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AAPS PharmSciTech

, 20:99 | Cite as

Co-delivery of Doxorubicin and Ceramide in a Liposomal Formulation Enhances Cytotoxicity in Murine B16BL6 Melanoma Cell Lines

  • Li Chen
  • Hamad Alrbyawi
  • Ishwor Poudel
  • Robert D. Arnold
  • R. Jayachandra BabuEmail author
Research Article Theme: Translational Multi-Disciplinary Approach for the Drug and Gene Delivery Systems
  • 186 Downloads
Part of the following topical collections:
  1. Theme: Translational Multi-Disciplinary Approach for the Drug and Gene Delivery Systems

Abstract

This study reports co-delivery of doxorubicin (DOX) and ceramide in a liposomal system in B16BL6 melanoma cell lines for enhanced cytotoxic effects. Different types of ceramides (C6-ceramide, C8-ceramide, and C8-glucosylceramide) and lipids (1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE)) were considered in the preparation of liposomes. DOX was encapsulated within liposome, and ceramide was used as the component of the lipid bilayer. The formulations were optimized for size and size distribution, zeta potential, and DOX encapsulation efficiency (EE). Cytotoxic effect on B16BL6 melanoma cell lines was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The ceramide based liposome formulations generally provided a mean diameter < 181 nm, a zeta potential, + 35 mV, and EE > 90% DOX EE. Co-delivery of DOX and C8-ceramide with DOTAP liposomes demonstrated significantly higher cytotoxicity as compared to DOX liposomes without ceramide (P < 0.001), and also showed enhanced cellular uptake by B16BL6 cell lines. This study provides basis for developing a co-delivery system of DOX and ceramide for lowering the dose and dose-related side effects of DOX for the treatment of melanoma.

KEY WORDS

doxorubicin liposome formulation ceramide melanoma cytotoxicity 

Notes

Funding Information

This work received financial support from Auburn University Research Initiative in Cancer (AURIC) and the intramural grant program (IGP) from the Auburn University AL.

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Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Li Chen
    • 1
  • Hamad Alrbyawi
    • 1
    • 2
  • Ishwor Poudel
    • 1
  • Robert D. Arnold
    • 1
  • R. Jayachandra Babu
    • 1
    Email author
  1. 1.Department of Drug Discovery and Development, Harrison School of PharmacyAuburn UniversityAuburnUSA
  2. 2.Pharmaceutics and Pharmaceutical Technology Department, College of PharmacyTaibah UniversityMedinaSaudi Arabia

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