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Merck
  • Vitamin E TPGS prodrug micelles for hydrophilic drug delivery with neuroprotective effects.

Vitamin E TPGS prodrug micelles for hydrophilic drug delivery with neuroprotective effects.

International journal of pharmaceutics (2012-09-08)
Yu Mi, Jing Zhao, Si-Shen Feng
摘要

Double emulsion has been used most often in formulation of hydrophilic drugs by nanoparticles of biodegradable polymers, which has disadvantages such as low drug loading and low drug encapsulation efficiency due to the drug loss in the process. The drug release may be too fast for sustained chemotherapy. We developed in this research a D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) prodrug micelle system with cisplatin as a model hydrophilic drug. We demonstrated that such a system can successfully deliver the model hydrophilic drug with a low critical micelle concentration (CMC) of only 5.01 mg/L, a high drug load of 4.95% (w/w) and a pH-responsive drug release kinetics and higher cellular uptake in comparison with the original drug and the TPGS-cisplatin prodrug itself. The cell viability experiment showed great enhancement of the cisplatin chemotherapy, which is demonstrated by the IC50 value reduced from 3.95, 0.98, 0.19 for cisplatin to 1.36, 0.51, 0.08 μg/mL for the TPGS prodrug micelle formulation after 24, 48, 72 h culture with the HepG2 hepatocarcinoma cells, respectively. Furthermore, such a TPGS prodrug micellar formulation showed significant neuroprotective effects for the cisplatin chemotherapy, which is demonstrated by the greatly increased IC50 value for the SH-SY5Y neuroblast-like cells in comparison between cisplatin and the TPGS prodrug micelle formulation. The TPGS prodrug micelles can also be generalized to become a new strategy for codelivery of hydrophilic and hydrophobic drugs and/or imaging agents.

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Sigma-Aldrich
D-α-维生素E聚乙二醇琥珀酸酯, BioXtra, water soluble vitamin E conjugate
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