ABSTRACT
The survival of patients with glioblastoma multiforme (GBM), the most common and invasive form of malignant brain tumors, remains poor despite advances in current treatment methods including surgery, radiotherapy, and chemotherapy. Minocycline is a semi-synthetic tetracycline derivative that has been widely used as an antibiotic and more recently, it has been utilized as an antiangiogenic factor to inhibit tumorigenesis. The objective of this study was to investigate the utilization of electrospraying process to fabricate minocycline-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles with high drug loading and loading efficiency and to evaluate their ability to induce cell toxicity in human glioblastoma (i.e., U87-MG) cells. The results from this study demonstrated that solvent mixture of dicholoromethane (DCM) and methanol is the optimal solvent combination for minocycline and larger amount of methanol (i.e., 70:30) resulted in a higher drug loading. All three solvent ratios of DCM:methanol tested produced microparticles that were both spherical and smooth, all in the micron size range. The electrosprayed microparticles were able to elicit a cytotoxic response in U87-MG glioblastoma cells at a lower concentration of drug compared to the free drug. This work provides proof of concept to the hypothesis that electrosprayed minocycline-loaded PLGA microparticles can be a promising agent for the treatment of GBM and could have potential application for cancer therapies.
ABSTRACT
Glioblastoma multiforme (GBM) is the most prevalent and aggressive form of glioma, with poor prognosis and high mortality rates. As GBM is a highly vascularized cancer, antiangiogenic therapies to halt or minimize the rate of tumor growth are critical to improving treatment. In this review, antiangiogenic therapies, including small-molecule drugs, nucleic acids and proteins and peptides, are discussed. The authors further explore biomaterials that have been utilized to increase the bioavailability and bioactivity of antiangiogenic factors for better antitumor responses in GBM. Finally, the authors summarize the current status of biomaterial-based targeting moieties that target endothelial cells in GBM to more efficiently deliver therapeutics to these cells and avoid off-target cell or organ side effects.
