期刊
JOURNAL OF CONTROLLED RELEASE
卷 134, 期 2, 页码 118-124出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2008.11.016
关键词
Photodynamic therapy; mTHPC; Foslip; Liposome; Pharmacokinetics; Intratumoral distribution; Two photon microscopy
资金
- Regional Council of Lorraine
- Alexis Vautrin Cancer Center
- French Ligue Nationale Contre le Cancer [54, 55, 57]
Foslip is a recently designed third generation photosensitiser based on unilamellar dipalmitoylphosphatidylcholine/dipalmitoylphosphatidylglycerol (DPPC/DPPG) liposomal formulations of meta-tetra(hydroxyphenyl)chlorine (mTHPC). The present study investigates Foslip behaviour and its photodynamic efficiency in EMT6 xenografted nude mice at different times following i.v. administration of 0.3 mg kg(-1) mTHPC in a Foslip formulation. Plasma pharmacokinetics and biodistribution were studied by high performance liquid chromatography and were described by a three compartments analysis with half-lifes of 0.13, 4.31 and 35.7 h. The highest turnout to muscle ratios were observed at 6 and 15 h post-administration. Intratumoral distribution was carried out using two photon excitation confocal microscopy. Progressive efflux from the vascular compartment was noted in favour of tumour parenchyma, which was almost completed at 15 h. The best turnout response was obtained for a drug-light interval of 6 h, interval for which mTHPC was present in both endothelial and parenchyma cells. Tumour and plasma concentrations however were far below their maximal values. Based on these observations, we assume that the presence of mTHPC in both vasculature and tumour cells is required for optimal PDT efficacy. (C) 2008 Elsevier B.V. All rights reserved.
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