Preparation, characterisation and maintenance of drug efficacy of doxorubicin-loaded human serum albumin (HSA) nanoparticles.

Human serum albumin (HSA) nanoparticles represent promising drug carrier systems. Binding of cytostatics to HSA nanoparticles may diminish their toxicity, optimise their body distribution and/or may overcome multidrug resistance. In the present study, doxorubicin-loaded HSA nanoparticle preparations were prepared. Doxorubicin was loaded to the HSA nanoparticles either by adsorption to the nanoparticles' surfaces or by incorporation into the particle matrix. Both loading strategies resulted in HSA nanoparticles of a size range between 150nm and 500nm with a loading efficiency of 70-95%. The influence on cell viability of the resulting nanoparticles was investigated in two different neuroblastoma cell lines. The anti-cancer effects of the drug-loaded nanoparticles were increased in comparison to doxorubicin solution. Based on these result a standard protocol for the preparation of doxorubicin-loaded HSA nanoparticles for further antitumoural studies was established.

[1]  F. Piquard,et al.  Safety and efficacy of a new transpulmonary echo contrast agent in echocardiographic studies in patients. , 1993, Journal of the American College of Cardiology.

[2]  K. Strebhardt,et al.  Highly Specific HER2-mediated Cellular Uptake of Antibody-modified Nanoparticles in Tumour Cells , 2004, Journal of drug targeting.

[3]  C. Twelves,et al.  Activity of Doxorubicin Covalently Bound to a Novel Human Serum Albumin Microcapsule , 2004, Investigational New Drugs.

[4]  F J Ten Cate,et al.  Safety and efficacy of a new transpulmonary ultrasound contrast agent: initial multicenter clinical results. , 1990, Journal of the American College of Cardiology.

[5]  D C Carter,et al.  Structure of serum albumin. , 1994, Advances in protein chemistry.

[6]  K. Geiger,et al.  Chemotherapy of glioblastoma in rats using doxorubicin‐loaded nanoparticles , 2004, International journal of cancer.

[7]  R. Nicholson,et al.  Polymer-drug conjugates: towards a novel approach for the treatment of endrocine-related cancer. , 2005, Endocrine-related cancer.

[8]  P. Couvreur,et al.  Doxorubicin-loaded nanospheres bypass tumor cell multidrug resistance. , 1992, Biochemical pharmacology.

[9]  D. Begley,et al.  Biodistribution of polysorbate 80-coated doxorubicin-loaded [14C]-poly(butyl cyanoacrylate) nanoparticles after intravenous administration to glioblastoma-bearing rats , 2006, Journal of drug targeting.

[10]  H. Maeda,et al.  Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[11]  L. Gianni,et al.  Anthracyclines: Molecular Advances and Pharmacologic Developments in Antitumor Activity and Cardiotoxicity , 2004, Pharmacological Reviews.

[12]  M. Chevallier,et al.  Increase of doxorubicin sensitivity by doxorubicin-loading into nanoparticles for hepatocellular carcinoma cells in vitro and in vivo. , 2005, Journal of hepatology.

[13]  K. Joh,et al.  Bovine serum albumin-doxorubicin conjugate overcomes multidrug resistance in a rat hepatoma. , 1993, Cancer research.

[14]  H. Tajmir-Riahi,et al.  Interaction of cisplatin with human serum albumin. Drug binding mode and protein secondary structure. , 1998, Biochimica et biophysica acta.

[15]  F Lechenault,et al.  Transferrin conjugates of doxorubicin: synthesis, characterization, cellular uptake, and in vitro efficacy. , 1998, Journal of pharmaceutical sciences.

[16]  P. Singal,et al.  Adriamycin-induced heart failure: mechanisms and modulation , 2000, Molecular and Cellular Biochemistry.

[17]  R. Levy,et al.  The covalent binding of daunomycin and adriamycin to antibodies, with retention of both drug and antibody activities. , 1975, Cancer research.

[18]  R. Duncan The dawning era of polymer therapeutics , 2003, Nature Reviews Drug Discovery.

[19]  C. Unger,et al.  Preparation, characterization and in vitro efficacy of albumin conjugates of doxorubicin. , 1998, Biological & pharmaceutical bulletin.

[20]  K. Strebhardt,et al.  Tumour cell delivery of antisense oligonuclceotides by human serum albumin nanoparticles. , 2004, Journal of controlled release : official journal of the Controlled Release Society.

[21]  F. Forni,et al.  Doxorubicin-loaded gelatin nanoparticles stabilized by glutaraldehyde: Involvement of the drug in the cross-linking process , 1997 .

[22]  T. Park,et al.  Biodegradable Nanoparticles Containing Doxorubicin-PLGA Conjugate for Sustained Release , 1999, Pharmaceutical Research.

[23]  Patrick Soon-Shiong,et al.  Phase I and pharmacokinetic study of ABI-007, a Cremophor-free, protein-stabilized, nanoparticle formulation of paclitaxel. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[24]  T. Mosmann Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. , 1983, Journal of immunological methods.

[25]  H. Doerr,et al.  Aphidicolin selectively kills neuroblastoma cells in vitro. , 1992, Cancer letters.

[26]  H. Tajmir-Riahi,et al.  Interaction of taxol with human serum albumin. , 2000, Biochimica et biophysica acta.

[27]  V. Rizzo,et al.  HPLC methods for the determination of bound and free doxorubicin, and of bound and free galactosamine, in methacrylamide polymer-drug conjugates. , 1996, Journal of pharmaceutical and biomedical analysis.

[28]  F. Forni,et al.  Dynamic dialysis for the drug release evaluation from doxorubicin-gelatin nanoparticle conjugates. , 1999, International journal of pharmaceutics.

[29]  K. Langer,et al.  Desolvation process and surface characteristics of HSA-nanoparticles. , 2000, International journal of pharmaceutics.

[30]  H von Briesen,et al.  Optimization of the preparation process for human serum albumin (HSA) nanoparticles. , 2003, International journal of pharmaceutics.

[31]  K. Ulbrich,et al.  The pharmacokinetics of polymer-bound adriamycin. , 1990, Biochemical pharmacology.

[32]  F. Garbagnati,et al.  Intraarterial chemotherapy with polyoxyethylated castor oil free paclitaxel, incorporated in albumin nanoparticles (ABI‐007) , 2001, Cancer.

[33]  J. Kreuter,et al.  Significant Transport of Doxorubicin into the Brain with Polysorbate 80-Coated Nanoparticles , 1999, Pharmaceutical Research.