Recently, a great effort has been made to perfect the therapeutic effect of solid tumor, from single-agent therapy to combined therapy and many other polymer-drug conjugations with dual or more anticancer agents due to their promising synergistic effect and higher drug level accumulation towards tumor tissues. Different polymer-drug spacers present diverse therapeutic efficacy, therefore, finding an appropriate spacer is desirable. In this study, dual drugs that are doxorubicin (DOX) and mitomycin C (MMC) were conjugated onto a polymer carrier (xyloglucan) via various peptide or amide bonds, and a series of polymers drug conjugates were synthesized with different spacers and their effect on tumor treatment efficacy was studied both in vitro and in vivo. The result shows that the synergistic effect is better when using different linker to conjugate different drugs rather than using the same spacer to conjugate different drugs on the carrier. Particularly, the finding of this works suggested that, using peptide bond for MMC and amide bond for DOX to conjugate dual drugs onto single XG carrier could improve therapeutic effect and synergy effect. Therefore, in polymer-pharmaceutical formulations, the use of different spacers to optimize the design of existing drugs to enhance therapeutic effects is a promising strategy.

Progesterone injection is oily because of its poor solubility. It is necessary to develop new dosage forms or delivery methods for Progesterone. Six cocrystals of Progesterone with nitrogen heterocyclic compounds (2,6-diaminopyridine, isonicotinamide, 4-aminopyridine, aminopyrazine, picolinamide and pyrazinamide) have been designed and prepared by ethyl acetate-assisted grinding, of which four cocrystals (2,6-diaminopyridine, isonicotinamide, 4-aminopyridine and aminopyrazine) had single crystal data in 1:1 stoichiometry. Metadynamics-genetic crossing was used to search and optimize various cluster structures to explain the reason the other two cocrystals could not be obtained with suitable size for single crystal X-ray diffraction. In contrast to the carboxyl group, the amide group and amino group were good substituents in the pyridine/pyrazine ring for cocrystallization with Progesterone, which meant inductive effect played an important role in nitrogen heterocyclic compounds containing reactive hydrogen. All cocrystals were more soluble than Progesterone in water, and Progesterone–pyrazinamide cocystal featured the best water solubility performance with an approximately six-fold increase over free Progesterone. This successful attempt provides an effective route for designing and manufacturing novel solid states of Progesterone.