Intracranial In Situ Thermosensitive Hydrogel Delivery of Temozolomide Accomplished by PLGA-PEG-PLGA Triblock Copolymer Blending for GBM Treatment.
Intracranial In Situ Thermosensitive Hydrogel Delivery of Temozolomide Accomplished by PLGA-PEG-PLGA Triblock Copolymer Blending for GBM Treatment.
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通过 PLGA-PEG-PLGA 三嵌段共聚物共混实现替莫唑胺的颅内原位热敏水凝胶递送，用于 GBM 治疗。
作者：
胶质母细胞瘤（GBM）手术切除后复发已成为一个巨大的障碍，以克服。在这项研究中，可生物降解的热敏三嵌段共聚物，聚（D，L-乳酸-羟基乙酸）-b-聚（乙二醇）-b-聚（D，L-乳酸-羟基乙酸）（PLGA-PEG-PLGA）作为药物递送系统，负载微粉化替莫唑胺（micro-TMZ），在切除腔内形成原位药物凝胶贮库。流变学研究揭示了水凝胶在各种条件下的粘弹性特征。为了检查影响凝胶化温度的分子特征，利用1H-NMR、反向门控去偶13 C-NMR和GPC。Cryo-SEM和XRD旨在揭示水凝胶的外观和微TMZ的存在状态。我们研究了如何混合聚合物来改变凝胶点（Tgel）并使用线性回归拟合Tgel与其他因变量之间的相关性。为了模拟水凝胶在脑脊液中的溶解，使用了无膜溶解方法。在体外，micro-TMZ@PLGA-PEG-PLGA水凝胶表现出Korsmeyer-Peppas和零级释放动力学响应于不同的药物负载，并且在体内，它以惊人的高速率抑制GBM复发。Micro-TMZ@PLGA-PEG-PLGA显示出比腹膜内TMZ注射更安全和更有效的化疗形式，导致显著的存活率（40%，n = 10），远远高于腹膜内TMZ注射（22%，n = 9）。通过证明micro-TMZ@PLGA-PEG-PLGA水凝胶的可行性和有效性，我们的研究建立了一种治疗GBM复发的新型化疗策略。
Glioblastoma (GBM) recurrence after surgical excision has grown to be a formidable obstacle to conquer. In this research, biodegradable thermosensitive triblock copolymer, poly(D, L–lactic acid–co–glycolic acid)–b–poly(ethylene glycol)–b–poly(D, L–lactic acid–co–glycolic acid (PLGA–PEG–PLGA) was utilized as the drug delivery system, loading with micronized temozolomide(micro-TMZ) to form an in situ drug–gel depot inside the resection cavity. The rheology studies revealed the viscoelastic profile of hydrogel under various conditions. To examine the molecular characteristics that affect gelation temperature, 1H–NMR, inverse gated decoupling 13C–NMR, and GPC were utilized. Cryo-SEM and XRD were intended to disclose the appearance of the hydrogel and the micro-TMZ existence state. We worked out how to blend polymers to modify the gelation point (Tgel) and fit the correlation between Tgel and other dependent variables using linear regression. To simulate hydrogel dissolution in cerebrospinal fluid, a membraneless dissolution approach was used. In vitro, micro-TMZ@PLGA–PEG–PLGA hydrogel exhibited Korsmeyer–Peppas and zero–order release kinetics in response to varying drug loading, and in vivo, it suppressed GBM recurrence at an astoundingly high rate. Micro-TMZ@PLGA–PEG–PLGA demonstrates a safer and more effective form of chemotherapy than intraperitoneal TMZ injection, resulting in a spectacular survival rate (40%, n = 10) that is much more than intraperitoneal TMZ injection (22%, n = 9). By proving the viability and efficacy of micro-TMZ@PLGA–PEG–PLGA hydrogel, our research established a novel chemotherapeutic strategy for treating GBM recurrence.
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影响因子：
2.2
作者：
Giraudeau, P;Baguet, E
通讯作者：
Baguet, E
DOI：
10.1016/j.nano.2020.102319
发表时间：
2021-01-01
影响因子：
5.4
作者：
Afzalipour, Reza;Khoei, Samideh;Karimi, Mohammad Yahya
通讯作者：
Karimi, Mohammad Yahya
温敏多肽融合干扰素和替莫唑胺的时空组合用于胶质母细胞瘤术后免疫化疗
影响因子：
14
作者：
Liang, Ping;Wang, Guihuai;Gao, Weiping
通讯作者：
Gao, Weiping
影响因子：
6
作者：
Lin W;Xu T;Wang Z;Chen J
通讯作者：
Chen J
影响因子：
2.9
作者：
Liu, Peng;Wang, Bochu;Li, Jun
通讯作者：
Li, Jun