Mukkukada Ravi Rajeev, Mani Athira, Rahim Suriya, Anirudhan Thayyath Sreenivasan
Department of Chemistry, School of Physical and Mathematical Sciences, Research Centre, University of Kerala, Kariavattom, Trivandrum 695 581, India.
ACS Appl Mater Interfaces. 2024 Sep 25;16(38):50407-50429. doi: 10.1021/acsami.4c11373. Epub 2024 Sep 11.
Modern drug delivery research focuses on developing biodegradable nanopolymer systems. The present study proposed a polymer-based composite nanogel as a transdermal drug delivery system for the pH-responsive targeted and controlled delivery of anticancer drug doxorubicin (DOX). Nanogels have properties of both hydrogels and nanomaterials. The β-cyclodextrin-based nanogels can enhance the loading capacity of poorly soluble drugs and promote a sustained drug release. The β-cyclodextrin-grafted methacrylic acid conjugated hyaluronic acid composite nanogel was successfully synthesized. β-Cyclodextrin was first grafted onto methacrylic acid. The composite nanogel-based drug carrier was prepared by controlled radical polymerization (CRP) of β-cyclodextrin-grafted methacrylic acid with hyaluronic acid. The doxorubicin-loaded carrier was characterized by Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, ultraviolet-visible (UV-vis) spectroscopy, zeta potential analysis, dynamic light scattering (DLS), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The drug loading and release efficiencies were carried out at different pH levels. The maximum drug loading and encapsulation efficiencies of the synthesized final nanogel composite material at pH 8.0 were 86.44 ± 2.12 and 96.07 ± 2.01%, respectively. The DOX-loaded final material showed a 90.0 ± 2.6% release percentage of DOX at pH 5.5, whereas at pH 7.4, the release percentage of DOX was observed to be only 35.0 ± 0.3%. swelling, degradation, hemocompatibility, drug release kinetics, cytotoxicity, apoptosis, cell colocalization, skin irritation, and skin permeation studies, along with pharmacokinetic studies, were performed to prove the efficacy of the synthesized nanogel composite as a transdermal carrier for doxorubicin.
现代药物递送研究聚焦于开发可生物降解的纳米聚合物系统。本研究提出了一种基于聚合物的复合纳米凝胶作为透皮给药系统,用于对pH响应的抗癌药物阿霉素(DOX)的靶向和控释。纳米凝胶兼具水凝胶和纳米材料的特性。基于β-环糊精的纳米凝胶可提高难溶性药物的载药量并促进药物持续释放。成功合成了β-环糊精接枝甲基丙烯酸共轭透明质酸复合纳米凝胶。首先将β-环糊精接枝到甲基丙烯酸上。通过β-环糊精接枝甲基丙烯酸与透明质酸的可控自由基聚合(CRP)制备了基于复合纳米凝胶的药物载体。通过傅里叶变换红外(FTIR)光谱、核磁共振(NMR)光谱、紫外可见(UV-vis)光谱、zeta电位分析、动态光散射(DLS)、扫描电子显微镜(SEM)和透射电子显微镜(TEM)对载阿霉素的载体进行了表征。在不同pH水平下进行了药物载量和释放效率研究。合成的最终纳米凝胶复合材料在pH 8.0时的最大药物载量和包封效率分别为86.44±2.12%和96.07±2.01%。载DOX的最终材料在pH 5.5时DOX的释放率为90.0±2.6%,而在pH 7.4时,DOX的释放率仅为35.0±0.3%。进行了溶胀、降解、血液相容性、药物释放动力学、细胞毒性、凋亡、细胞共定位、皮肤刺激性和皮肤渗透性研究以及药代动力学研究,以证明合成的纳米凝胶复合材料作为阿霉素透皮载体的有效性。