Biodegradable polymeric microspheres and nanospheres for drug delivery in the peritoneum.
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.
Kohane
Daniel S
DS
Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. dkohane@partners.org
Tse
Julie Y
JY
Yeo
Yoon
Y
Padera
Robert
R
Shubina
Maria
M
Langer
Robert
R
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
D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid