Modified PAMAM Dendrimer-Based Carboplatin Delivery in Glioblastoma: <i>In Vitro</i> and <i>In Vivo</i> Studies

The complex neoplasm of central nervous system malignancies, glioblastoma multiforme (GBM), is often challenging to manage due to its location complexity and anatomical barriers. The majority of conventional anticancer drugs are restricted by the blood-brain barrier, except Temozolomide, which also hampers patients' quality of life. Therefore, a potential carrier system is needed to enhance drug delivery efficiency. In this study, we have prepared the nanoformulation G4PFCP, a G4 PAMAM_OH dendrimer functionalized with folic acid and conjugated with carboplatin, to evaluate its efficacy in drug delivery to the GBM tumor microenvironment. Both the drug loaded (G4PFCP) and drug free (G4PF) nanoparticles have been characterized by spectroscopic and microscopic techniques. They have exhibited properties that are consistent with pH-specific sustained drug release. Both <i>in vivo</i> and <i>in vitro</i> studies have been performed. G4PFCP exhibited enhanced therapeutic efficacy compared to free carboplatin and G4PF in LN18 and LN229 GBM cell lines, which has been evaluated based on induced nuclear fragmentation and chromatin condensation. Furthermore, treatment with G4PFCP led to significant modulation of apoptotic markers, including Cleaved Caspase-9, XIAP, Bax, and DSB protein γ-H2AX. In the rat model, G4PFCP treatment resulted in substantial tumor size reduction and notable antiproliferative and antiangiogenic effects without showing any organ toxicity. The findings suggest that the G4PFCP nanoformulation represents a promising and effective drug delivery system for targeting GBM malignancies.