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Doxorubicin liposomes as an investigative model to study the skin permeation of nanocarriers.

International journal of pharmaceutics (2015-04-26)
Cedar H A Boakye, Ketan Patel, Mandip Singh
ABSTRACT

The objectives of this study were to develop an innovative investigative model using doxorubicin as a fluorophore to evaluate the skin permeation of nanocarriers and the impact of size and surface characteristics on their permeability. Different doxorubicin-loaded liposomes with mean particle size <130 nm and different surface chemistry were prepared by ammonium acetate gradient method using DPPC, DOPE, Cholesterol, DSPE-PEG 2000 and 1,1-Di-((Z)-octadec-9-en-1-yl) pyrrolidin-1-ium chloride (CY5)/DOTAP/1,2-dioleoyl-sn-glycero-3-phosphate (DOPA) as the charge modifier. There was minimal release of doxorubicin from the liposomes up to 8h; indicating that fluorescence observed within the skin layers was due to the intact liposomes. Liposomes with particle sizes >600 nm were restricted within the stratum corneum. DOTAP (p<0.01) and CY5 (p<0.05) liposomes demonstrated significant permeation into the skin than DOPA and PEG liposomes. Tape stripping significantly (p<0.01) enhanced the skin permeation of doxorubicin liposomes but TAT-decorated doxorubicin liposomes permeated better (p<0.005). Blockage of the hair follicles resulted in significant reduction in the extent and intensity of fluorescence observed within the skin layers. Overall, doxorubicin liposomes proved to be an ideal fluorophore-based model. The hair follicles were the major route utilized by the liposomes to permeate skin. Surface charge and particle size played vital roles in the extent of permeation.

MATERIALS
Product Number
Brand
Product Description

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Ethanol Fixative 80% v/v, suitable for fixing solution (blood films)
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Cholesterol, from sheep wool, ≥92.5% (GC), powder
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Ethanol standards 10% (v/v), 10 % (v/v) in H2O, analytical standard
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1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine, ≥99.0% (10 mg phospholipid per ml CHCl3, TLC)
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