Polymer carriers hold promise to improve drug solubility, circulation, biodistribution, and release rate, enhancing therapeutic efficacy. Furthermore, targeting of carriers to cell markers located in disease areas and involved in endocytic transport facilitates intracellular drug delivery, a requirement for a number of therapeutic goals. We are developing strategies to enhance delivery of polymer carriers to intercellular adhesion molecule 1 (ICAM-1), a protein expressed in many diseases. Using in vitro, cell culture and mouse models, we demonstrated that this strategy enhances delivery of therapeutics to target organs and improves uptake into and transport across cells, providing enhanced effects. This approach is being optimized by modulating parameters governing carrier performance, including those intrinsic to the physiological system (disease status, blood flow, target epitopes, signaling molecules, cytoskeleton, lipid domains) and those pertinent to carrier design (size, shape, avidity). The presentation will highlight main findings concerning these aspects.Funding: NIH R01-HL98416 and AHA 09BGIA2450014.

Controlling ICAM-1 targeting and subcellular transport of therapeutic polymer carriers

244th National Meeting (2012)

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