Effect of liposomal delivery on in vitro antitumor activity of lipophilic conjugates of methotrexate with lipoamino acids.
Some selected lipophilic conjugates of the antifolate drug methotrexate (MTX) with lipoamino acids (LAA), previously described, were incorporated in liposomes with a different composition and charge (neutral, positive, or negative). The properties of the liposomal systems were determined. The inhibitory activity of the conjugates after incorporation in the vesicles was determined in a preliminary assessment against a human erythroleukemic cell line (K562 cells) and compared with the activity of the parent drug and of free conjugates. The influence of liposome surface charge and of the type of conjugate (i.e., in the carboxylic or ester form) on the biological effect is discussed.
Dipartimento di Scienze Farmaceutiche, del Sezione di Patologia Generale, Università di Catania, Catania, Italy. pignatel@unict.it
Rosario
R
Pignatello
Antonina
A
Puleo
Giovanni
G
Puglisi
Luisa
L
Vicari
Angelo
A
Messina
D021542:Amino Acids, Neutral / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000627:therapeutic use*; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D004338:Drug Combinations; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004355:Drug Stability; D006131:Growth Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D006801:Humans; D020014:K562 Cells; D008055:Lipids / Q000737:chemistry; D008081:Liposomes; D008727:Methotrexate / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D010743:Phospholipids / Q000737:chemistry; D013678:Technology, Pharmaceutical
D021542:Amino Acids, Neutral; D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004338:Drug Combinations; D006131:Growth Inhibitors; D008055:Lipids; D008081:Liposomes; D010743:Phospholipids; D008727:Methotrexate