title: Effect of thiol functionalization on the hemo-compatibility of PLGA nanoparticles.
abstract: In this study, an attempt was made to reduce the interaction of poly(D,L-lactic acid/glycolic acid) (PLGA) nanoparticles with the opsonins and phagocytic cells upon functionalization with thiol groups. Terminal carboxylic groups in PLGA were conjugated to the amino group of cysteine and nanoparticles were prepared by solvent evaporation technique. Detailed in vitro investigations were performed on PLGA and cysteine modified PLGA (Cys-PLGA) nanoparticles to asses their blood compatibility. The effect of these nanoparticles on the release of proinflammatory cytokines (IL-1β, IL-6, and TNF-α) from human macrophage cells were evaluated. Thiolation was confirmed by fourier transform infrared spectroscopy and Ellman's assay; both PLGA and modified nanoparticles had average size in the range of 250 nm. Thiolation was an effective strategy in reducing the protein adsorption, complement activation, and platelet activation of PLGA nanoparticles. PLGA and modified PLGA nanoparticles were compatible with the blood cells and no hemolytic effect was detected. Particles were noncytotoxic on L929 cells and release of proinflammatory cytokines from macrophage cells was rather unaffected with the modification strategy. From these studies, it seems that thiolation of particulate delivery system is an interesting approach in manipulating the blood-particle interactions and appears to be an effective candidate for injectable drug delivery applications.
authors.affiliation: Division of Biosurface Technology, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences & Technology, Thiruvananthapuram 695012, India.
authors.forename: Y M
authors.initials: YM
authors.lastname: Thasneem
authors.forename: S
authors.initials: S
authors.lastname: Sajeesh
authors.forename: Chandra P
authors.initials: CP
authors.lastname: Sharma
mesh_terms: D000327:Adsorption; D001672:Biocompatible Materials / Q000737:chemistry* / Q000378:metabolism*; D002448:Cell Adhesion; D002460:Cell Line; D003167:Complement Activation; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods; D006461:Hemolysis; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D019344:Lactic Acid / Q000737:chemistry* / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D008422:Materials Testing; D053758:Nanoparticles / Q000737:chemistry*; D015539:Platelet Activation; D011100:Polyglycolic Acid / Q000737:chemistry* / Q000378:metabolism*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D017550:Spectroscopy, Fourier Transform Infrared; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; D004337:Drug Carriers; D053583:Interleukin-1beta; D015850:Interleukin-6; D013438:Sulfhydryl Compounds; D014409:Tumor Necrosis Factor-alpha; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid