title: Safe and efficient pH sensitive tumor targeting modified liposomes with minimal cytotoxicity.
abstract: Incorporating the pH-sensitivity of octylamine grafted poly aspartic acid (PASP) with the biocompatibility of liposomes, a novel pH sensitive drug delivery system, octylamine-graft-PASP (PASP-g-C8) modified liposomes (OPLPs), was obtained. Since hydrophobic chains have been grafted into PASP backbones, the octylamine chain could act as the "anchor" to implant onto liposomes. The structure of PASP-g-C8, involving long-chain and hydrophobic anchors can significantly enhance the stability of the drug carrier. The shortcoming of single PASP chain modified liposomes (PLPs), that cannot sustain a slow and controlled release especially in a physiological pH solution (resembling normal tissues of pH 7.4) is thus overcome. Drug release experiments were carried out and the result showed that OPLPs sustained a slow and steady release in comparison with PLPs in the physiological pH 7.4 environment. However, OPLPs can provide a fast release in subacid environment (pH 5.0 of resembled tumor tissues). The results of diameter analysis and zeta potential demonstrated that OPLPs presented a larger diameter and higher electronegativity. Furthermore, in the "chain-anchor" structure of PASP-g-C8, the degree of substitution (DS) of the "anchor" is a remarkable factor to alter the pH-sensitivity of OPLPs. The in vitro tumor inhibition and cell toxicity studies revealed that tumor cells treated with OPLPs survived only 35.0% after 48 h whereas normal cells survived 100% in the same condition. The pH sensitive OPLPs are promising tumor targeting drug delivery with high tumor inhibition and insignificant cytotoxicity.
authors.affiliation: State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, 15 Beisanhuan East Road, Chaoyang District, Beijing, China.
authors.forename: Lilin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Beijing University of Chinese Medicine, 11 Beisanhuan East Road, Chaoyang District, Beijing, China.
authors.forename: Di
authors.initials: D
authors.lastname: Geng
authors.affiliation: State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, 15 Beisanhuan East Road, Chaoyang District, Beijing, China. Electronic address: suhj@mail.buct.edu.cn.
authors.forename: Haijia
authors.initials: H
authors.lastname: Su
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000009:adverse effects / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000009:adverse effects / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy*
chemical_list: D004337:Drug Carriers; D008081:Liposomes
keywords: Efficient and safe drug carrier; Liposomes; Poly aspartic acid; Tumor targeting; pH sensitivity