Spray-dried lipid-hyaluronan-polymethacrylate microparticles for drug delivery in the peritoneum.
Application of controlled release technology to the peritoneum would allow for sustained drug levels. However, some polymeric systems either create adhesions, or rapidly exit the peritoneum; neither result is desirable. Here we have produced particles based on sphyngomyelin, a phospholipid that occurs naturally in the peritoneum, along with hyaluronic acid and the polymethacrylate Eudragit E100 (to modulate drug release). Particles with a low proportion of E100 (5% (w/w); "high SPM") release albumin rapidly over 2 days, then more slowly; increasing the E100 to 20% (w/w; high "E100") slowed drug release markedly. When injected in the murine peritoneum, high SPM particles were disseminated as free particles, without forming collections. There was a mild inflammatory response but no formation of adhesions. High E100 particles formed collections in all animals, with an intense inflammatory response. Even so, there were very few adhesions. These results suggest that microparticulate formulations can be produced that have acceptable drug-releasing properties and are suitable for use in the peritoneum from the standpoint of biocompatibility.
Domnina
Yuliya A
YA
Division of Pediatric Critical Care, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
Yeo
Yoon
Y
Tse
Julie Y
JY
Bellas
Evangelia
E
Kohane
Daniel S
DS
D000179:Acrylates / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000418:Albumins / Q000008:administration & dosage / Q000493:pharmacokinetics; D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000493:pharmacokinetics; D004337:Drug Carriers; D005079:Excipients / Q000008:administration & dosage / Q000493:pharmacokinetics; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010537:Peritoneum / Q000187:drug effects*; D011108:Polymers / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011109:Polymethacrylic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013109:Sphingomyelins / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000179:Acrylates; D000418:Albumins; D001672:Biocompatible Materials; D004337:Drug Carriers; C477020:Eudragit E100; D005079:Excipients; D011108:Polymers; D011109:Polymethacrylic Acids; D013109:Sphingomyelins; C030613:polymethacrylic acid; D006820:Hyaluronic Acid