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Preparation and Evaluation of Long-Circulating Deoxypodophyllotoxin-Loaded Liposomes Using Poly(Ethylene Glycol)-Distearoylphosphatidylethanolamine

Journal of Pharmaceutical Innovation, ISSN: 1939-8042, Vol: 11, Issue: 2, Page: 134-142
2016
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Article Description

Purpose: Deoxypodophyllotoxin (DPT) is a new potential anti-tumor drug with nearly no water solubility and low permeability. Hence, we prepared a poly (ethylene glycol)-distearoylphosphatidylethanolamine (PEG-DSPE) modified long-circulation liposomes for enhanced solubility and anti-tumor capacity of DPT with clinical expectation. Method and Result: DPT-loaded long-circulation liposomes (DPT-LCLPs) were prepared by thin-film dispersion method, and characteristics including particle size, zeta potential and entrapment efficiency of re-dissolution after lyophilization were 110.5 ± 4.5 nm, −15.06 ± 1.14 mV, and 92.45 ± 5.21 %, respectively. TEM images showed that DPT-LCLPs appeared as spherical or ellipsoidal in shape with multilayer membrane. Moreover, sensitive liquid chromatography method was developed for quantification of DPT concentration in rat plasma with diazepam as internal standard (IS), and the results revealed that two-compartment intravenous model analysis was better with respect to data fitted by Kinetica 4.4 program. The terminal phase half-life (T) of DPT-LCLPs group was estimated to be approximately 155 min; AUC was more than three times higher than that of control group, demonstrating a prolonged circulation time due to PEG modification. In vivo investigation on Heps tumor-xenografted mice, DPT-LCLPs group indicated higher anti-tumor efficacy with dose-dependence, comparing to Etoposide and control group. Conclusion: PEG-modified liposomes highly improved the solubility and blood circulation of DPT with simple preparation for potentially enhanced anti-cancer therapy.

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