Abstract
Liposomes have long been effective delivery vehicles for transport of toxins to peripheral cancers. The combination of convection-enhanced delivery (CED) with liposomal toxins was originally proposed to circumvent the limited delivery of intravascular liposomes to the central nervous system (CNS) due to the blood-brain-barrier (BBB). CED offers markedly improved distribution of infused therapeutics within the CNS compared to direct injection or via drug eluting polymers, both of which depend on diffusion for parenchymal distribution. This review examines the basis for improved delivery of liposomal toxins via CED within the CNS, and discusses preclinical and clinical experience with these therapeutic techniques. How CED and liposomal technologies may influence future neurooncologic treatments are also considered.
Highlights
The effective delivery of therapeutic agents via the vasculature to the central nervous system (CNS)is significantly affected by the presence of the blood-brain-barrier (BBB) [1]
The circulating half-life of these liposomal toxins (LT) can be enhanced further by the addition of a polyethylene glycol (PEG) coat to the liposomal surface, which can be modified with specific targeting molecules that increase the specificity for receptor-mediated endocytosis, or other cellular incorporation strategies in target cells
Tissue affinities for chemotherapeutic agents delivered via convection-enhanced delivery (CED) were noted to be a limiting factor for parenchymal volume of distribution (Vd) within the CNS [147], despite being significantly greater than via diffusion-based delivery methods
Summary
The effective delivery of therapeutic agents via the vasculature to the central nervous system (CNS). These same alterations in ECS structure may hinder the diffusion of certain neuroactive substances or therapeutic molecules within neoplastic tissue [78] These barriers to diffusion and convection, directly related to the tumor parenchyma, provide a less permeable medium for CED, and even less so for diffusion-based delivery options. Despite adequate coverage of a tumor volume with an effective therapeutic via CED, the rapid clearance of the drug due to this outward flow of ECF (and reduced concentration-time product) may provide little or no clinical efficacy [76,81] Such interstitial pressures and fluid flows make it even less likely that peripherally placed diffusion-based therapeutics will influence the tumor core. Allow a better estimation and standardization of the therapeutic contact time
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