Liposomes as a drug carrier system for cis-diamminedichloroplatinum (II). I. Binding capacity, stability and tumor cell growth inhibition in vitro

Abstract

We investigated the potential of liposomes as drug carrier for cis-diamminedichloroplatinum(II) (cis-DDP). The binding capacity, Pt release on storage, and in vitro antitumor activity was determined. It was found that the encapsulation efficiency was dependent on the NaCl concentration of the hydration medium in which cis-DDP was dissolved. In addition, cis-DDP liposomes prepared by hydration with 0.9% NaCl showed a relatively high drug leakage on storage. For cis-DDP liposomes prepared by hydration with 0.2% NaCl/4.2% mannitol or 5% mannitol the fraction of the drug associated with the liposomes was more than 90% after prolonged storage at 4°C for 50 days. Compared to the activity of free cis-DDP, cis-DDP encapsulated in liposomes showed a decreased antitumor activity in vitro against a murine gastric squamous cell carcinoma. This suggested that the antitumor activity of liposomal cis-DDP was due to leakage of cisDDP from the liposomes. However, cis-DDP recovered from PC/PS/Chol liposomes after 3 cycles of freezing and thawing was equally active as free cisDDP. From the present study it is concluded that cisDDP liposomes prepared by hydration with 5% mannitol or 0.2% NaCl/4.2% mannitol have a relatively high binding capacity, and high stability against drug leakage.