Malathi Anantha

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The incorporation of poly(ethylene glycol) (PEG)-conjugated lipids in lipid-based carriers substantially prolongs the circulation lifetime of liposomes. However, the mechanism(s) by which PEG-lipids achieve this have not been fully elucidated. It is believed that PEG-lipids mediate steric stabilization, ultimately reducing surface-surface interactions(More)
We determined whether the method used to encapsulate irinotecan into 1,2-distearoyl-sn-glycero-phosphocholine/cholesterol (DSPC/Chol; 55:45 mol%) liposomes influenced: (i) irinotecan release rate and (ii) therapeutic efficacy. DSPC/Chol (55:45 mol%) liposomes were prepared with: (i) unbuffered CuSO4; (ii) buffered (pH 7.5) CuSO4; (iii) unbuffered MnSO4 and(More)
BACKGROUND Chemotherapy for glioblastoma (GBM) patients is compromised in part by poor perfusion in the tumor. The present study evaluates how treatment with liposomal formulation of irinotecan (Irinophore C™), and other liposomal anticancer drugs, influence the tumor vasculature of GBM models grown either orthotopically or subcutaneously. METHODS(More)
Cationic liposomes exhibit a propensity to selectively target tumor-associated blood vessels demonstrating potential value as anti-cancer drug delivery vehicles. Their utility however, is hampered by their biological instability and rapid elimination following i.v. administration. Efforts to circumvent rapid plasma elimination have, to date, focused on(More)
PURPOSE To examine the antitumor effects of Irinophore C, a nanopharmaceutical formulation of irinotecan, on the tissue morphology and function of tumor vasculature in HT-29 human colorectal tumors. EXPERIMENTAL DESIGN Fluorescence microscopy was used to map and quantify changes in tissue density, tumor vasculature, hypoxia, and the distribution of(More)
PURPOSE To assess the pharmacokinetics, tumor drug accumulation, and therapeutic activity of Irinophore C, a novel liposomal formulation of irinotecan (CPT-11). EXPERIMENTAL DESIGN The plasma lactone/carboxy levels of CPT-11 and SN-38 were determined in mice after a single i.v. dose of irinotecan (Camptosar), or Irinophore C, and the plasma t(1/2), plasma(More)
PURPOSE The use of in vitro drug cytotoxicity assays for the assessment of drug-drug interactions that lead to synergy may not take into account the many cellular determinants responsible for combination effects. Administration of the anticancer drug CPT-11, for example, is associated with rapid conversion of drug from its active lactone form to the(More)
These studies describe the role of transition metal ions in the liposomal encapsulation of topotecan. Liposomes (1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and cholesterol (CH) (55:45, mole ratio)) were prepared with manganese (Mn), copper (Cu), zinc (Zn) or cobalt (Co) ion gradients (metal inside). Subsequently, topotecan was added to the liposome(More)
PURPOSE To determine whether entrapped transition metals could mediate the active encapsulation of the anticancer drug irinotecan into preformed liposomes. Further, to establish that metal complexation could stabilize liposomal irinotecan in the therapeutically active lactone conformation. MATERIALS AND METHODS Irinotecan was added to preformed(More)
PURPOSE To investigate the use of liposomal irinotecan (Irinophore C™) plus or minus 5-fluorouracil (5-FU) for the treatment of colorectal cancer. EXPERIMENTAL DESIGN The effect of irinotecan (IRI) and/or 5-FU exposure times on cytotoxicity was assessed in vitro against HT-29 or LS174T human colon carcinoma cells. The pharmacokinetics and biodistribution(More)