Biodegradable controlled antibiotic release devices for osteomyelitis: optimization of release properties.
Controlled antibiotic release films, melt-extruded cylinders, and suspension-extruded/coated cylinders were manufactured from biodegradable poly(D,L-lactide) (PDLLA) and poly(D,L-lactide-co-epsilon-caprolactone). These devices have potential application in the treatment of osteomyelitis. The in-vitro release properties of the devices were examined with drug loadings varying from 16 to 50%. Gentamicin sulphate films and melt-extruded gentamicin/PDLLA cylinders demonstrated a large initial burst and incomplete release. The films and melt-extruded cylinders made from poly(D,L-lactide-co-epsilon-caprolactone), low mol. wt poly(D,L-lactide), and a mixture of D,L-lactic acid oligomer and high mol. wt poly(D,L-lactide), did not remain intact during the entire release period. While this is undesirable, these materials do have the advantage of not requiring a processing temperature of greater than 110 degrees C. Antibiotic release from high mol. wt PDLLA-coated gentamicin/PDLLA cylinders, with 40 and 50% loading, was very rapid. The antibiotic could only diffuse out through the open ends of the cylinder. Coated gentamicin sulphate cylinders with 20 and 30% drug loading gave the most promising properties in terms of a small initial burst, and a gradual and sustained release. The release rate and duration from the coated cylinders could be adjusted by cutting the cylinder into different lengths; the time required for 90% of the entrapped gentamicin to be released into water from 30% loaded PDLLA-coated cylinders 0.2, 0.4, 0.7 and 1 cm in length was 1000, 1700, 2300, and 2800 h, respectively. This offers a convenient method to adjust the release to meet the specific antibiotic requirement of different patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Chemical Engineering, Queen's University, Kingston, Ontario, Canada.
X
X
Zhang
U P
UP
Wyss
D
D
Pichora
M F
MF
Goosen
D001672:Biocompatible Materials / Q000737:chemistry; D001673:Biodegradation, Environmental; D002437:Cefazolin / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D005839:Gentamicins / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D007773:Lactates / Q000737:chemistry; D019344:Lactic Acid; D010019:Osteomyelitis / Q000188:drug therapy* / Q000378:metabolism; D010400:Penicillin G / Q000493:pharmacokinetics; D011091:Polyesters / Q000737:chemistry; D011108:Polymers / Q000737:chemistry
D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D005839:Gentamicins; D007773:Lactates; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide); C062968:lactide-caprolactone copolymer; D002437:Cefazolin; D010400:Penicillin G