Characterization of nanoparticle-mediated drug delivery to NB4: Feasibility of nanoparticle use for cells in suspension and blood diseases

Acute promyelocytic leukemia (APL), a subtype of acute myeloid leukemia, is characterized by t(15;17) reciprocal chromosomal translocation resulting in the formation of a chimeric promyelocytic leukemia/retinoic acid receptor-alpha(PML/RARα) fusion protein. PML/RARα fusion protein blocks myeloid differentiation and suppresses apoptosis resulting in clinical expression of cells in a promyelocytic stage. A primary treatment option for patients suffering from APL is the use of the drug all-trans-retinoic acid (RA), a derivative of vitamin A. RA induces differentiation in various cancers including APL. The chemical properties of RA lead to limited treatment options and frequently lead to drug resistance and disease relapse. Using a nano-dispersion technique we encapsulated RA in poly(D,L-lactide-co-glycolide) nanoparticles for sustained intracellular release of the drug and enhanced cellular uptake. The formulation technology successfully encapsulates 90% of the drug, generating nanoparticles in a size range from 61-578 nm. RA release from nanoparticles follows classical small molecule dynamics and our results show rapid uptake of the particles by NB4 cells, an APL cell line. Further, using a concentration of 1 mg/mL of RA loaded nanoparticles we are able to observe differentiation at approximately 3-4 fold less than the required 1 μM dose of free RA. Our data indicate that the properties of these nanoparticles may provide one potential clinical use as a treatment option for APL.