Temozolomide-Loaded Solid Lipid Nanoparticles@Hydrogel for Local Treatment of Tumour

Abstract

Temozolomide (TMZ) is a significant anticancer agent especially for chemotherapy of glioblastoma. In order to reduce the recurrence rate of cancer, in this work an injectable hydrogel composed of TMZ-loaded solid lipid nanoparticles (SLNs) was designed for filling the cavity of a glioblastoma operation. First, TMZ-loaded SLNs (T-SLNs) were prepared by emulsion solvent diffusion and evaporation technology. The optimised formulation showed a particle size of 190.8±15.3nm, a Zeta potential of −20.2±1.7mV, an entrapment efficiency (EE%) of 99.3±0.5%, and drug loading (DL%) of 15.1±2.7%. The optimised formulation was freeze-dried and characterised by scanning electron microscopy (SEM), differential thermogravimetry (DTG), X-ray diffraction (XRD), and stability tests. The freeze-dried T-SLNs were then incorporated into a hydroxypropyl chitosan (HPCS)/diarylaldehyde PEG (PEG-DF) hydrogel bonded with an MRI contrast agent. The hydrogels were evaluated for invitro drug release and cytotoxicity. The results indicated that compared with free TMZ, the T-SLNs@hydrogel prolonged drug release, and both blank SLNs and hydrogel materials did not exhibit cytotoxicity, suggesting the therapeutic efficacy of TMZ was reserved. Thus, comparing with its conventional oral administration, the obtained TMZ-loaded SLNs and the hydrogel could be more potent for local treatment of glioblastoma after an operation.