Purpose: In this study, pH-sensitive poly(2-ethyl-2-oxazoline)-poly(lactic acid)-poly(β-amino ester) (PEOz-PLA-PBAE) triblock copolymers were synthesized and were conjugated with an antimalaria drug artesunate (ART), for inhibition of a colon cancer xenograft model. Methods: The as-prepared polymer prodrugs are tended to self-assemble into polymeric micelles in aqueous milieu, with PEOz segment as hydrophilic shell and PLA-PBAE segment as hydrophobic core. Results: The pH sensitivity of the as-prepared copolymers was confirmed by acid-base titration with pKb values around 6.5. The drug-conjugated polymer micelles showed high stability for at least 96 h in PBS and 37°C, respectively. The as-prepared copolymer prodrugs showed high drug loading content, with 9.57%± 1.24% of drug loading for PEOz-PLA-PBAE-ART4. The conjugated ART could be released in a sustained and pH-dependent manner, with 92% of released drug at pH 6.0 and 57% of drug released at pH 7.4, respectively. In addition, in vitro experiments showed higher inhibitory effect of the prodrugs on rodent CT-26 cells than that of free ART. Animal studies also demonstrated the enhanced inhibitory efficacy of PEOz-PLA-PBAE-ART2 micelles on the growth of rodent xenograft tumor. Conclusion: The pH-responsive artesunate polymer prodrugs are promising candidates for colon cancer adjuvant therapy.

Acute lung injury (ALI) or its aggravated stage acute respiratory distress syndrome (ARDS) is a common severe clinical syndrome in intensive care unit, may lead to a life-threatening form of respiratory failure, resulting in high mortality up to 30–40% in most studies. Nanotechnology-mediated anti-inflammatory therapy is an emerging novel strategy for the treatment of ALI, has been demonstrated with unique advantages in solving the dilemma of ALI drug therapy. Artesunate (ART), a derivative of artemisinin, has been reported to have anti-inflammatory effects. Therefore, in the present study, we designed and synthesized PEGylated ART prodrugs and assessed whether ART prodrugs could attenuate lipopolysaccharide (LPS) induced ALI in vitro and in vivo. All treatment groups were conditioned with ART prodrugs 1 h before challenge with LPS. Significant increased inflammatory cytokines production and decreased GSH levels were observed in the LPS stimulated mouse macrophage cell line RAW264.7. Lung histopathological changes, lung W/D ratio, MPO activity and total neutrophil counts were increased in the LPS-induced murine model of ALI via nasal administration. However, these results can be reversed to some extent by treatment of ART prodrugs. The effectiveness of mPEG_2k-SS-ART in inhibition of ALI induced by LPS was confirmed. In conclusion, our results demonstrated that the ART prodrugs could attenuate LPS-induced ALI effectively, and mPEG_2k-SS-ART may serve as a novel strategy for treatment of inflammation induced lung injury.

A pH sensitive micellar cargo was fabricated for pH triggered delivery of hydrophobic drug paclitaxel with pH controlled drug release profiles. The size, drug loading content, and encapsulation efficiency of PTX loaded micelles were 20–30 nm, 7.5%, 82.5%, respectively. PTX loaded PELA-PBAE micelles could enhance the intracellular uptake of a model drug significantly, with increased cytotoxicity and inhibition of tumor metastasis on 4T1 cells, as confirmed by wound healing assay and tumor cells invasion assay. The expression of metastasis and apoptosis correlated proteins on 4T1 cells decreased remarkably after intervention by PTX loaded polymer micelles, as demonstrated by western blotting and quantitative reverse transcriptional-polymerase chain reaction (qRT-PCR). Our results demonstrated the pH responsive polymer micelles might have the potential to be used in the treatment of metastatic breast tumors.