Controlled release of liposome-encapsulated temozolomide for brain tumour treatment by convection-enhanced delivery

Convection-enhanced delivery (CED) is a promising technique for the delivery of drugs directly into the central nervous system (CNS) and, more specifically, the brain. CED can increase drug concentration within a brain tumour, thereby improving the therapeutic efficacy and limiting the systemic toxicity of tumoricidal agents. In this study, we evaluated a drug-liposome construct in vitro and in vivo using U87 tumour-bearing nude mice. Dipalmitoylphosphatidylcholine (DPPC)-based liposomes were designed to deliver a lipophilic temozolomide (TMZ) formulation (LipoTMZ). The LipoTMZ displayed good release of TMZ in vitro over a suitable range of time and temperatures. Encapsulating the TMZ into liposomes enhanced its tumoricidal activity against U87MG human glioma cells. The LipoTMZ also displayed good release and distribution of TMZ when delivered intracerebrally to U87MG tumour-bearing mice by CED infusion. Histological examination revealed that CED did not damage normal brain tissue. Our data indicate that CED was an effective method to deliver LipoTMZ to U87MG tumour-bearing mice, significantly inhibiting tumour growth without evidence of systemic toxicity.