Targeted and triggerable lipid carriers for the in vitro delivery of water soluble compounds
Abstract
This work addresses two of the most taxing challenges facing conventional liposomal drug delivery, selective targeting of therapeutic agents to tumor tissue, and controlled release of appreciable quantities of entrapped contents via efficient membrane translocation upon delivery to the targeted site. The development of novel, biocompatible lipid carriers of water-soluble agents that can be triggered to rapidly release contents upon exposure to an acidic stimulus was examined for its potential to be applied to the site-specific delivery of encapsulated materials at biological targets. Folate-targeted diplasmenylcholine (1,2-di-O-(Z-1′-hexadecenyl)- sn-glycero-3-phosphocholine; DPPlsC) liposomes were used to deliver dyes, photosensitizers, and proteins to targeted KB cells. The mechanism of release, as well as the molecular weight limitations for endosomal escape, were investigated via confocal microscopy. Confocal microscopy studies revealed that the water-soluble sensitizer, AlPcS44− , was initially localized within lysosomes when delivered via DPPlsC:folate liposomes. Extended exposure of these AlPcS44−/DPPlsC liposomes to the lysosomal environment, however, lead to diffuse perinuclear staining, suggesting that DPPlsC degradation products may mediate the escape of the sensitizer into the cytoplasm. Enhanced phototoxicity of KB cells to AlPcS44− was observed when delivered via this targeted, acid triggerable carrier compared to nontargeted, and acid insensitive liposomes.
Degree
Ph.D.
Advisors
Thompson, Purdue University.
Subject Area
Organic chemistry|Biochemistry|Pharmacology
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