Hydrophobically Modified Keratin Vesicles for GSH-Responsive Intracellular Drug Release.
Redox-responsive polymersomes were prepared by self-assembly of a hydrophobically modified keratin and employing a water addition/solvent evaporation method. Polyethylene glycol-40 stearate (PEG40ST) was chosen as hydrophobic block to be coupled to keratin via radical grafting. The amphiphilic polymer exhibited low critical aggregation concentration (CAC; 10 μg/mL), indicating a good thermodynamic stability. The polymeric vesicles loaded both hydrophilic methotrexate and hydrophobic curcumin with high entrapment efficiencies, and showed a GSH-dependent drug release rate. Confocal studies on HeLa cells revealed that the obtained polymersomes were efficiently internalized. Biocompatibility properties of the proposed delivery vehicle were assessed in HET-CAM test and Balb-3T3 mouse fibroblasts. Polymersomes loaded with either methotrexate or curcumin inhibited HeLa and CHO-K1 cancer cells proliferation. Overall, the proposed keratin polymersomes could be efficient nanocarriers for chemotherapeutic agents.
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria , 87036 Rende (CS), Italy.
Manuela
M
Curcio
Universidad de Santiago de Compostela , Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, 15782 Santiago de Compostela, Spain.
Barbara
B
Blanco-Fernandez
Universidad de Santiago de Compostela , Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, 15782 Santiago de Compostela, Spain.
Luis
L
Diaz-Gomez
Universidad de Santiago de Compostela , Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, 15782 Santiago de Compostela, Spain.
Angel
A
Concheiro
Universidad de Santiago de Compostela , Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, 15782 Santiago de Compostela, Spain.
Carmen
C
Alvarez-Lorenzo
D016475:3T3 Cells; D000818:Animals; D001692:Biological Transport; D016466:CHO Cells; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D065546:Drug Liberation; D004355:Drug Stability; D005978:Glutathione / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D006367:HeLa Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D042541:Intracellular Space / Q000378:metabolism*; D007633:Keratins / Q000737:chemistry*; D051379:Mice; D013816:Thermodynamics
D004337:Drug Carriers; D007633:Keratins; D005978:Glutathione