A biodegradable filament for controlled drug delivery.
Biodegradable filaments (diameters of 250-300 microm) for the controlled delivery of dexamethasone or levofloxacin are described. Filaments are prepared by wet-spinning solutions of poly(lactide-co-glycolide) (PLGA) and drug dissolved in dimethyl sulfoxide (DMSO) into a coagulation bath of water. Compositional analyses of the filaments by independent measurements of drug, DMSO, water, and polymer give drug loadings up to 40% of filament mass and drug retention (drug in filament per drug in solution) greater than 40%. Drug release kinetics, and thermal and mechanical properties, of the filaments are reported. Three filaments with levofloxacin contents of 46+/-2, 85+/-4, and 36+/-2 microg/cm (denoted 506-L1, 506-L2, and 506-L3, respectively) are implanted in the conjunctiva of New Zealand white rabbits. The time dependent, in-vivo tear concentrations of levofloxacin from filament implants in New Zealand white rabbit eyes are in general agreement with the results from the in-vitro release profiles, with one of the filaments (506-L1) showing effective levels of levofloxacin in the tears for 6 days. The filaments are generally well tolerated by the rabbits. Filament failure occurs at 6-8 days within the rabbit eyes, essentially the same time to failure observed from in-vitro mechanical properties testing results.
Mack
Brendan C
BC
Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, United States.
Wright
Kenneth W
KW
Davis
Mark E
ME
D020341:Absorbable Implants; D000287:Administration, Topical; D000818:Animals; D002626:Chemistry, Pharmaceutical; D003228:Conjunctiva / Q000378:metabolism*; D003692:Delayed-Action Preparations; D003907:Dexamethasone / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D004121:Dimethyl Sulfoxide / Q000737:chemistry; D004337:Drug Carriers; D004339:Drug Compounding; D019344:Lactic Acid / Q000737:chemistry*; D064704:Levofloxacin; D015242:Ofloxacin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011817:Rabbits; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013499:Surface Properties; D013666:Tears / Q000378:metabolism; D013718:Tensile Strength; D044366:Transition Temperature
D003692:Delayed-Action Preparations; D004337:Drug Carriers; D012997:Solvents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D064704:Levofloxacin; D003907:Dexamethasone; D015242:Ofloxacin; D004121:Dimethyl Sulfoxide