Exhausting tumor associated macrophages with sialic acid-polyethyleneimine-cholesterol modified liposomal doxorubicin for enhancing sarcoma chemotherapy

Publication date: Available online 14 January 2019Source: International Journal of PharmaceuticsAuthor(s): Huangliang Zheng, Jiaqi Li, Mengjing Wang, Xiang Luo, Qiujun Qiu, Ling Hu, Cong LI, Yanzhi Song, Yihui DengAbstractTo overstep the dilemma of chemical drug degradation within powerful lysosomes of tumor associated macrophages (TAMs), a sialic acid-polyethylenimine-cholesterol (SA-PEI-CH) modified liposomal doxorubicin (DOX-SPCL) was designed with both TAMs targeting and smart lysosomal trafficking. The modified liposome DOX-SPCL performed particle size as 103.2 ± 3.1 nm and zeta potential as -4.5 ± 0.9 mV with encapsulation efficiency as 95.8 ± 0.5%. In in vitro cell experiments, compared with conventional liposomal doxorubicin (DOX-CL) and PEGylated liposomal doxorubicin (DOX-PL), DOX-SPCL showed a selective binding on TAMs and a mere lysosomal concentration. In pharmacokinetic study, DOX-SPCL effectively impeded/delayed the disposition of mononuclear phagocyte system (MPS) with a value of AUC0-t as 796.03 ± 66.93 mg L-1 h. In S180 sarcomas bearing mice, DOX-SPCL showed the greatest tumor inhibition rate (92.7 % ± 3.6 %) compared with DOX-CL (46.4 % ± 2.0 %) or DOX-PL (58.8 % ± 7.6 %). The < 0.5 % positive region of TAMs in tumor section indicated a super TAMs exhaustion for DOX-SPCL treatment. Conclusively, DOX-SPCL was supposed as a safe and effective liposomal preparation for clinical sarcoma treatment via TAMs targeting/deletion delivery strategy.Graphica...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research