Controlled release of tetracycline from biodegradable beta-tricalcium phosphate composites.
For use in the prevention of bone infections, a novel controlled release system composed of beta-tricalcium phosphate (TCP) granules with biodegradable coatings incorporating the antibiotic drug tetracycline (TC) was developed. Six formulations using poly(D,L-lactide) and poly(D,L-lactide-co-glycolide) as coating materials to incorporate TC were prepared and tested in vitro and in vivo. Release of TC from TCP composites was dependent on the biodegradability of the used polymers and on physical-chemical interactions of TC with the polymer materials. Three characteristic release profiles were obtained: slow release lasting up to 67 days, intermediate release with 60% of the total dose released up to day 20, and fast release with a high initial burst and 90% of TC released within 4 days. Even though TC decomposition products had formed during in vitro release, no cytotoxic effects on osteoblast-like cells were observed. The biological activity of TC after incorporation into PL(G)A films was confirmed using a TC-repressible promoter system in genetically engineered Chinese Hamster Ovary (CHO) cells. TC-loaded TCP composites implanted in ovine cancellous bone defects showed good biocompatibility and new bone formation in the histological evaluation. No differences in the cellular reactions were seen between antibiotic-loaded composites and the control group. These experimental results indicate the potential of coated TCP composites to be used as local carrier system for controlled TC delivery with different release kinetics and good in vitro and in vivo biocompatibility.
Luginbuehl
Vera
V
Institute of Biotechnology, Zurich University of Applied Sciences, Grueental, Waedenswil CH-8820, Switzerland. vera.luginbuehl@zhaw.ch
Ruffieux
Kurt
K
Hess
Claudia
C
Reichardt
Dennis
D
von Rechenberg
Brigitte
B
Nuss
Katja
K
D020341:Absorbable Implants; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D001672:Biocompatible Materials; D016466:CHO Cells; D002130:Calcium Phosphates / Q000737:chemistry* / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D003412:Cricetulus; D016503:Drug Delivery Systems; D015745:Granuloma, Foreign-Body / Q000473:pathology; D019344:Lactic Acid; D008422:Materials Testing; D008855:Microscopy, Electron, Scanning; D010006:Osteoblasts / Q000187:drug effects; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012756:Sheep; D013752:Tetracycline / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity
D000900:Anti-Bacterial Agents; D001672:Biocompatible Materials; D002130:Calcium Phosphates; C485817:beta-tricalcium phosphate; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D013752:Tetracycline