Design of Biopolymer-Based Interstitial Therapies for the Treatment of Glioblastoma.
Design of Biopolymer-Based Interstitial Therapies for the Treatment of Glioblastoma.
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DOI：
10.3390/ijms222313160
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发表时间：
2021-12-06
影响因子：
5.6
通讯作者：
Ainslie KM
中科院分区：
文献类型：
--
作者：
Pena ES;Graham-Gurysh EG;Bachelder EM;Ainslie KM
多形性胶质母细胞瘤 (GBM) 是最常见的原发性脑癌，发病率最高，目前的治疗方法导致 5 年生存率仅为 5.6%。间质治疗是提高生存率的一种选择。间质疗法的药物输送最常使用封装药物的聚合物植入物，该药物随着聚合物降解而释放。间质疗法作为 GBM 的一种治疗选择已被广泛研究，因为它比全身化疗具有多种优势。首先，它可以应用于血脑屏障后面，增加可以使用的可能的化疗候选药物的数量，并降低治疗的全身水平，同时将其集中在癌症源附近。通过间质治疗，随着植入物聚合物的降解，多种药物可以局部释放到切除部位的大脑中，并且可以定制这些药物的释放曲线以优化联合治疗或维持协同比例。这可以绕过血脑屏障，减轻全身毒性，并解决肿瘤的耐药性。然而，定制药物释放需要适当考虑药物、聚合物和配制方法之间的复杂关系。药物的理化性质可导致与聚合物基质的分子间键合，并影响植入物中的药物分布，具体取决于所使用的配制方法。本综述重点关注目前针对 GBM 应用间质疗法的工作，讨论聚合物和配方方法，并为未来植入式生物可降解材料提供设计考虑。
Glioblastoma multiforme (GBM) is the most common form of primary brain cancer and has the highest morbidity rate and current treatments result in a bleak 5-year survival rate of 5.6%. Interstitial therapy is one option to increase survival. Drug delivery by interstitial therapy most commonly makes use of a polymer implant encapsulating a drug which releases as the polymer degrades. Interstitial therapy has been extensively studied as a treatment option for GBM as it provides several advantages over systemic administration of chemotherapeutics. Primarily, it can be applied behind the blood–brain barrier, increasing the number of possible chemotherapeutic candidates that can be used and reducing systemic levels of the therapy while concentrating it near the cancer source. With interstitial therapy, multiple drugs can be released locally into the brain at the site of resection as the polymer of the implant degrades, and the release profile of these drugs can be tailored to optimize combination therapy or maintain synergistic ratios. This can bypass the blood–brain barrier, alleviate systemic toxicity, and resolve drug resistance in the tumor. However, tailoring drug release requires appropriate consideration of the complex relationship between the drug, polymer, and formulation method. Drug physicochemical properties can result in intermolecular bonding with the polymeric matrix and affect drug distribution in the implant depending on the formulation method used. This review is focused on current works that have applied interstitial therapy towards GBM, discusses polymer and formulation methods, and provides design considerations for future implantable biodegradable materials.
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