The solubility of Mel in water was measured to be approximately
6–8 g/mL. Compared with the extremely poor solubility of Mel,
all of the tested conjugates showed satisfactory water solubility,
which was 160-fold (Mel-OCM-chitosan, 1.12 mg/mL) at least and
217-fold (Mel-Gly-OCM-chitosan-2, 1.52 mg/mL) at most of Mel (as
shown in Table 1). The solubility of the conjugates with same amino
acid spacer decreased with Mel substitution degree increased. The
conjugates showed good water solubility mainly due to the good
aqueous solubility of OCM-chitosan and the possibility of micellar
formation self-assembled by Mel-OCM-chitosan conjugates in the
aqueous solution. It was reported that hydrophobic modified OCMchitosan
can self-assemble into nanoparticles with a hydrophobic
core and a hydrophilic shell (Gong et al., 2012; Zheng, Han, et al.,
2011; Zheng, Rao, et al., 2011). The hydrophilic shell could increase
the water solubility of the prodrugs. In addition, the existence of
spacers also slightly enhanced the water solubility of the conjugates
although it showed no obvious regularity among different spacers.