Increased systemic stability, tumor accumulation and in vitro and in vivo efficacy of a secretory phospholipase 2-degradable liposomal form of cisplatin.

摘要: AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA 5618 Cisplatin is one of the most potent antitumor agents known, displaying activity against a large number solid tumors. However, side-effects such as nephrotoxicity and neurotoxicity well cellular resistance to agent mean that this not first choice drug in many cancers. An improved delivery system which expected reduce these side effects highly desirable. We have designed liposomal form cisplatin (LiplaCis) can be specifically degraded by secretory phospholipase A2 (sPLA2). sPLA2 often present tumor tissues, either expressed cancerous cells or infiltrating immune thereby assuring site-specific release micro-environment. The specificity sPLA2-mediated was demonstrated vitro with resistant LiplaCis absence sPLA2. In contrast, presence IC50 values are lower than for free due simultaneous lysolipids from liposomes. vivo pharmacokinetic experiments rats mice show an increased stability plasma effect after >14 days. Xenograft studies nude using mouse mammary carcinoma model MT-3, colon CT-26 human Colo205 revealed long-lasting accumulation within hours administration. Efficacy MT-3 -model showed elimination compared similar toxicity. Thus, perform better clinic phase will initiated early 2008.