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基于泊洛沙姆F127和聚(乙二醇)-聚(ε-己内酯)-聚(乙二醇)共聚物的新型热敏复合水凝胶的体外药物释放行为

In vitro drug release behavior from a novel thermosensitive composite hydrogel based on Pluronic f127 and poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) copolymer.

作者信息

Gong Chang Yang, Shi Shuai, Dong Peng Wei, Zheng Xiu Ling, Fu Shao Zhi, Guo Gang, Yang Jing Liang, Wei Yu Quan, Qian Zhi Yong

机构信息

State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, PR China.

出版信息

BMC Biotechnol. 2009 Feb 11;9:8. doi: 10.1186/1472-6750-9-8.

Abstract

BACKGROUND

Most conventional methods for delivering chemotherapeutic agents fail to achieve therapeutic concentrations of drugs, despite reaching toxic systemic levels. Novel controlled drug delivery systems are designed to deliver drugs at predetermined rates for predefined periods at the target organ and overcome the shortcomings of conventional drug formulations therefore could diminish the side effects and improve the life quality of the patients. Thus, a suitable controlled drug delivery system is extremely important for chemotherapy.

RESULTS

A novel biodegradable thermosensitive composite hydrogel, based on poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) and Pluronic F127 copolymer, was successfully prepared in this work, which underwent thermosensitive sol-gel-sol transition. And it was flowing sol at ambient temperature but became non-flowing gel at body temperature. By varying the composition, sol-gel-sol transition and in vitro drug release behavior of the composite hydrogel could be adjusted. Cytotoxicity of the composite hydrogel was conducted by cell viability assay using human HEK293 cells. The 293 cell viability of composite hydrogel copolymers were yet higher than 71.4%, even when the input copolymers were 500 microg per well. Vitamin B12 (VB12), honokiol (HK), and bovine serum albumin (BSA) were used as model drugs to investigate the in vitro release behavior of hydrophilic small molecular drug, hydrophobic small molecular drug, and protein drug from the composite hydrogel respectively. All the above-mentioned drugs in this work could be released slowly from composite hydrogel in an extended period. Chemical composition of composite hydrogel, initial drug loading, and hydrogel concentration substantially affected the drug release behavior. The higher Pluronic F127 content, lower initial drug loading amount, or lower hydrogel concentration resulted in higher cumulative release rate.

CONCLUSION

The results showed that composite hydrogel prepared in this paper were biocompatible with low cell cytotoxicity, and the drugs in this work could be released slowly from composite hydrogel in an extended period, which suggested that the composite hydrogel might have great potential applications in biomedical fields.

摘要

背景

尽管达到了毒性全身水平,但大多数传统的化疗药物递送方法都无法达到治疗浓度。新型控释药物递送系统旨在以预定速率在预定时间段内将药物递送至靶器官,克服了传统药物制剂的缺点,因此可以减少副作用并提高患者的生活质量。因此,合适的控释药物递送系统对于化疗极为重要。

结果

在本研究中成功制备了一种基于聚(乙二醇)-聚(ε-己内酯)-聚(乙二醇)(PEG-PCL-PEG,PECE)和普朗尼克F127共聚物的新型可生物降解热敏复合水凝胶,其经历了热敏性溶胶-凝胶-溶胶转变。它在环境温度下为流动溶胶,但在体温下变为非流动凝胶。通过改变组成,可以调节复合水凝胶的溶胶-凝胶-溶胶转变和体外药物释放行为。使用人HEK293细胞通过细胞活力测定来进行复合水凝胶的细胞毒性实验。即使每孔输入共聚物为500微克,复合水凝胶共聚物的293细胞活力仍高于71.4%。分别使用维生素B12(VB12)、厚朴酚(HK)和牛血清白蛋白(BSA)作为模型药物,研究亲水性小分子药物、疏水性小分子药物和蛋白质药物从复合水凝胶中的体外释放行为。本研究中的所有上述药物都可以在较长时间内从复合水凝胶中缓慢释放。复合水凝胶的化学成分、初始载药量和水凝胶浓度对药物释放行为有显著影响。普朗尼克F127含量越高、初始载药量越低或水凝胶浓度越低,累积释放率越高。

结论

结果表明,本文制备的复合水凝胶具有生物相容性且细胞毒性低,本研究中的药物可以在较长时间内从复合水凝胶中缓慢释放,这表明复合水凝胶在生物医学领域可能具有巨大的潜在应用价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0228/2654890/d7fcaefe2b08/1472-6750-9-8-1.jpg

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