2008 NSTI Nanotechnology Conference and Trade Show - Nanotech 2008 - 11th Annual

Partnering Events:

TechConnect Summit
Clean Technology 2008

Long-circulating PEGylated PLGA nanoparticles for Drug Delivery

J. Park, P.M. Fong, K.S. Russell, W.M. Saltzman, T.M. Fahmy
Carigent Therapeutics, US

Keywords:
PLGA, PEG, nanoparticle, drug delivery

Abstract:
The encapsulation of cytotoxic chemotherapeutic agents in biodegradable PLGA nanoparticles may offer advantages over other delivery systems, including liposomes. These include the ability to encapsulate a wide variety of agents (hydrophilic, hydrophobic, DNA, and protein), tailor drug release, and manipulate nanoparticle size and localization of dose. However, one of the major hurdles to creating a PLGA nanoparticle drug delivery platform has been the difficulty in creating functionalized surfaces for the attachment of shielding ligands (i.e. PEG) or targeting ligands (i.e. monoclonal antibodies). Previous ligand coupling techniques have commonly suffered from low surface densities or poor robustness. We present a unique avidin-based surface modification technique that was used in this investigation to create long-circulating PEGylated PLGA nanoparticles for the delivery of doxorubicin. An avidin-lipid bioconjugate was used to create 5% (w/w) doxorubicin-loaded, avidin-coated PLGA nanoparticles with mean diameter of 130 nm, where the avidin-biotin linker system was used to control PEG conjugation to the surface of the nanoparticles. PEGylation was found to dramatically increase nanoparticle/drug circulation time while resulting in decreased cardiotoxicity similar to that of Doxil, the current gold standard for long-circulating doxorubicin delivery vehicles. Efficacy against lymphoma in vitro and in vivo was not compromised.


Nanotech 2008 Conference Program Abstract