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Int J Radiat Oncol Biol Phys. 1994 Jul 1;29(4):827-34.

Hyperthermia induces doxorubicin release from long-circulating liposomes and enhances their anti-tumor efficacy.

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  • 1Department of Radiation Oncology, Stanford University School of Medicine, CA 94305-5468.

Abstract

PURPOSE:

To examine the possibility that hyperthermia would accelerate drug release from long-circulating liposomes, and enhance their antitumor activity.

METHODS AND MATERIALS:

Liposomes were prepared by thin film hydration technique. Hyperthermia was induced by ultrasound apparatus and a water bath heating system. The antitumor efficacy of treatment against RIF-1 tumor in C3H mice was evaluated by the tumor growth delay assay.

RESULTS:

In vitro drug release experiments demonstrated that increase in temperature from 37 degrees C to 41 degrees C resulted in about a sixfold increase in doxorubicin (DOX) release in a 1-h period. Increasing the temperature to 43 degrees C, resulted in only a modest additional drug release. Drug uptake studies showed that local hyperthermic treatment immediately following the drug administration dramatically enhanced Stealth liposome-encapsulated doxorubicin (S-DOX) uptake by tumors, but did not do so for free DOX. At 42 degrees C and at a dose of 10 mg/kg, the accumulation of S-DOX was about 10-fold and 2.5-fold higher than that with free drug and S-DOX at 37 degrees C, respectively. The antitumor efficacy study confirmed our hypothesis that the addition of hyperthermia to the treatment of RIF-1 tumors with doxorubicin encapsulated in long-circulating liposomes would enhance antitumor effects. Two hyperthermia treatments given at 24-h intervals appeared to be the most promising method of combining heat and long-circulating liposomes. The increased antitumor activity was not accompanied by increased toxicity, as determined by the body weight of the mice.

CONCLUSION:

Local hyperthermic treatment is able to accelerate DOX release from long-circulating liposomes, increase tumor uptake, and enhance their antitumor efficacy. The combination of local hyperthermia and long-circulating liposomes appears to show considerable promise in the treatment of localized diseases.

PMID:
8040030
[PubMed - indexed for MEDLINE]

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