In vitro study of drug-eluting stent coatings based on poly(L-lactide) incorporating cyclosporine A - drug release, polymer degradation and mechanical integrity.
In this study, absorbable polymer stent coatings for localized drug delivery based on poly(L-lactide) (PLLA) and cyclosporine A (CsA) were developed and tested in vitro. Metallic stents were coated with different compositions of PLLA/CsA (70/30, 60/40, 50/50% w/w) and beta-sterilized. The specimens were used to assess the drug release kinetics with HPLC. Sterilization influenced polymer degradation was measured with GPC. Mechanical integrity of the stent coatings was studied with SEM. The interconnection of the coated stents with a balloon-catheter was characterized by the measurement of stent dislodgment force. A migration assay was used to determine the inhibitory effect of the model drug CsA on smooth muscle cell (SMC) migration. The release of CsA was established over time periods up to 24 days in sodium chloride solution and in porcine blood plasma. An inhibition of SMC migration (max. 26-33%) was found for CsA concentrations of 4 x 10(-5) to 4 x 10(-7) mol/l. Marked molecular weight reduction (70-80%) of the PLLA matrix occurred after beta-sterilization. We also observed a substantial decrease of in vitro degradation time. The maintenance of the mechanical integrity of the polymer coating during crimping and dilation of the specimens could be verified, and a sufficient stent dislodgment force of 0.8-0.9 N was measured.
Sternberg
Katrin
K
Institute for Biomedical Engineering, University of Rostock, Ernst-Heydemann-Str. 6, 18057 Rostock, Germany. katrin.sternberg@uni-rostock.de
Kramer
Sven
S
Nischan
Claudia
C
Grabow
Niels
N
Langer
Thomas
T
Hennighausen
Gerhard
G
Schmitz
Klaus-Peter
KP
D020341:Absorbable Implants; D000818:Animals; D001807:Blood Vessel Prosthesis; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible / Q000008:administration & dosage / Q000737:chemistry; D016572:Cyclosporine / Q000008:administration & dosage*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry*; D004058:Diffusion; D004337:Drug Carriers / Q000737:chemistry; D019544:Equipment Failure Analysis; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000737:chemistry; D008422:Materials Testing; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology*; D011091:Polyesters / Q000737:chemistry*; D051381:Rats; D015607:Stents; D013718:Tensile Strength
D020099:Coated Materials, Biocompatible; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D007166:Immunosuppressive Agents; D011091:Polyesters; C033616:poly(lactide); D016572:Cyclosporine