title: Long-circulation of hemoglobin-loaded polymeric nanoparticles as oxygen carriers with modulated surface charges.
abstract: The aim of this study was to investigate the effects of the surface charges on the in vitro macrophage cellular uptake and in vivo blood clearance and biodistribution of the hemoglobin-loaded polymeric nanoparticles (HbPNPs). The surface charges of the HbPNPs fabricated from mPEG-PLA-mPEG were modulated with cationized cetyltrimethylammonium bromide (CTAB) and anionized sodium dodecyl sulphate (SDS), respectively. In vitro macrophage cellular uptake and in vivo biodistribution of the coumarin 6-labeled HbPNPs with different electric charges were investigated, and the half-lives in the circulation were pharmacokinetically analyzed. The particle sizes of the HbPNPs were all below 200 nm with a narrow size distribution and high encapsulation efficiency (>84%). And the zeta-potentials of the untreated, cationized and anionized HbPNPs in phosphate buffered sodium chloride solution (PBS) were -12.3, +3.28 and -25.4 mV, respectively. The HbPNPs did not occur significant aggregation or sedimentation, even after 5 days. Compared with the untreated HbPNPs, 1-fold decrease/increase of the uptake percentage associated with the cationized/anionized HbPNPs was observed. In vivo experiment demonstrated that the calculated half-life of the cationized HbPNPs was 10.991 h, 8-fold longer than that of the untreated HbPNPs (1.198 h). But the anionized HbPNPs displayed opposite effect. Furthermore, the cationized HbPNPs mainly accumulated in the liver, lung and spleen after 48 h injection. MTT results showed that the HbPNPs with different surface charges all exhibited slight toxicity. These results demonstrated that the CTAB-modulated HbPNPs with low positive charge and suitable size have a promising potential as a long-circulating oxygen carrier system with desirable biocompatibility and biofunctionality.
authors.affiliation: Key Laboratory for Ultrafine Materials of Ministry of Education, and Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, PR China.
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Shan
authors.forename: Changsheng
authors.initials: C
authors.lastname: Liu
authors.forename: Xinyi
authors.initials: X
authors.lastname: Tao
authors.forename: Yan
authors.initials: Y
authors.lastname: Sheng
authors.forename: Huanjun
authors.initials: H
authors.lastname: Zhou
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004337:Drug Carriers / Q000493:pharmacokinetics / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods; D004355:Drug Stability; D006454:Hemoglobins / Q000008:administration & dosage / Q000493:pharmacokinetics; D017737:Macrophages, Peritoneal / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010100:Oxygen / Q000008:administration & dosage*; D010316:Particle Size; D011108:Polymers / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D004337:Drug Carriers; D006454:Hemoglobins; D011108:Polymers; D010100:Oxygen