A polymeric hydrogel was found to significantly alter the equilibrium of the transformation between active and inactive forms of an anti-tumor drug

The Group found that some appropriate biomaterials can not only encapsulate drugs, but also alter the equilibrium of some drugs exhibiting transformation between active and inactive forms.

l        Enhancement of the fraction of the active form of an antitumor drug topotecan via an injectable hydrogel

Guangtao Chang, Tianyuan Ci, Lin Yu, Jiandong Ding*, J. Controlled Release, 156, 21-27 (2011)

Poly(D,L-lactic acid-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(D,L-lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) hydrogels were tried as implants to encapsulate antitumor drug topotecan (TPT), a derivative of camptothecin (CPT). Despite of water solubility of TPT, the in vitro release of this low-molecular-weight drug from hydrogels sustained for 5 days with only a mild initial burst. The antitumor efficacy of the released TPT was further validated in S180-bearing mice. Surprisingly, the fraction of the active lactone form of TPT was increased to above 50% in the hydrogel matrix, while the fraction was just about 10% in phosphate buffer saline under physiological pH at 37 °C. This significant effect was interpreted not by the local acidic pH within the hydrogel, but by the increase of pK_a of the carboxylate group of the open-ring form tedue to the hydrophobic interaction between the amphiphilic polymer and TPT. Theoretical analysis via a pK_a-related mechanism was also performed, which was consistent with our experimental measurements. Hence, this study has revealed that an appropriate biomaterial could, via drug-material interactions, enhance the drug efficacy by increasing the active fraction of some drugs which exhibit a reversible conversion between the active and inactive structures.

The interesting phenomenon was further interpreted by the pK_a shift of due to interaction between materials and drugs.