co-pGMA-Mela水凝胶体系对双重pH和温度刺激有响应，可能是一种用于亲水性和疏水性药物递送应用的有前景的药物载体系统。
