Targeted delivery of pixantrone to neutrophils by poly(sialic acid)-p-octadecylamine conjugate modified liposomes with improved antitumor activity

Publication date: 25 August 2018Source: International Journal of Pharmaceutics, Volume 547, Issues 1–2Author(s): Xiang Luo, Mingqi Liu, Ling Hu, Qiujun Qiu, Xinrong Liu, Cong Li, Mei Lu, Yang Liu, Ting Zhang, Songlei Zhou, David Julian McClements, Xian Jia, Yihui Deng, Yanzhi SongAbstractBased on the knowledge that poly(sialic acid) is a critical element for tumour development and that the receptors for its monomer are expressed on neutrophils, which play important roles in the progression and invasion of tumours, a poly(sialic acid)-p-octadecylamine conjugate (PSA-p-ODA) was synthesised and used to modify the surface of liposomal pixantrone (Pix-PSL) to improve the delivery of Pix to peripheral blood neutrophils (PBNs). The liposomes were fabricated using a remote loading technology via a pH gradient, and were then assessed for particle size, encapsulation efficiency, in vitro release, in vitro cytotoxicity, and pharmacokinetics. Simultaneously, in vitro and in vivo cellular uptake studies demonstrated that Pix-PSL provided an enhanced accumulation of Pix in PBNs. An in vivo study showed that the anti-tumour activity of Pix-PSL was superior to that of other formulations, probably owing to the efficient targeting of PBNs by Pix-PSL, after which PBNs containing Pix-PSL (Pix-PSL/PBNs) in the circulatory system are recruited by the tumour microenvironment. These findings suggest that PSA-p-ODA-decorated liposomal Pix may provide a neutrophil-mediated drug delivery system (DDS)...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research