277723 Liposome-Nanoparticle Assembly Controlled Release

Thursday, November 1, 2012: 1:30 PM
407 (Convention Center )
Matthew Preiss1, Arijit Bose2 and Geoffrey D. Bothun2, (1)Chemical Engineering, University of Rhode Island, Kingston, RI, (2)Department of Chemical Engineering, University of Rhode Island, Kingston, RI

Development of new drug formulations is plagued by high attrition rates. Only about 11% of new promising therapeutic compounds in clinical development are eventually approved. Nearly 70% of drug failures are attributed to poor pharmacokinetics, efficacy, toxicology, clinical safety, and formulation.[1] Liposome-nanoparticle assemblies (LNAs) can help to overcome these deficiencies by providing a delivery vehicle capable of triggered and controlled release. Decorated LNAs (D-LNAs) are formed by embedding hydrophobic nanoparticles in the lipid bilayer. Controlled and triggered release can be achieved by heating the nanoparticles with alternating current electromagnetic fields (EMF) at radiofrequency. Heating causes the lipid bilayer to melt increasing permeability and releasing encapsulated drugs.   

Encapsulation of drugs and release from D-LNAs exposed to EMF is well established. However, the release mechanism of encapsulates remains misunderstood. Our group has demonstrated controlled release from D-LNAs exposed to EMF of smaller drug models (< 600 MW).[2] Previous studies have also established that release is likely due to more than just the change in permeability of the bilayer due to heating.[3] In this research, we investigated the encapsulation and release of large drug models (>3000 MW).  Release of larger drugs will provide insight into the release mechanisms of EMF heated D-LNAs. The encapsulation and stability of D-LNAs will also be investigated to determine the feasibility of D-LNAs as a delivery vehicle for large MW drugs. 

[1] Kola, I., and Landis, J. (2004). Opinion: Can the pharmaceutical industry reduce attrition rates? Nature Reviews Drug Discovery 3, 711-716.

Leeson, P.D., and Davis, A.M. (2004). Time-Related Differences in the Physical Property Profiles of Oral Drugs. Journal of Medicinal Chemistry 47, 6338-6348.

[2] Chen, Y.J., Bose, A., and Bothun, G.D. (2010). Controlled Release from Bilayer-Decorated Magnetoliposomes via Electromagnetic Heating. ACS Nano 4, 3215-3221.

[3] Bothun, G.D., and Priess, M.R. (2011). Bilayer heating in magnetite nanoparticle–liposome dispersions via fluorescence anisotropy. J Coll Inter Sci 357, 70-74.

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