Biodegradable nanoparticles formulated from poly (d,l-lactide-co-glycolide) (PLGA) have been extensively investigated for sustained and targeted/localized delivery of different agents including plasmid DNA, proteins and peptides and low molecular weight compounds. Research about the mechanism of intracellular uptake of nanoparticles, their trafficking and sorting into different intracellular compartments, and the mechanism of enhanced therapeutic efficacy of nanoparticle-encapsulated agent at cellular level is more recent and is the primary focus of the review. Recent studies in our laboratory demonstrated rapid escape of PLGA nanoparticles from the endo-lysosomal compartment into cytosol following their uptake. Based on the above mechanism, various potential applications of nanoparticles for delivery of therapeutic agents to the cells and tissue are discussed.
Bibliographical noteFunding Information:
JP is supported by a Predoctoral Fellowship from American Heart Association, the Heartland Affiliate. The work described in the review is partially contributed by Dr. Wenzong Zhou, Swayam Prabha, Jasmine Davda, and Dr. Sanjeeb K. Sahoo in Dr. Labhasetwar’s laboratory. Some of the work described in the review was carried out in collaboration with Dr. Robert J. Levy, University of Pennsylvania, Philadelphia and Dr. Gordon L. Amidon, University of Michigan, Ann Arbor. Grant support from the National Institutes of Health, Heart, Lung, and Blood Institute (HL 57234) and the Nebraska Research Initiative-Gene Therapy Program. We would like to thank Janice Taylor and Tom Bargar for their assistance with microscopic studies and Ms. Elaine Payne for secretarial assistance.
- Biodegradable polymers
- Gene therapy
- Protein delivery
- Sustained release