Biodegradable microspheres. XIII: Immune response to the DNP hapten conjugated to polyacryl starch microparticles.
Polyacryl starch microparticles are being investigated for use as drug carriers, especially in the treatment of intracellular parasitic diseases. The purpose of this work was to investigate the possible immune response to drugs coupled to the microparticles, using the dinitrophenyl group (DNP) as a model. The humoral immunogenicity of DNP hapten-conjugated polyacryl starch microparticles has been examined in mice. Microparticle:hapten complexes with different biodegradability were tested, as well as different dosages and routes of administration. Two DNP derivatives, Lys(DNP) and Leu-Ala-Lys(DNP), were coupled to microparticles. It was shown that Lys(DNP) was released from the particles by lysosomal enzymes only from the conjugate with the tripeptide DNP derivative. The DNP conjugated to the particles via the biodegradable Leu-Ala-Lys arm induced only a weak immune response without memory. No response was detected after injection of the Lys(DNP) microparticles. Thus, there should be no major immunological obstacles in using drug:microparticle complexes in the treatment of, for example, parasitic diseases.
Stjärnkvist
P
P
Department of Drugs, National Board of Health and Welfare, Uppsala, Sweden.
Degling
L
L
Sjöholm
I
I
D000276:Adjuvants, Immunologic; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D004140:Dinitrophenols / Q000737:chemistry / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006241:Haptens / Q000737:chemistry / Q000276:immunology*; D008247:Lysosomes / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D010047:Ovalbumin / Q000276:immunology; D010316:Particle Size; D012710:Serum Albumin, Bovine / Q000276:immunology; D013213:Starch / Q000031:analogs & derivatives* / Q000737:chemistry / Q000276:immunology
D000276:Adjuvants, Immunologic; D004140:Dinitrophenols; D006241:Haptens; D012710:Serum Albumin, Bovine; D013213:Starch; D010047:Ovalbumin; C043831:starch polyacrylate