Thirdly, connecting Mel and OCM-chitosan molecules with
amide bond directly, displayed the highest stability toward both
chemical and enzymatic hydrolysis. In contrast, conjugates with
amino acid spacers showed relative fast and increased drug
release velocity, which means that these conjugates have enzymeresponsive
characteristic, and enzymatic release of melphalan from
Mel-OCM-chitosan conjugates was clearly dependent on the amino
acid used to link drug to polymer. In all cases, the rate of release was
as follows: Mel-Gly-OCM-chitosan > Mel-Pro-OCM-chitosan > Mel-
Phe-OCM-chitosan > Mel-Leu-OCM-chitosan. The results demonstrated
that increased steric hindrance provided by spacers with
large side chain could lead to a lower and slower free drug release
under the same environmental condition. This can be attributed
that the large side chain induced steric hindrance would become
an obstacle for the enzymatic hydrolysis