Though researchers have made substantial progress in developing drug-ferrying nanoparticles that successfully target tumor cells in living animals, including humans, investigators have only now started the detailed work needed to identify formulation parameters that would optimize drug delivery to malignant cells. Now, in one of the first studies of its kind, a team of scientists at the MIT-Harvard Center for Cancer Nanotechnology Excellence (CCNE) have performed systematic experiments aimed at identifying how nanoparticle formulations affect drug delivery in the body.
Reporting its work in the journal Biomaterials, a team of researchers led by Omid Farokhzad, M.D., of the Harvard Medical School and a member of the MIT-Harvard CCNE, and Robert Langer, Ph.D., of the Massachusetts Institute of Technology and co-principal investigator of the MIT-Harvard CCNE, studied the effects of altering nanoparticle polymer composition, drug loading, and solvents on the ability of the resulting nanoparticles to target and deliver drugs to tumors. As a targeting agent for all the polymer nanoparticles studied, the researchers used a molecule that recognizes the prostate-specific membrane antigen.
The main goal of this study was to develop formulation parameters that would control the size of the resulting polymer nanoparticles, which the investigators believe play a major role in optimizing tumor targeting. The researchers prepared their nanoparticles from a poly(d,l-lactide-co-glycolide)-block-poly(ethylene glycol), a biocompatible material that the team had developed earlier. Experimenting with a variety of polymer concentrations and solvent mixtures, the researchers found for the first time that they could systematically control the size of the resulting polymers. The results were so consistent that the investigators believe that they may have developed a broadly applicable approach to reproducibly tuning the size of polymer nanoparticles during their formulation.
In a final experiment, the researchers added the targeting agent to their optimized nanoparticles. The targeted nanoparticles were able to significantly increase drug delivery to human prostate tumors growing in mice.
This work, which was supported by the National Cancer Institute, is detailed in a paper titled, “Formulation of functionalized PLGA-PEG nanoparticles for in vivo targeted drug delivery.” Investigators from the Massachusetts Institute of Technology and the Harvard Medical School also participated in this study. This paper was published online in advance of print publication. An abstract is available through PubMed.