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.

[1]  S. Simões,et al.  On the mechanisms of internalization and intracellular delivery mediated by pH-sensitive liposomes. , 2001, Biochimica et biophysica acta.

[2]  C. Di Giacomo,et al.  Lipophilic methotrexate conjugates with glucose‐lipoamino acid moieties: Synthesis and in vitro antitumor activity , 2001 .

[3]  C. Kim,et al.  Prolonged Blood Circulation of Methotrexate by Modulation of Liposomal Composition , 2001, Drug delivery.

[4]  C. Di Giacomo,et al.  Lipophilic methotrexate conjugates with antitumor activity. , 2000, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[5]  Maruyama,et al.  Possibility of active targeting to tumor tissues with liposomes. , 1999, Advanced drug delivery reviews.

[6]  G. Jansen,et al.  Lipoamino acid conjugates of methotrexate with antitumor activity. , 1998, Journal of pharmaceutical sciences.

[7]  I. Toth,et al.  Novel liposaccharide conjugates for drug and peptide delivery. , 1998, Journal of pharmaceutical sciences.

[8]  G. Peters,et al.  Carrier- and receptor-mediated transport of folate antagonists targeting folate-dependent enzymes: correlates of molecular-structure and biological activity. , 1995, Molecular pharmacology.

[9]  I. Toth A novel chemical approach to drug delivery: lipidic amino acid conjugates. , 1994, Journal of drug targeting.

[10]  S. R. Chhabra,et al.  The chemistry of methotrexate and its analogues , 1988, Medicinal research reviews.

[11]  S. Fujime,et al.  [Dynamic light-scattering]. , 1985, Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme.

[12]  R. Pecora Dynamic Light Scattering , 1985 .

[13]  L. Matherly,et al.  The cellular pharmacology of methotrexate. , 1985, Pharmacology & therapeutics.