van Straten Demian, Bimbo Jaime Fernández, Hennink Wim E, Vermonden Tina, Schiffelers Raymond M
CDL Research, University Medical Center Utrecht, 3584CX Utrecht, The Netherlands.
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584CG Utrecht, The Netherlands.
Pharmaceutics. 2025 Jan 17;17(1):127. doi: 10.3390/pharmaceutics17010127.
BACKGROUND/OBJECTIVES: Glioblastoma is the most common and lethal primary brain tumor. Patients often suffer from tumor- and treatment induced vasogenic edema, with devastating neurological consequences. Intracranial edema is effectively treated with dexamethasone. However, systemic dexamethasone requires large doses to surpass the blood brain barrier in therapeutic quantities, which is associated with significant side effects. The aim of this study was to investigate a biodegradable, dextran-hydroxyethyl methacrylate (dex-HEMA) based hydrogel, containing polymeric micelles loaded with dexamethasone and liposomes encapsulating dexamethasone phosphate for localized and prolonged delivery.
Poly(ethylene glycol)--poly(-2-benzoyloxypropyl methacrylamide (mPEG--p(HPMA-Bz)) micelles were loaded with dexamethasone and characterized. The dexamethasone micelles, together with dexamethasone phosphate liposomes, were dispersed in an aqueous dex-HEMA solution followed by radical polymerization using a photoinitiator in combination with light. The kinetics and mechanisms of drug release from this hydrogel were determined.
The diameter of the nanoparticles was larger than the mesh size of the hydrogel, rendering them immobilized in the polymer network. The micelles immediately released free dexamethasone from the hydrogel for two weeks. The dexamethasone phosphate loaded in the liposomes was not released until the gel degraded and intact liposomes were released, starting after 15 days. The different modes of release result in a biphasic and sequential release profile of dexamethasone followed by dexamethasone phosphate liposomes.
The results show that this hydrogel system loaded with both dexamethasone polymeric micelles and dexamethasone phosphate loaded liposomes has potential as a local delivery platform for the sequential release of dexamethasone and dexamethasone phosphate, for the intracranial treatment of glioblastoma associated edema.
背景/目的：胶质母细胞瘤是最常见且致命的原发性脑肿瘤。患者常因肿瘤及治疗引发血管源性水肿，导致严重的神经后果。地塞米松可有效治疗颅内水肿。然而，全身性地塞米松需要大剂量才能以治疗量越过血脑屏障，这会带来显著的副作用。本研究的目的是研究一种可生物降解的、基于葡聚糖 - 甲基丙烯酸羟乙酯（dex - HEMA）的水凝胶，其含有负载地塞米松的聚合物胶束和包裹地塞米松磷酸酯的脂质体，用于局部和延长释放。
将聚乙二醇 - 聚（ - 2 - 苯甲酰氧基丙基甲基丙烯酰胺）（mPEG - p(HPMA - Bz)）胶束负载地塞米松并进行表征。将地塞米松胶束与地塞米松磷酸酯脂质体分散在水性dex - HEMA溶液中，然后使用光引发剂结合光进行自由基聚合。测定了该水凝胶中药物释放的动力学和机制。
纳米颗粒的直径大于水凝胶的网孔尺寸，使其固定在聚合物网络中。胶束在两周内立即从水凝胶中释放出游离地塞米松。脂质体中负载的地塞米松磷酸酯直到凝胶降解且完整的脂质体释放出来才开始释放，这在15天后开始。不同的释放模式导致地塞米松先呈双相和顺序释放，随后是地塞米松磷酸酯脂质体。
结果表明，这种同时负载地塞米松聚合物胶束和地塞米松磷酸酯负载脂质体的水凝胶系统有潜力作为局部给药平台，用于顺序释放地塞米松和地塞米松磷酸酯，用于颅内治疗胶质母细胞瘤相关水肿。
