Biocompatibility and resorption of intravenously administered polymer microparticles in tissues of internal organs of laboratory animals.
Specimens of (14)C-labeled polymer of 3-hydroxybutyric acid, P(3-HB), with different initial molecular weights, were used to prepare microparticles, whose morphology was not influenced by the M(w) of the polymer. During the particle preparation process, P(3-HB) molecular weight decreased by 15-20%. Sterile microparticles (mean diameter 2.4 μm) were injected into the tail veins of Wistar rats (5 mg/rat). The effects of the particles administered to rats were studied based on the general response of animals and local response of internal organ tissues and blood morphology; no adverse effects on growth and development of the animals or unfavorable changes in the structure of the tissues of internal organs were observed. Measurements of radioactivity in tissues showed that (14)C concentrations are different in different organs, changing during the course of the experiment. The main targets for (14)C-labeled microparticles were tissues of the liver, spleen, and kidneys. Comparison of radioactivity levels and residual contents of high-molecular-weight matrix in tissues suggested that the most rapid metabolism and degradation of P(3-HB) occurred in the liver and spleen. Gel-permeation chromatography showed that at 3 h after the microparticles were injected into the bloodstream, polymer degradation started in all examined organs, except the lungs; at 12 weeks, the M(w) of the polymer matrix was as low as 20-30% of its initial value. The presence of high-molecular-weight (undegraded) polymer in the tissues at 12 weeks after administration of the particles suggests that P(3-HB) is degraded in tissues of internal organs slowly and, hence, P(3-HB)-based microparticles can be used as sustained-release drug-delivery systems.
Institute of Biophysics SB RAS, Akademgorodok, Krasnoyarsk, Russia.
Ekaterina
E
Shishatskaya
Anastasiya
A
Goreva
Galina
G
Kalacheva
Tatiana
T
Volova
D000818:Animals; D000830:Animals, Laboratory / Q000033:anatomy & histology* / Q000378:metabolism*; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism*; D016503:Drug Delivery Systems; D005260:Female; D007262:Infusions, Intravenous; D008422:Materials Testing; D008863:Microspheres; D008970:Molecular Weight; D010316:Particle Size; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
D001672:Biocompatible Materials; D011108:Polymers