PURPOSE: To investigate the self-assembly of polyethylene glycol (PEG)-phosphatidylethanolamine (PE) conjugate with water-soluble drugs (doxorubicin hydrochloride, vinorelbine tartrate and vincristine sulfate) and give insight into the mechanism of formation and mode of interaction of the drug with PEG-PE as well as the general principles of self-assembly using pegylated lipid micelles. METHODS: One-step self-assembly method to prepare drug-loaded micelles was developed. The micelles were characterized by dynamic light scattering, transmission electron microscopy, encapsulation efficiency, and release study. NMR was used to study molecular assembly of PEG-PE with doxorubicin. RESULTS: Doxorubicin hydrochloride and vinorelbine tartrate were entrapped into micelles with high efficiency of >99.0% at molar ratios of 1:1 and 2:1 of PEG-PE to drugs, respectively. Drug loading did not measurably perturb either the geometry or the size. It was found that electrostatic interaction and hydrophobic forces are responsible for the intercalation of drugs into PEG-PE micelles. NMR data revealed that the anthracycline ring of doxorubicin was inserted between PE phospholipids, and its amino sugar located in the outer shell of micelle between PEG chains. CONCLUSION: Based on our results, the structure and self-assembly mechanism of water-soluble drugs encapsulated in PEG-PE micelles were proposed.
PURPOSE: To investigate the self-assembly of polyethylene glycol (PEG)-phosphatidylethanolamine (PE) conjugate with water-soluble drugs (doxorubicin hydrochloride, vinorelbine tartrate and vincristine sulfate) and give insight into the mechanism of formation and mode of interaction of the drug with PEG-PE as well as the general principles of self-assembly using pegylated lipid micelles. METHODS: One-step self-assembly method to prepare drug-loaded micelles was developed. The micelles were characterized by dynamic light scattering, transmission electron microscopy, encapsulation efficiency, and release study. NMR was used to study molecular assembly of PEG-PE with doxorubicin. RESULTS:Doxorubicin hydrochloride and vinorelbine tartrate were entrapped into micelles with high efficiency of >99.0% at molar ratios of 1:1 and 2:1 of PEG-PE to drugs, respectively. Drug loading did not measurably perturb either the geometry or the size. It was found that electrostatic interaction and hydrophobic forces are responsible for the intercalation of drugs into PEG-PE micelles. NMR data revealed that the anthracycline ring of doxorubicin was inserted between PEphospholipids, and its amino sugar located in the outer shell of micelle between PEG chains. CONCLUSION: Based on our results, the structure and self-assembly mechanism of water-soluble drugs encapsulated in PEG-PE micelles were proposed.
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