ABSTRACT
@#Objective To evaluate the effects of various polysorbates(PS)on the stability of different types of monoclonal antibody(mAb)drugs.Methods Three types of monoclonal antibodies mAbA(IgG1 proantibody drug),mAbB(IgG1 mAb)and mAbC(IgG1 mAb with Fc N297A mutation)were used as model proteins,and different kinds or contents of PS were added into the mAb formulations respectively to investigate the influencing factors.The effects of PS on the stability of mAb drugs were evaluated comprehensively by detecting the changes of quality attributes,such as protein aggregates and insoluble particles.Results PS20 and PS80 showed no significant difference in inhibiting the formation of aggregates and charge variants in the three mAbs(P>0.05),while the addition of PS80 in mAbB and PS20 in mAbC significantly inhibited the increase of insoluble particles respectively(P<0.05);The content of PS20 showed a significant effect on the detection indexes of charge variants and insoluble particles in mAbC(P<0.05).Conclusion Different types of mAbs have different sensitivities to various kinds and contents of PS.Therefore,when designing the formulation of mAbs,it is necessary to select appropriate kinds and contents of PS to further improve the stability of mAb drugs.
ABSTRACT
The Ruanjian Sanjie Decoction (RSD) is a traditional Chinese medicine (TCM) formulation consisting of Spica Prunellae, Pseudobulbus Cremastrae Seu Pleiones, Concha Ostreae and Semen Coicis, and widely used as an adjuvant in anti-cancer therapy. The aim of this study was to determine the effects of RSD on the extracellular matrix (ECM) of tumors, and on the efficacy of anti-cancer nano-formulations in a tumor-bearing mouse model. The mice were treated with triptolide encapsulated in PEG-modified liposomes (TP-PEG-LPs), either alone or in combination with RSD. The combination treatment significantly retarded tumor growth relative to the untreated controls, indicating the potent adjuvant effect of RSD in targeted anti-cancer therapy. In addition, RSD also reduced the amount of total collagen and collagen I and increased that of collagen III in the tumor ECM, along with decreasing the expression of the pro-angiogenic VEGF. Finally, even high doses of RSD did not significantly affect the liver and kidney function or body weight, indicating low toxicity.