Here, a biodegradable polymer-drug conjugate of doxorubicin (DOX) conjugated with a stearic acid-grafted chitosan oligosaccharide (CSO-SA) was synthesized via disulfide linkers. The obtained polymer-drug conjugate DOX-SS-CSO-SA could self-assemble into nanosized micelles in aqueous medium with a low critical micelle concentration. The size of the micelles was 62.8 nm with a narrow size distribution. In reducing environments, the DOX-SS-CSO-SA could rapidly disassemble result from the cleavage of the disulfide linkers and release the DOX. DOX-SS-CSO-SA had high efficiency for cellular uptake and rapidly released DOX in reductive intracellular environments. In vitro antitumor activity tests showed that the DOX-SS-CSO-SA had higher cytotoxicity against DOX-resistant cells than free DOX, with reversal ability up to 34.8-fold. DOX-SS-CSO-SA altered the drug distribution in vivo, which showed selectively accumulation in tumor and reduced nonspecific accumulation in hearts. In vivo antitumor studies demonstrated that DOX-SS-CSO-SA showed efficient suppression on tumor growth and relieved the DOX-induced cardiac injury. Therefore, DOX-SS-CSO-SA is a potential drug delivery system for safe and effective cancer therapy.
The geometrical parameters of annular centrifugal contactors (ACCs) have an important influence on the extraction efficiency. The present work used a home-made 25 mm ACC constructed by 3D printing to investigate the effect of five geometrical parameters on the extraction efficiency. These parameters are annular width (d), clearance height (Hc), rotor inlet diameter (Din), bottom vane number (N), and the bottom vane’s bending direction (S). Central composite design was employed to design the experiment, and the response surface methodology was used to analyze the data. The results show that Hc and Din were positive for efficiency, while d and N were negative. When the bottom vane’s bending direction was the same as the liquid helical flow direction, the efficiency improved compared to the straight vane. It is found that 3 mm d, 5 mm Hc, 6 mm Din, and four clockwise covered vanes are the parameters where the efficiency reached the highest point of 94.5%. We analyzed the interactions between the parameters based on the coefficients of the quadratic equation, and the interactions were not considered in previous studies. This work surprisingly reveals that the effects of the parameters on the extraction efficiency were not independent, and there were interactions between the parameters. The interaction between the rotor inlet diameter and annular width was significant and could not be ignored. These results could serve as a reference for optimizing extraction processes and the design of ACCs.
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