Intracranial In Situ Thermosensitive Hydrogel Delivery of Temozolomide Accomplished by PLGA–PEG–PLGA Triblock Copolymer Blending for GBM Treatment

Abstract

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.