Efficient Chemotherapy of Rat Glioblastoma Using Doxorubicin-Loaded PLGA Nanoparticles with Different Stabilizers

Abstract

BackgroundChemotherapy of glioblastoma is largely ineffective as the blood-brain barrier (BBB) prevents entry of most anticancer agents into the brain. For an efficient treatment of glioblastomas it is necessary to deliver anti-cancer drugs across the intact BBB. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles coated with poloxamer 188 hold great promise as drug carriers for brain delivery after their intravenous injection. In the present study the anti-tumour efficacy of the surfactant-coated doxorubicin-loaded PLGA nanoparticles against rat glioblastoma 101/8 was investigated using histological and immunohistochemical methods.MethodologyThe particles were prepared by a high-pressure solvent evaporation technique using 1% polyvinylalcohol (PLGA/PVA) or human serum albumin (PLGA/HSA) as stabilizers. Additionally, lecithin-containing PLGA/HSA particles (Dox-Lecithin-PLGA/HSA) were prepared. For evaluation of the antitumour efficacy the glioblastoma-bearing rats were treated intravenously with the doxorubicin-loaded nanoparticles coated with poloxamer 188 using the following treatment regimen: 3×2.5 mg/kg on day 2, 5 and 8 after tumour implantation; doxorubicin and poloxamer 188 solutions were used as controls. On day 18, the rats were sacrificed and the antitumour effect was determined by measurement of tumour size, necrotic areas, proliferation index, and expression of GFAP and VEGF as well as Isolectin B4, a marker for the vessel density.ConclusionThe results reveal a considerable anti-tumour effect of the doxorubicin-loaded nanoparticles. The overall best results were observed for Dox-Lecithin-PLGA/HSA. These data demonstrate that the poloxamer 188-coated PLGA nanoparticles enable delivery of doxorubicin across the blood-brain barrier in the therapeutically effective concentrations.

Codelivery of doxorubicin and curcumin with lipid nanoparticles results in improved efficacy of chemotherapy in liver cancer

“…35 Similarly, we also observed high EE of DOX (90%), which might be related to the conversion of DOX hydrochloride into a less soluble free base to facilitate DOX distribution into the oil phase. 36 A slightly improved EE of DOX with the increase of Cur was detected, indicating a promoting effect of Cur on the encapsulation of DOX. This result verified the hypothesis in terms of the zeta potential measurement.…”

Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy

“…anti-tumor efficacy in a glioblastoma rat model [453]. The modifications proposed by these authors were the stabilization by polyvinylalcohol (PVA) and human serum albumin (HAS), and the inclusion of lecithin in the core of the PLGA/HSA formulations that stabilize the coating of poloxamer 188 due to the affinity between both components.…”

“…The modifications proposed by these authors were the stabilization by polyvinylalcohol (PVA) and human serum albumin (HAS), and the inclusion of lecithin in the core of the PLGA/HSA formulations that stabilize the coating of poloxamer 188 due to the affinity between both components. Studies on a rat glioblastoma model demonstrated the enhanced anti-tumor effect of the doxorubicin-loaded lecithincontaining PLGA/HSA formulation coated with poloxamer 188, the key ingredient for the delivery of the drug to the brain [453].…”

Preparation and characterization of Tamoxifen citrate loaded nanoparticles for breast cancer therapy

“…3,6 Different anticancer drugs, including Tamoxifen citrate, were loaded in the PLGA nanoparticles by many researchers. [7][8][9][10] Tamoxifen citrate, an antiestrogenic compound, is the first choice for hormonal treatment of breast cancer in both post and premenopausal women for the last few decades. It is often used as an adjuvant therapy following primary treatment of early stage breast cancer.…”