Understanding the Role of Poloxamer 407 based Thermoreversible In Situ Gelling Hydrogel for Delivery of PEGylated Melphalan Conjugate
Understanding the Role of Poloxamer 407 based Thermoreversible In Situ Gelling Hydrogel for Delivery of PEGylated Melphalan Conjugate
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DOI：
10.2174/1567201813666160204114000
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发表时间：
2016-01-01
影响因子：
2.4
通讯作者：
Saraf, Shailendra
中科院分区：
文献类型：
--
作者：
Alexander, Amit;Saraf, Swarnlata;Saraf, Shailendra
背景：水凝胶是一种聚合物网络，可以保持大量的水分。因此，这些输送系统一直是科学家联谊会深入研究的问题。目的：探讨聚乙二醇化抗癌药物在泊洛沙姆热敏注射水凝胶上的作用。方法：首先通过聚乙二醇化马法兰与两种线性甲氧基聚乙二醇(M-PEG)的聚乙二醇化来提高马法兰的溶解度。M-PEG2000和5000 Da形成聚乙二醇化的马法兰偶联物(MLPEG)。在我们之前的研究中，我们发现所制备的偶联物有效地提高了马法兰的溶解度，并显著降低了由于聚乙二醇链的存在而产生的溶血效应。因此，在本工作中，将制备的结合物(MLPEG5000和2000)负载到热敏性泊洛沙姆407(P407)凝胶中，以制备可注射水凝胶(MPX)。结果：MPX-CG水凝胶在2小时内只有43%的药物从MPX-CG水凝胶中被释放，从而使PEO链更加紧密，显著减少了药物从给药系统中的初始爆发。此外，与MPX-7.4凝胶相比，MPX-CG凝胶的扩散系数(D)更低。为确定贮库的形成，将制备的水凝胶通过皮下和肌肉内途径给予Wistar大鼠。结论：基于P407的可注射水凝胶可以在降低宿主细胞毒性的情况下，在低剂量烷化剂的输送方面发挥重要作用。
Background: Hydrogels are the polymeric network, which can retain large amount of water. Thus, these delivery systems always remained an issue of intensive research among the scientist fraternity. Objective: In this piece of work, we have reconnoitered the significance of the PEGylated anticancer loaded drug onto poloxamer based thermoresponsive injectable hydrogel to understand the role of delivery system.Method: To accomplish the objective, firstly it was necessary to improve the solubility of the melphalan, achieved by PEGylation of the drug with two grades of linear methoxy poly ethylene glycol (M-PEG), viz. M-PEG 2000 and 5000 Da to form a PEGylated melphalan conjugate (MLPEG). In our previous study, we have found that the prepared conjugates were efficiently enhanced the solubility of the melphalan and significantly reduced the hemolytic effect due to the presence of the PEG chains. Thus, in the present work, the prepared conjugates (MLPEG 5000 and 2000) were loaded to the thermosensitive Poloxamer 407 (P407) gel to produce an injectable hydrogel (MPX). To underline the reduction of the initial burst of the drug at the site of action, one of the hydrogels was prepared in the presence of the NaCl salt.Results: This in turn, tightened the PEO chains and remarkably reduced the drug's initial burst from the delivery system as only 43 % of drug was released during 2 hours from MPX-CG hydrogel. Moreover, a lower diffusion coefficient (D) was noticed for MPX-CG gel as compared with MPX-7.4 gel. To confirm the depot formation, prepared hydrogels were administered to Wistar rats via subcutaneous and intramuscular routes.Conclusion: Thus, P407 based injectable hydrogel could play an important role for the delivery of a low dose-alkylating agent with reduced host cytotoxicity.