title: Biodegradable polymeric microspheres and nanospheres for drug delivery in the peritoneum.
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 microm 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-microm microparticles caused adhesions in 83% of animals). Histology revealed chronic inflammation, with foreign body giant cells prominent with particles>5 microm 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.
authors.affiliation: Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. dkohane@partners.org
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Kohane
authors.forename: Julie Y
authors.initials: JY
authors.lastname: Tse
authors.forename: Yoon
authors.initials: Y
authors.lastname: Yeo
authors.forename: Robert
authors.initials: R
authors.lastname: Padera
authors.forename: Maria
authors.initials: M
authors.lastname: Shubina
authors.forename: Robert
authors.initials: R
authors.lastname: Langer
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism*; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008422:Materials Testing; D051379:Mice; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D008970:Molecular Weight; D010316:Particle Size; D010537:Peritoneum / Q000033:anatomy & histology / Q000378:metabolism; D011100:Polyglycolic Acid / Q000737:chemistry / Q000378:metabolism*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry / Q000378:metabolism*; D013242:Sterilization / Q000379:methods
chemical_list: D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid