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Acrylic microspheres in vivo VIII: distribution and elimination of polyacryldextran particles in mice
Abstract:
The disposition of different 14C-labeled, biodegradable polyacryldextran microparticles after intravenous injection has been studied in the mouse. The particles were rapidly cleared from the circulatory system by the reticuloendothelial system. They were predominantly (60-80%) found in the liver and spleen and to some extent in the bone marrow. Large particle aggregates were found in the lungs 6 hr postinjection. After redistribution, the particles were eliminated from the organs with an apparent t 1/2 of 12-30 weeks, depending on the composition of the particles. Highly cross-linked particles with 2% acrylic groups (DTC = 11-2-75) had a half-life similar to that of polyacrylamide particles (TC = 8-25). The metabolism rate was also correlated with the degradation in vitro with isolated rat lysosomes. After intravenous injection of small 14C-labeled polyacrylamide particles (0.2-0.5 micron), significant amounts of radioactivity were detected in the bile and gallbladder.
Insights
Biodegradable polyacryldextran microparticles are rapidly cleared by the reticuloendothelial system, accumulating in the liver and spleen. Organ elimination occurs over 12-30 weeks, influenced by particle composition and cross-linking.
Area of Science:
- Biomaterials Science
- Pharmacokinetics
- Nanotechnology
Background:
- Biodegradable microparticles are investigated for drug delivery and biomedical applications.
- Understanding the in vivo fate of injected microparticles is crucial for safety and efficacy.
- Polyacryldextran microparticles offer tunable properties for potential therapeutic uses.
Purpose of the Study:
- To investigate the in vivo disposition and clearance of 14C-labeled polyacryldextran microparticles after intravenous administration in mice.
- To determine the influence of particle composition and cross-linking on microparticle biodistribution and elimination half-life.
- To correlate in vivo degradation rates with in vitro lysosomal degradation.
Main Methods:
- Intravenous injection of 14C-labeled polyacryldextran microparticles into mice.
- Quantification of radioactivity in major organs (liver, spleen, lungs, bone marrow) and excreta over time.
- Analysis of particle aggregation in lung tissue at specific time points.
- In vitro degradation studies using isolated rat lysosomes.
Main Results:
- Rapid clearance of microparticles from circulation by the reticuloendothelial system.
- Predominant accumulation (60-80%) in the liver and spleen, with some in bone marrow.
- Detection of large particle aggregates in lungs 6 hours post-injection.
- Organ elimination half-life ranged from 12 to 30 weeks, dependent on particle composition.
- Highly cross-linked particles exhibited half-lives similar to polyacrylamide particles.
- Radioactivity detected in bile and gallbladder following injection of small polyacrylamide particles.
Conclusions:
- Polyacryldextran microparticles are primarily cleared by the reticuloendothelial system and accumulate in the liver and spleen.
- Particle degradation and elimination rates are influenced by cross-linking and composition, correlating with in vitro lysosomal degradation.
- The study provides insights into the pharmacokinetic profile of biodegradable polyacryldextran microparticles, informing future biomaterial design.