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

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... Full description

Journal Title: Biomaterials 2010, Vol.31(3), pp.541-551
Main Author: Tan, Mei L
Other Authors: Friedhuber, Anna M , Dunstan, Dave E , Choong, Peter F.M , Dass, Crispin R
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 0142-9612 ; E-ISSN: 1878-5905 ; DOI: 10.1016/j.biomaterials.2009.09.069
Link: https://www.sciencedirect.com/science/article/pii/S0142961209010217
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recordid: elsevier_sdoi_10_1016_j_biomaterials_2009_09_069
title: The performance of doxorubicin encapsulated in chitosan–dextran sulphate microparticles in an osteosarcoma model
format: Article
creator:
  • Tan, Mei L
  • Friedhuber, Anna M
  • Dunstan, Dave E
  • Choong, Peter F.M
  • Dass, Crispin R
subjects:
  • Drug Delivery
  • Microparticle
  • Doxorubicin
  • Cancer
  • Osteosarcoma
  • Chitosan
  • Medicine
  • Engineering
ispartof: Biomaterials, 2010, Vol.31(3), pp.541-551
description: 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.
language: eng
source:
identifier: ISSN: 0142-9612 ; E-ISSN: 1878-5905 ; DOI: 10.1016/j.biomaterials.2009.09.069
fulltext: fulltext
issn:
  • 0142-9612
  • 01429612
  • 1878-5905
  • 18785905
url: Link


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titleThe performance of doxorubicin encapsulated in chitosan–dextran sulphate microparticles in an osteosarcoma model
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subjectDrug Delivery ; Microparticle ; Doxorubicin ; Cancer ; Osteosarcoma ; Chitosan ; Medicine ; Engineering
descriptionOsteosarcoma (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.
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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.

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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.

pubElsevier Ltd
doi10.1016/j.biomaterials.2009.09.069
lad01Biomaterials