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功能化辣木胶作为用于阿霉素递送的pH响应纳米凝胶:合成、动力学建模及体外细胞毒性研究

Functionalized Moringa oleifera Gum as pH-Responsive Nanogel for Doxorubicin Delivery: Synthesis, Kinetic Modelling and In Vitro Cytotoxicity Study.

作者信息

Ranote Sunita, Musioł Marta, Kowalczuk Marek, Joshi Veena, Chauhan Ghanshyam S, Kumar Rakesh, Chauhan Sandeep, Kumar Kiran

机构信息

Centre of Polymer and Carbon Materials, Polish Academy of Sciences, 34. M. Curie-Skłodowska St., 41-819 Zabrze, Poland.

Department of Chemistry, Hemvati Nandan Bahuguna Garhwal University, SRT Campus, Tehri Garhwal, Srinagar 249199, Uttarakhand, India.

出版信息

Polymers (Basel). 2022 Nov 3;14(21):4697. doi: 10.3390/polym14214697.

Abstract

Environment-responsive-cum-site-specific delivery of therapeutic drugs into tumor cells is a foremost challenge for chemotherapy. In the present work, gum-based pH-responsive nanogel (MOGN) was functionalized as a doxorubicin (DOX) carrier. It was synthesized via free radical polymerization through the γ-irradiation method using acrylamide and N,N'-MBA followed by hydrolysis, sonication, and ultracentrifugation. The swelling behavior of MOGN as a function of pH was assessed using a gravimetric method that revealed its superabsorbent nature (365.0 g/g). Furthermore, MOGN showed a very high loading efficiency (98.35 %L) of DOX by MOGN. In vitro release studies revealed that DOX release from DOX-loaded MOGN was 91.92% at pH 5.5 and 12.18% at 7.4 pH, thus favorable to the tumor environment. The drug release from nanogel followed Korsmeyer-Peppas model at pH 5.5 and 6.8 and the Higuchi model at pH 7.4. Later, the efficient DOX release at the tumor site was also investigated by cytotoxicity study using cells. Thus, the synthesized nanogel having high drug loading capacity and excellent pH-triggered disintegration and DOX release performance in a simulated tumor environment could be a promising candidate drug delivery system for the targeted and controlled release of anticancer drugs.

摘要

将治疗药物以环境响应兼位点特异性的方式递送至肿瘤细胞是化疗面临的首要挑战。在本研究中,基于树胶的pH响应性纳米凝胶(MOGN)被功能化作为阿霉素(DOX)载体。它通过γ辐射法,使用丙烯酰胺和N,N'-亚甲基双丙烯酰胺,经自由基聚合反应合成,随后进行水解、超声处理和超速离心。采用重量法评估了MOGN作为pH函数的溶胀行为,结果显示其具有高吸水性(365.0 g/g)。此外,MOGN对DOX的负载效率非常高(98.35 %L)。体外释放研究表明,负载DOX的MOGN在pH 5.5时DOX释放率为91.92%,在pH 7.4时为12.18%,因此有利于肿瘤环境。纳米凝胶在pH 5.5和6.8时的药物释放遵循Korsmeyer-Peppas模型,在pH 7.4时遵循Higuchi模型。随后,通过使用细胞的细胞毒性研究,还研究了在肿瘤部位的有效DOX释放。因此,合成的纳米凝胶具有高载药量以及在模拟肿瘤环境中优异的pH触发崩解和DOX释放性能,可能是一种用于抗癌药物靶向和控释的有前景的候选药物递送系统。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06fb/9658875/c541bc1a2a1d/polymers-14-04697-sch001.jpg

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