Biocompatibility and Resorption of Intravenously Administered Polymer Microparticles in Tissues of Internal Organs of Laboratory Animals


Тип публикации: статья из журнала

Год издания: 2011

Идентификатор DOI: 10.1163/092050610X537138

Ключевые слова: Resorbable polyhydroxybutyrate, microparticles, intravenous administration, (14)C products of polymer resorption, tissues of internal organs, 14C products of polymer resorption, 3-hydroxybutyric acid, <sup>14</sup>C products of polymer resorption, Adverse effect, Drug-delivery systems, Growth and development, High molecular weight, Initial molecular weight, Initial values, Internal organs, Laboratory animals, Local response, matrix, Mean diameter, Micro-particles, Polymer degradation, Polymer microparticles, Preparation process, Radioactivity level, Residual content, Resorbable, Sustained-release, Tail veins, Wistar rat, Animals, Biocompatibility, Degradation, Histology, Molecular weight, Morphology, Radiation, Radioactivity, Rats, Tissue, poly(3 hydroxybutyric acid), animal experiment, animal tissue, article, concentration process, controlled study, drug delivery system, female, gel permeation chromatography, heart, kidney parenchyma, liver, lung parenchyma, nonhuman, organ culture, priority journal, rat, spleen, Animals, Laboratory, Biocompatible Materials, Drug Delivery Systems, Infusions, Intravenous, Materials Testing, Microspheres, Particle Size, Polymers, Rats, Wistar, Tissue Distribution, Animalia, Rattus, Rattus norvegicus

Аннотация: 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 diamПоказать полностьюeter 2.4 mu m) 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 Mw 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. (C) Koninklijke Brill NV, Leiden, 2011

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Выпуск журнала: Vol. 22, Is. 16

Номера страниц: 2185-2203

ISSN журнала: 09205063

Место издания: LEIDEN

Издатель: VSP BV