Degradation of porous poly(anhydride-co-imide) microspheres and implications for controlled macromolecule delivery.
The degradation properties of porous microspheres made using a new family of polyanhydride copolymers, the poly(anhydride-co-imides), were studied. Poly[trimellitylimido-L-tyrosine-co-sebacic acid-co-1,3-bis(carboxyphenoxy)propane] microspheres, with and without entrapped bovine serum albumin (BSA) as a model protein, were made using the double emulsion solvent evaporation process. Water penetration and anhydride bond cleavage (polymer degradation) occurred rapidly (< 5 days) compared to the time scale of overall microsphere erosion (weeks to months) with most polymer compositions. Subsequent to bond cleavage, the ultimate erosion of the microsphere and release of entrapped BSA was due mainly to the slow dissolution of the individual hydrophobic monomers (TMA-Tyr, SA and CPP) from the microsphere surface. BSA was released at approximately the same rate as the polymer eroded. Due to the fast degradation of anhydride bonds relative to microsphere erosion, initial polymer molecular weight did not have a significant effect on macromolecule release rates. Instead, monomer solubility correlated well with polymer erosion and BSA release rates. This erosion mechanism leads to predictable drug release rates which may be appropriate for the delivery of many protein therapeutics, including vaccine antigens. The anhydride-imide copolymers were well tolerated in acute toxicity studies in rats and therefore show promise as biomaterials.
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge 02139, USA.
J
J
Hanes
M
M
Chiba
R
R
Langer
D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000737:chemistry; D001672:Biocompatible Materials / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D002626:Chemistry, Pharmaceutical; D003652:Decanoic Acids / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D003692:Delayed-Action Preparations; D004655:Emulsions; D006863:Hydrogen-Ion Concentration; D046911:Macromolecular Substances; D008297:Male; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D011108:Polymers / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D011506:Proteins / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000737:chemistry; D012995:Solubility; D014867:Water / Q000737:chemistry
D000941:Antigens; D001672:Biocompatible Materials; D003652:Decanoic Acids; D003692:Delayed-Action Preparations; D004655:Emulsions; D046911:Macromolecular Substances; D011108:Polymers; D011506:Proteins; C114275:poly(trimellitylimido-tyrosine-co-sebacic acid-co-1,3-bis(carboxyphemoxy)propane) anhydride; D014867:Water; D012710:Serum Albumin, Bovine