Liposome encapsulation of lipophilic N-Alkyl-propanediamine platinum complexes: Impact on their cytotoxic activity and influence of the carbon chain length

Abstract

Antitumor platinum(II) complexes derived from N-alkyl-propanediamine differing in the length of their carbon chain (C8, C10, C12 and C14) were incorporated in liposomes and the cytotoxic activity of these formulations was evaluated against tumor (A549, MDA-MB-231, B16-F1 and B16-F10) and non-tumor (BHK-21 and CHO) cell lines. Stable and monodisperse liposome suspensions incorporating the platinum complexes were obtained from the lipid composition consisting of distearoyl-sn-glycero-3-phosphocholine, cholesterol and 1,2-distearoyl-sn-glycero-3-phophoethanolamine-N-(methoxy(polyethylene glycol)-2000) at 5:3:0.3 molar ratio. The entrapment efficiency (EE%) of the platinum complexes in liposomes increased with the carbon chain length. EE% was higher than 80% in C12-and C14-derivatives. The effect of liposome encapsulation on the cytotoxic activity of the complexes was found to depend on the carbon chain length. These data indicate that the highest drug bioavailability from liposome formulations was achieved with the complex showing intermediate carbon chain length and partition between the liposome membrane and aqueous phase. © 2010 Sociedade Brasileira de Química.