Abstract:
:Annamycin (Ann) is a non-cross-resistant lipophilic anthracycline antiobiotic optimally suited for liposome delivery. We studied how vesicle size and presence of phospholipids with a high phase transition temperature and monosialoganglioside (GM I) in the liposome bilayers affect the pharmacokinetics, tumor selectivity and toxicity of Ann. Entrapment of Ann in multilamellar vesicles (L-Ann) resulted in a 20% lower heart AUC and a 30-40% higher tumor and liver AUC. Reduction of the liposome size from 1.6 to 0.03 microns increased Ann plasma circulation time and tumor AUC by 2-fold, enhanced Ann tumor selectivity and decreased Ann subacute toxicity by 2-fold. The presence of phospholipids with a high phase transition temperature and GMI in the liposome bilayers further prolonged Ann plasma circulation time by 2- to 4-fold, did not increase Ann tumor AUC and moderately increased Ann subacute toxicity. The anti-tumor activity of Ann correlated with the tumor AUC achieved with each particular formulation. Our results strongly suggest that vesicle size may be an important determinant of the therapeutic index of liposomal Ann, but they fail to demonstrate a beneficial tumor-targeting effect of liposomes composed of GMI and phospholipids with a high phase transition temperature, as has been reported for the hydrophilic parent compound doxorubicin.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Zou Y,Ling YH,Reddy S,Priebe W,Perez-Soler Rdoi
10.1002/ijc.2910610513subject
Has Abstractpub_date
1995-05-29 00:00:00pages
666-71issue
5eissn
0020-7136issn
1097-0215journal_volume
61pub_type
杂志文章abstract::Human papillomavirus (HPV) is now recognised as a major aetiological agent in the pathogenesis of oropharyngeal carcinoma (OPC). HPV-positive tumours are associated with better outcomes compared to HPV-negative tumours, possibly due to differences in their aetiology and/or the tumour microenvironment. Increased number...
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