Degradation of double-walled polymer microspheres of PLLA and P(CPP:SA)20:80. II. In vivo degradation.
Double-walled (DW) polymer microspheres with a core of poly(1,3-bis-(p-carboxyphenoxy propane)-co-(sebacic anhydride)20:80 (P(CPP:SA)20:80) and an external coat of poly(L-lactic acid) (PLLA) were implanted subcutaneously and intramuscularly and were allowed to degrade for up to 6 months. The tissue surrounding the implant was fixed and sectioned for histological evaluation by light and scanning electron microscopy. The remaining polymer was extracted with chloroform and analyzed by gel permeation chromatography (G PC), Fourier-transform infrared (FTIR) spectroscopy, and differential scanning calorimetry (DSC). The inner core of the more hydrolytically labile P(CPP:SA)20:80 degraded first, becoming more granular over time. The PLLA coating showed no changes morphologically. The DW microspheres induced a stronger inflammatory response during the first week than did the SW PLLA microspheres, but this resolved by the second week. The SW PLLA microspheres showed no changes by SEM or optical microscopy. No differences in degradation were seen between samples implanted subcutaneously and those implanted intramuscularly. In vivo degradation was correlated to the results of an in vitro degradation study published as the first paper in this two paper series.
Leach
K J
KJ
Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, Rhode Island 02912, USA.
Takahashi
S
S
Mathiowitz
E
E
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000493:pharmacokinetics*; D002152:Calorimetry, Differential Scanning; D003652:Decanoic Acids / Q000737:chemistry / Q000493:pharmacokinetics*; D004337:Drug Carriers; D005027:Ethylene Oxide; D020007:Implants, Experimental; D019344:Lactic Acid / Q000737:chemistry / Q000493:pharmacokinetics*; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D008970:Molecular Weight; D011091:Polyesters / Q000737:chemistry / Q000493:pharmacokinetics*; D011108:Polymers / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017550:Spectroscopy, Fourier Transform Infrared; D013242:Sterilization
D001672:Biocompatible Materials; D003652:Decanoic Acids; D004337:Drug Carriers; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide); C055401:decanedioic acid-4,4'-(1,3-propanediylbis(oxy))bis(benzoic acid) copolymer; D005027:Ethylene Oxide