Doxil release

Current opinion concerning the mechanism of delivery of liposomal therapeutics to tumors is that, once in the tumor, standard liposomes are localized in the extra-cellular fluid that surrounds the tumor cell but do not enter it i 8 ii Therefore, for delivery of the therapeutic agent, the drug must first be released into the extra-cellular fluid, from where it must then diffuse into the cell. There is the evidence that doxorubicin is released efficiently from Doxil liposomes, to be taken up by the cell in ovarian cancer and Kaposi s sarcoma. Concentrations of doxorubicin achieved in cells have been estimated as up to 13 times higher from Stealth liposomes than with a simple doxorubicin injection in patients undergoing treatment of Kaposi s sarcoma. hi contrast, evidence from the use of cisplatin seems less definitive. In studies comparing Stealth liposomal cisplatin (SPl-077) with standard cisplatin in... 

Fig. 15 A Polymer-enzyme liposome therapy (PELT) relies on the liberation of drug from liposomes by the action of a polymer-phospholipase conjugate. B PEGylated liposomal doxorubicin (Doxil) activated by HPMA copolymer-Gly-Gly-phospholipase C conjugate. C Comparison of enzymatic activity of free phospholipase C and HPMA copolymer Gly-Gly-phospholipase C in vitro. Release of doxorubicin from Daunoxomes in the presence of phospholipase C ( ), HPMA copolymer-Gly-Gly-phospholipase C (A) or Triton X-100 (1%) ( ) and in the absence of enzyme as a control ( ) (R. Satchi and R. Duncan, unpublished results)...

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