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. 2010 Aug;27(8):1750-4.
doi: 10.1007/s11095-010-0154-2. Epub 2010 Apr 28.

Hyperthermia and thermosensitive liposomes for improved delivery of chemotherapeutic drugs to solid tumors

Gerben A Koning  1 , Alexander M M Eggermont, Lars H Lindner, Timo L M ten Hagen
Affiliations

Hyperthermia and thermosensitive liposomes for improved delivery of chemotherapeutic drugs to solid tumors

Gerben A Koning et al. Pharm Res. 2010 Aug.

Abstract

Lipid-based nanocarriers or liposomes have been proven successful in the delivery of chemotherapeutic agents and are currently applied clinically in the treatment of various types of cancer. Liposomes offer the advantage of a high drug payload, decreased drug toxicity and enhanced drug accumulation at tumor sites. Increased accumulation is due to the relatively leaky tumor vasculature that allows liposome extravasation. Between different types of tumors and even within one tumor, vascular permeability and thus liposome extravasation may differ greatly. Furthermore, upon accumulation of liposomes in the tumor area, drug bioavailability is not guaranteed. At present, these are the major issues for clinically used liposomal drugs.Mild hyperthermia (HT), the heating of tumor tissue to temperatures of up to 43 degrees C, has been developed in the past decades as an established and efficacious treatment modality in combination with chemo- and radiotherapy. HT can be used to further improve liposomal chemotherapy in two ways: HT is known to increase vascular permeability in solid tumors and may therefore increase levels of liposome accumulation, and thermosensitive liposomes have been developed that can be triggered to release their contents upon hyperthermia. By applying these two strategies, drug delivery to tumors can be strongly enhanced.

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Figures

Fig. 1
Fig. 1
Beneficial effects of hyperthermia on liposome extravasation and drug delivery to solid tumors. A. liposomes by virtue of their prolonged circulation capacity and small size may extravasate from tumor vasculature, which is more permeable than normal vasculature. B. Hyperthermia is known to increase vascular permeability, giving rise to increased levels of liposomes accumulating in the tumor tissue. C. In the interstitial drug release approach a heat trigger is applied to rapidly release drugs from tumor-localized thermosensitive liposomes in close proximity of tumor cells (represented by a red drug gradient in the tumor tissue). Subsequently, the drug is mainly taken up by tumor cells after which it can reach it’s site of action, e.g. the nucleus. D. In the intravascular release approach thermosensitive liposomes reach the heated tumor area and immediately start releasing their drug contents intravascularly (represented by a red drug gradient arising from the tumor blood vessel). Released drugs will be absorbed by the tumor tissue and can be taken up by both tumor and endothelial cells.
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