Dataset Information

Pluronic F127 and D-?-Tocopheryl Polyethylene Glycol Succinate (TPGS) Mixed Micelles for Targeting Drug Delivery across The Blood Brain Barrier.

ABSTRACT: A novel polymeric mixed micelle composed of Pluronic F127 and D-?-tocopheryl polyethylene glycol succinate (TPGS) was developed to improve the delivery of fluorescent dyes and protein across the blood brain barrier (BBB). Rhodamine 123 (Rho123) and DiR loaded mixed micelles, composed of Pluronic F127 and TPGS with proportion of 4:1 (FT), were prepared by thin-film hydration, and ?-galactosidase (?-Gal) loaded FT mixed micelles were prepared by self-assembly. The brain-targeted capability of FT mixed micelles were evaluated both in vitro and in vivo. The FT mixed micelles showed that a average particle size of 20.03?nm, and a low CMC of 0.0031% in water. The in vitro release of Rho123 from Rho123 loaded FT mixed micelles (FT/Rho123) presented a sustained-release property. FT/Rho123 also showed higher efficiency for the accumulation in brain capillary endothelial cells (BCECs) and brain tissues. ?-Gal, a model protein, was also delivered and accumulated efficiently in the brain by spontaneous loading in the FT mixed micelles. Therefore, the results indicated that F127/TPGS mixed micelles may be considered as an effective nanocarrier for the brain-targeted delivery of diagnostic and therapeutic drugs.

SUBMITTER: Meng X

PROVIDER: S-EPMC5462762 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Pluronic F127 and D-α-Tocopheryl Polyethylene Glycol Succinate (TPGS) Mixed Micelles for Targeting Drug Delivery across The Blood Brain Barrier.

Meng Xin X Liu Jiansheng J Yu Xiangrong X Li Jiajia J Lu Xiaotong X Shen Teng T

Scientific reports 20170607 1

A novel polymeric mixed micelle composed of Pluronic F127 and D-α-tocopheryl polyethylene glycol succinate (TPGS) was developed to improve the delivery of fluorescent dyes and protein across the blood brain barrier (BBB). Rhodamine 123 (Rho123) and DiR loaded mixed micelles, composed of Pluronic F127 and TPGS with proportion of 4:1 (FT), were prepared by thin-film hydration, and β-galactosidase (β-Gal) loaded FT mixed micelles were prepared by self-assembly. The brain-targeted capability of FT m ...[more]

PMID: 28592843

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Project description:Here, we developed Pluronic® P123/F127 (poloxamer) mixed micelles for the intravenous delivery of the anticancer drug sorafenib (SRB) or its combination with verteporfin (VP), a photosensitizer for photodynamic therapy that should complement well the cytotoxicity profile of the chemotherapeutic. SRB loading inside the core of micelles was governed by the drug:poloxamer weight ratio, while in the case of the SRB-VP combination, a mutual interference between the two drugs occurred and only specific ratios could ensure maximum loading efficiency. Coentrapment of SRB did not alter the photophysical properties of VP, confirming that SRB did not participate in any bimolecular process with the photosensitizer. Fluorescence resonance energy-transfer measurement of micelles in serum protein-containing cell-culture medium demonstrated the excellent stability of the system in physiologically relevant conditions. These results were in line with the results of the release study showing a release rate of both drugs in the presence of proteins slower than in phosphate buffer. SRB release was sustained, while VP remained substantially entrapped in the micelle core. Cytotoxicity studies in MDA-MB231 cells revealed that at 24 hours, SRB-loaded micelles were more active than free SRB only at very low SRB concentrations, while at 24+24 hours a prolonged cytotoxic effect of SRB-loaded micelles was observed, very likely mediated by the block in the S phase of the cell cycle. The combination of SRB with VP under light exposure was less cytotoxic than both the free combination and VP-loaded micelles + SRB-loaded micelles combination. This behavior was clearly explainable in terms of micelle uptake and intracellular localization. Besides the clear advantage of delivering SRB in poloxamer micelles, our results provide a clear example that each photochemotherapeutic combination needs detailed investigations on their particular interaction, and no generalization on enhanced cytotoxic effects should be derived a priori.

Project description:Background:Multidrug resistance (MDR) is the major reason for the failure of chemotherapy in colon cancer. Bufalin (BU) is one of the most effective antitumor active constituents in Chansu. Our previous study found that BU can effectively reverse P-glycoprotein (P-gp)-mediated MDR in colon cancer. However, the clinical application of BU is limited due to its low solubility in water and high toxicity. In the present study, a multifunctional delivery system based on vitamin-E- succinate grafted chitosan oligosaccharide (VES-CSO) and cyclic (arginine-glycine-aspartic acid peptide) (RGD)-modified d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) was prepared by emulsion solvent evaporation method for targeted delivery of BU to improve the efficacy of drug-resistant colon cancer therapy. Methods:The cytotoxicity of BU-loaded micelles against drug-resistant colon cancer LoVo/ADR and HCT116/LOHP cells was measured by CCK-8 assay. The cellular uptake, Rho123 accumulation, and cell apoptosis were determined by flow cytometry. The expression of apoptosis-related protein and P-gp was measured by Western blot assay. The antitumor activity of BU-loaded micelles was evaluated in LoVo/ADR-bearing nude mice. Results:BU-loaded VES-CSO/TPGS-RGD mixed micelles (BU@VeC/T-RGD MM) were 140.3 nm in diameter with zeta potential of 8.66 mV. The BU@VeC/T-RGD MM exhibited good stability, sustained-release pattern, higher intracellular uptake, and greater cytotoxicity in LoVo/ADR cells. Furthermore, the mechanisms of the BU@VeC/T-RGD MM to overcome MDR might be due to enhanced apoptosis rate and P-gp efflux inhibition. Subsequently, in vivo studies confirmed an enhanced therapeutic efficiency and reduced side effects associated with BU@VeC/T-RGD MM compared with free BU, owing to the enhanced permeation and retention effect, improved pharmacokinetic behavior, and tumor targeting, which lead to MDR-inhibiting effect in LoVo/ADR-bearing nude mice. Conclusion:Our results demonstrated that VeC/T-RGD MM could be developed as a potential delivery system for BU to improve its antitumor activity against drug-resistant colon cancer.

Dataset Information

Pluronic F127 and D-?-Tocopheryl Polyethylene Glycol Succinate (TPGS) Mixed Micelles for Targeting Drug Delivery across The Blood Brain Barrier.

Publications

Pluronic F127 and D-α-Tocopheryl Polyethylene Glycol Succinate (TPGS) Mixed Micelles for Targeting Drug Delivery across The Blood Brain Barrier.

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