Synthesis and Preliminary Evaluation of Novel Bone-targeting NSAIDs Prodrugs based on Glutamic Acid Oligopeptides
Osteoarthritis is no doubt a difficult disease to manage. Targeted delivery of drugs to bone
may not only enhance the treatment efficacy, but also reduces the quantity of drug administered. In
this paper, we have synthesized two series of NSAID-Glu oligopeptide conjugates built up by the
therapeutic moiety (naproxen and ibuprofen) and the targeting moieties (Glutamic oligopeptides) via
amide linkage, as novel potential bone-targeting NSAIDs prodrugs. Preliminary studies indicated that
these prodrugs exhibited outstanding hydroxyapatite affinity, furthermore, NSAIDs-glutamic hexa-peptide conjugates
were found more potent in hydroxyapatite binding. The adequate chemical stability of the conjugates in different buffers,
indicated that the conjugates might become a promising approach of selective delivery of drugs to bone tissues. These results
may be conducive to the study of bone targeting drugs delivery.
Keywords: Synthesis, bone-targeting, prodrug, NSAID, glutamic acid oligopeptide, Hydroxyapatite affinity.
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