Reduced UV-Induced Degradation of Doxorubicin Encapsulated in Polyethyleneglycol-Coated Liposomes

AbstractPurpose. The aim of this study was to investigate the stability of doxorubicin encapsulated in polyethyleneglycol-coated liposomes (Doxil™) under UV-A light. Methods. High performance liquid chromatography and a fluorimetric method were used to quantify doxorubicin in bulk solution and doxorubicin in Doxil formulation. Results. The photodegradation of Doxil was significantly lower in comparison to the photodegradation of the free drug and showed no concentration dependency at the measured concentration range of 5−50 μg/ml. During and after UV-A irradiation, there was no leakage of the drug from liposomes to the medium. After induced leakage of doxorubicin from the liposomes by the ionophore nigericin, the degradation kinetics of Doxil were identical to that of free doxorubicin. Conclusions. High intraliposomal doxorubicin concentration and intraliposomal acidic pH are the two critical factors that protect DXR in Doxil from UV-A degradation.

[1]  Y. Barenholz,et al.  In vitro cytotoxicity of liposome-encapsulated doxorubicin: dependence on liposome composition and drug release. , 1992, Biochimica et biophysica acta.

[2]  D. Crommelin,et al.  The interaction of cytostatic drugs with adsorbents in aqueous media. The potential implications for liposome preparation. , 1985, Biochimica et biophysica acta.

[3]  G. Storm,et al.  Doxorubicin decomposition on storage: effect of pH, type of buffer and liposome encapsulation , 1985 .

[4]  A. Gabizon Selective tumor localization and improved therapeutic index of anthracyclines encapsulated in long-circulating liposomes. , 1992, Cancer research.

[5]  Y. Barenholz,et al.  Liposomes: preparation, characterization, and preservation. , 2006 .

[6]  A. Gabizon,et al.  Liposome circulation time and tumor targeting: implications for cancer chemotherapy , 1995 .

[7]  Y. Barenholz,et al.  Prolonged circulation time and enhanced accumulation in malignant exudates of doxorubicin encapsulated in polyethylene-glycol coated liposomes. , 1994, Cancer research.

[8]  A. Ramu,et al.  The inactivation of doxorubicin by long ultraviolet light , 1997, Cancer Chemotherapy and Pharmacology.

[9]  Y. Barenholz,et al.  Stability of liposomal doxorubicin formulations: Problems and prospects , 1993, Medicinal research reviews.

[10]  Y. Barenholz,et al.  Gelation of liposome interior A novel method for drug encapsulation , 1992, FEBS letters.

[11]  Y. Barenholz,et al.  Transmembrane ammonium sulfate gradients in liposomes produce efficient and stable entrapment of amphipathic weak bases. , 1993, Biochimica et biophysica acta.

[12]  A. Guarino,et al.  Photolytic degradation of adriamycin , 1980, The Journal of pharmacy and pharmacology.

[13]  W. J. Irwin,et al.  PHOTODEGRADATION OF DOXORUBICIN, DAUNORUBICIN and EPIRUBICIN MEASURED BY HIGH‐PERFORMANCE LIQUID CHROMATOGRAPHY , 1990, Journal of clinical pharmacy and therapeutics.

[14]  P. Riesz,et al.  Photoinduced reactions of anthraquinone antitumor agents with peptides and nucleic acid bases: an electron spin resonance and spin trapping study. , 1985, Archives of biochemistry and biophysics.

[15]  P. Riesz,et al.  Photogeneration of superoxide by adriamycin and daunomycin , 1983, FEBS letters.

[16]  Y. Barenholz,et al.  Optimization and upscaling of doxorubicin-containing liposomes for clinical use. , 1990, Journal of pharmaceutical sciences.

[17]  F. Demsar,et al.  Electron spin resonance imaging of tissues with lipid‐rich areas , 1988, Magnetic resonance in medicine.

[18]  A. Gabizon,et al.  Sterically stabilized liposomes: a hypothesis on the molecular origin of the extended circulation times. , 1991, Biochimica et biophysica acta.

[19]  Y. Barenholz,et al.  Development of liposomal anthracyclines: from basics to clinical applications. , 1998, Journal of controlled release : official journal of the Controlled Release Society.

[20]  F. Berthou,et al.  Study of doxorubicin photodegradation in plasma, urine and cell culture medium by HPLC. , 1987, Biomedical chromatography : BMC.

[21]  Y. Yarden,et al.  Targeting of stealth liposomes to erbB-2 (Her/2) receptor: in vitro and in vivo studies. , 1996, British Journal of Cancer.