In-house glutamine based compound loaded poly-(D-L-lactide-coglycolide) nanoparticles as a possible candidate for the management of chronic myeloid leukemia

Abstract

The development of targeted medicines such tyrosine kinase inhibitors (TKIs) have turned chronic myeloid leukemia (CML) from a potentially fatal illness into a manageable chronic condition for many individuals. But in case of TKIs, some serious drug induced adverse events as well as drug resistance were reported. In continuation of our earlier work, we have synthesized two p-nitrobenzenesulfonyl-D-glutamine derivatives which were screened against human CML cell line (K562). In comparison with earlier reported p-nitrobenzenesulfonyl-L-glutamine derivatives (Compound 1 and Compound 2), newly synthesized compounds showed more than 3 times better activity against K562 cell line. The best active compound (Compound 3) was encapsulated into Poly-(D-L-lactide-coglycolide) nanoparticles (NPs). The NPs were characterized and screened against K562 and human PBMC cell line. The IC50 value of NP of Compound 3 was found in the nanomolar range (522 nM) against K562 cell line which is more than 10 times better active than Compound 3. DNA deformation assay also indicates cell shrinkage and nuclear fragmentation which are associated with apoptosis-mediated cell death. The prepared NPs of Compound 3 (NP3) are very much less toxic against normal human PBMC (IC50 value > 500 µM). The current study implies that NP3 holds promise for managing chronic myeloid leukemia.