An investigation of the structure and drug release mechanism of a drug delivery system is proposed on the basis of semi-empirical and ab initio computations in vacuum stage. Cis-aconityl linkage is used to improve the interaction between an anti-cancer agent, doxorubicin, and a glycol chitosan biopolymer. It has been found that the doxorubicin-conjugated glycol chitosan carrier has more stability. The stability is increased when the lengths of the polyethylene glycol (PEG) chains in the glycol chitosan biopolymer are increased. Cis-aconityl can release doxorubicin under appropriate environmental conditions. Relative energies of this mechanism in an acid condition, as determined by B3LYP/6-31G//PM3, are 122.41, 119.27, 160.18 and 222.22 kcal/mol, and by the B3LYP/6-31G//HF/6-31G method are 54.23, 109.28, 219.98 and 980.49 kcal/mol, with mono-, di-, tri-, and quanta-ethylene glycol, respectively. In a normal condition, the relative energies are above 300 kcal/mol for all reactions. Therefore, cis-aconityl will release doxorubicin in an acid solution but not in a normal condition. The glycol chitosan polymer can be degraded in an acid solution as well. Long PEG chains influence the release mechanism of doxorubicin. The proposed length of the PEG chain is di-ethylene glycol. These simulation results agree well with various reported experimental data.