Abstract
Background:
Hepatocellular carcinomas are frequently nonresponsive to systemically delivered drugs. Local delivery provides an alternative to systemic administration, maximizing the dose delivered to the tumor, achieving sustained elevated concentrations of the drug, while minimizing systemic exposure.
Results:
Ultrasound-guided deposition of doxorubicin (Dox)-eluting in situ forming implants (ISFI) in an orthotopic tumor model significantly lowers systemic drug levels. As much as 60 µg Dox/g tumors were observed 21 days after ISFI injection. Tumors treated with Dox implants also showed a considerable reduction in progression at 21 days.
Conclusion:
Dox-eluting ISFIs provide a promising platform for the treatment of hepatocellular carcinomas by which drug can be delivered directly into the lesion, bypassing distribution and elimination by the circulatory system.
Keywords:
drug delivery; hepatocellular carcinoma; in situ forming implant; phase inversion; ultrasound.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Administration, Intravenous
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Animals
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Antibiotics, Antineoplastic / administration & dosage*
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Antibiotics, Antineoplastic / chemistry
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Antibiotics, Antineoplastic / toxicity
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Carcinoma, Hepatocellular / diagnostic imaging
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Carcinoma, Hepatocellular / drug therapy*
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Cell Line, Tumor
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Cell Survival / drug effects
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Doxorubicin / administration & dosage*
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Doxorubicin / chemistry
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Doxorubicin / toxicity
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Drug Carriers / chemistry*
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Feasibility Studies
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Humans
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Lactic Acid / chemistry
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Liver Neoplasms / diagnostic imaging
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Liver Neoplasms / drug therapy*
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Male
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Polyglycolic Acid / chemistry
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Polylactic Acid-Polyglycolic Acid Copolymer
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Rats
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Rats, Sprague-Dawley
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Time-Lapse Imaging
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Tissue Distribution
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Transplantation, Heterologous
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Ultrasonography
Substances
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Antibiotics, Antineoplastic
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Drug Carriers
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Polylactic Acid-Polyglycolic Acid Copolymer
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Polyglycolic Acid
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Lactic Acid
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Doxorubicin