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The performance of doxorubicin encapsulated in chitosan–dextran sulphate microparticles in an osteosarcoma model

Tan, Mei Lin and Friedhuber, Anna M and Dunstan, David E and Choong, Peter F. M and Dass, Crispin R (2010) The performance of doxorubicin encapsulated in chitosan–dextran sulphate microparticles in an osteosarcoma model. Biomaterials, 31 (3). pp. 541-551. ISSN 0142-9612

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Abstract

Osteosarcoma (OS) is the most common primary bone cancer affecting children and adolescents. It is potentially debilitating and fatal due to pulmonary metastasis. A common management strategy, chemotherapy, has a 10-year disease-free survival of approximately 60%. However, a targeted approach to OS tumor inhibition is still lacking, calling for improved management strategies. A frontline drug for OS, doxorubicin (DOX), causes multiple side-effects (example myelosuppression, heart failure, hepatic toxicity, alopecia) in patients, especially in high doses required to control tumor growth. A drug delivery system (DDS) was developed to deliver DOX specifically to tumor sites. Through DOX encapsulation into chitosan DDS via the complex coacervation method with dextran sulphate, novel DOX microparticles (DMPs), with a DOX loading content of more than 99%, were formed. Multiple optimisation steps produced DMPs which caused OS cell death through apoptosis, necrosis and autophagic cell death. Treatment of mice bearing orthotopic OS with DMP decreased tumor volume, decreased bone lysis, and reduced secondary metastasis to the lungs. DMP-treated mice also maintained their weight and did not appear to suffer from any visible side-effects such as heart failure or dry skin. Thus, DMP may prove to be a useful DDS platform clinically provided further studies are performed to rigorously validate this technology.

Item Type: Article
Uncontrolled Keywords: ResPubID21872, drug delivery, microparticle, doxorubicin, cancer, osteosarcoma, chitosan
Subjects: Faculty/School/Research Centre/Department > School of Biomedical and Health Sciences
FOR Classification > 1112 Oncology and Carcinogenesis
SEO Classification > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions)
Depositing User: VUIR
Date Deposited: 25 Jun 2012 04:16
Last Modified: 08 Feb 2015 23:14
URI: http://vuir.vu.edu.au/id/eprint/7576
DOI: 10.1016/j.biomaterials.2009.09.069
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Citations in Scopus: 34 - View on Scopus

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