Glucose transporter and folic acid receptor-mediated Pluronic P105 polymeric micelles loaded with doxorubicin for brain tumor treating

Abstract

In this study, glucose transporter and folic acid (FA) receptor-mediated Pluronic P105 polymeric micelles loaded with DOX (GF-DOX) were prepared for enhancing the blood-brain barrier (BBB) transportation and improving the drug accumulation in the glioma cells. The pH-triggered DOX release of GF-DOX indicating a comparatively fast drug release at weak acidic condition and stable state of the carrier at physiological environment. The transport of GF-DOX across the in vitro BBB model showed that GF-DOX exhibited higher BBB transportation ability with the transporting ratio of 21.47% in 4 h. The carrier was internalized into C6 glioma cells upon crossing the BBB model for the combined effect of the brain targeting by transportation of glucose transporter and active tumor cell targeting by FA receptor-mediated endocytosis. Moreover, minimized weight changes and high suppression ratio of tumor growth were observed after intravenous injection of GF-DOX. In conclusion, the glucose transporter and FA dual-targeting micelles would provide a safe and effective strategy for new modalities to treat brain tumor.

Preparation and antitumor evaluation of self-assembling oleanolic acid-loaded Pluronic P105/D-α-tocopheryl polyethylene glycol succinate mixed micelles for non-small-cell lung cancer treatment

“…10 As a pluronic excipient, P105 is a well-known polymeric inhibitor of P-gp and functions via inhibiting ATPase and fluidizing membrane. 52 cellular uptake assays and in vivo imaging of DiR-loaded micelles. The combined effect of the pluronic block polymer and passively targeted drug-resistant tumors by block copolymers may be the primary reason for the inhibition of tumor growth in the OA-micelles treatment groups.…”

c(RGDyK)-decorated Pluronic micelles for enhanced doxorubicin and paclitaxel delivery to brain glioma

“…[11][12][13] However, their in vivo efficacy and therapeutic mechanism have not been illustrated in detail. To overcome the BBB and blood-brain tumor barrier and deliver drugs to the central nervous system, strategies based on delivery systems that inhibit drug efflux transporters in the BBB have been proposed.…”

The effect of subchronic supplementation with folic acid on homocysteine induced seizures

“…There is evidence that the nervous system response is related both to the dose and the duration of treatment, as well as the folate status of the patient (32). After ingestion, folic acid is reduced by dihydrofolate reductase and then converted to biologically active forms.…”