Biodegradable polymeric microspheres and nanospheres for drug delivery in the peritoneum Export

@article{citeulike:2363922, abstract = {Drug delivery to the peritoneum is hampered by rapid clearance, and could be improved by application of controlled release technology. We investigated the suitability for peritoneal use of micro- and nanoparticles of poly(lactic-co-glycolic) acid (PLGA), a biodegradable polymer with generally excellent biocompatibility commonly used for controlled drug release. We injected 90 kDa PLGA microparticles, 5-250 ?m in diameter, into the murine peritoneum, in dosages of 10-100 mg (n = 3-5 per group). We found a high incidence of polymeric residue and adhesions 2 weeks after injection (e.g., 50 mg of 5-?m microparticles caused adhesions in 83\% of animals). Histology revealed chronic inflammation, with foreign body giant cells prominent with particles \>5 ?m in diameter. Five micrometer microspheres made from 54, 57, and 10 kDa PLGA (gamma irradiated) caused fewer adhesions (16.7\%) with a similar incidence of residue. Nanoparticles (265 nm) of 90 kDa PLGA also caused much fewer adhesions (6.3\% of animals), possibly because they were cleared from the peritoneum within 2 days, and sequestered in the spleen and liver, where foamy macrophages were noted. The effect of sterilization technique on the incidence of adhesion formation is also studied. {\copyright} 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006}, address = {Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts; Harvard-MIT Division of Health Sciences and Technology, Cambridge, Massachusetts; Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts; Harvard School of Public Health, Boston, Massachusetts}, author = {Kohane, Daniel S. and Tse, Julie Y. and Yeo, Yoon and Padera, Robert and Shubina, Maria and Langer, Robert}, citeulike-article-id = {2363922}, citeulike-linkout-0 = {http://dx.doi.org/10.1002/jbm.a.30654}, citeulike-linkout-1 = {http://www3.interscience.wiley.com/cgi-bin/abstract/112276100/ABSTRACT}, doi = {10.1002/jbm.a.30654}, journal = {Journal of Biomedical Materials Research Part A}, keywords = {adhesion, aggregation, intraperitoneal-injection, mit-mgh-ccne, murine-model, phagocytosis, plga-microspheres, plga-nanospheres, polylactic-co-glycolic-acid}, number = {2}, pages = {351--361}, posted-at = {2008-02-11 22:20:38}, priority = {0}, title = {Biodegradable polymeric microspheres and nanospheres for drug delivery in the peritoneum}, url = {http://dx.doi.org/10.1002/jbm.a.30654}, volume = {77A}, year = {2006} }

TY - JOUR ID - citeulike:2363922 L3 - citeulike-article-id:2363922 N2 - Drug delivery to the peritoneum is hampered by rapid clearance, and could be improved by application of controlled release technology. We investigated the suitability for peritoneal use of micro- and nanoparticles of poly(lactic-co-glycolic) acid (PLGA), a biodegradable polymer with generally excellent biocompatibility commonly used for controlled drug release. We injected 90 kDa PLGA microparticles, 5-250 ?m in diameter, into the murine peritoneum, in dosages of 10-100 mg (n = 3-5 per group). We found a high incidence of polymeric residue and adhesions 2 weeks after injection (e.g., 50 mg of 5-?m microparticles caused adhesions in 83% of animals). Histology revealed chronic inflammation, with foreign body giant cells prominent with particles >5 ?m in diameter. Five micrometer microspheres made from 54, 57, and 10 kDa PLGA (gamma irradiated) caused fewer adhesions (16.7%) with a similar incidence of residue. Nanoparticles (265 nm) of 90 kDa PLGA also caused much fewer adhesions (6.3% of animals), possibly because they were cleared from the peritoneum within 2 days, and sequestered in the spleen and liver, where foamy macrophages were noted. The effect of sterilization technique on the incidence of adhesion formation is also studied. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006 IS - 2 JF - Journal of Biomedical Materials Research Part A AD - Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts; Harvard-MIT Division of Health Sciences and Technology, Cambridge, Massachusetts; Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts; Harvard School of Public Health, Boston, Massachusetts EP - 361 TI - Biodegradable polymeric microspheres and nanospheres for drug delivery in the peritoneum VL - 77A SP - 351 KW - adhesion KW - aggregation KW - intraperitoneal-injection KW - mit-mgh-ccne KW - murine-model KW - phagocytosis KW - plga-microspheres KW - plga-nanospheres KW - polylactic-co-glycolic-acid AU - Kohane, Daniel AU - Tse, Julie AU - Yeo, Yoon AU - Padera, Robert AU - Shubina, Maria AU - Langer, Robert PY - 2006/// UR - http://dx.doi.org/10.1002/jbm.a.30654 ER -