Development of Novel Cytotoxic and Antiangiogenic Nanoformulations for Targeting Malignant Glioma

Abstract

Glioblastoma multiforme or grade IV glioma is defined as the deadliest form of brain tumor, with limited treatment options. The current treatment modalities possess their own pros and cons and lack sensitivity. Hence, there is an urge to find an alternative treatment strategy to tackle glioma that is cost-effective and renders minimum side effects on the normal neuronal cells. One of the prominent characteristics of cancer cells is their acidic pH and hence, the current study is aimed to synthesize pHsensitive liposomal carriers, which could efficiently target U87MG cells at acidic pH. D-limonene and carmustine were loaded into the liposomal carrier and subjected to several physicochemical characterizations to understand its morphology, size, shape, physical stability, and drug release pattern. The results of the study state that blank and drug-loaded liposomes were monodispersed and spherical in shape. The particle size measured using High-Resolution Transmission Electron Microscopy (HR-TEM) shows the size of blank liposomes to be 20 nm, limonene-loaded liposomes to be 84 nm, and carmustine-loaded liposomes to be 53 nm. The drug entrapment study revealed that at the least concentration of the drug tested, i.e., 2 mg, there was maximum Entrapment Efficiency (EE) and Drug Loading Capacity (DLC). For limonene-loaded liposomes, the EE was 44.3 ± 6.58% and DLC was 8.87 ± 2.90, and for carmustine-loaded liposomes, EE was 48.48 ± 7.03% and DLC was 9.69 ± 1.06%. The average size of blank liposomes was 128 ± 5.90 nm with a PDI of 0.235, and zeta potential of -47.7 mV, while D-limonene loaded liposomes had a particle size of 165 ± 8.48 nm with a PDI of 0.271 and zeta potential of +45.6 mV. The size of carmustine-loaded liposomes was found to be 202± 10.01 nm with a PDI of 0.369 and the zeta potential was found to be -45.2 mV. The drug release from limonene-loaded liposomes decreases at varying pH; 6.8 (87.23 ± 8.60%) gt5.5 (86.85 ± 8.60%) gt4.5 (86.62 ± 8.20%) gt7.4 (27.89 ± 4.32). In the case of carmustine-loaded liposomes,