title: Long-term delivery of ivermectin by use of poly(D,L-lactic-co-glycolic)acid microparticles in dogs.
abstract: OBJECTIVE
  To evaluate the potential utility of poly(D,L-lactic-co-glycolic)acid (PLGA) as a long-acting biodegradable drug delivery matrix for ivermectin used in the prevention of heartworm disease in dogs.
  
  
  METHODS
  30 adult female dogs.
  
  
  METHODS
  Microparticle formulations containing 25 weight percent (wt%), 35 wt%, and 50 wt% ivermectin were prepared by an oil-in-water emulsion technique with solvent extraction into excess water. A fourth formulation, consisting of a mixture of 15 wt% and 50 wt% ivermectin microparticles, was blended in a 1:1 ratio to result in a 32.5 wt% ivermectin formulation. Formulations were administered once on Day 0 to groups of 6 dogs at a dose of 0.5 mg of ivermectin/kg, s.c. Half of the dogs in each treatment group and 3 untreated control dogs were infected with Dirofilaria immitis larvae 121 and 170 days after treatment. Six months after infection, dogs were euthanatized and necropsies were performed. Pharmacokinetics and efficacy were investigated.
  
  
  RESULTS
  Analysis of pharmacokinetic data revealed sustained release of ivermectin during at least 287 days in 3 distinct phases: a small initial peak, followed by release of drug through diffusion, and polymer degradation. Untreated control dogs were all infected with heartworms. Heartworms were not found in any of the dogs in the ivermectin-PLGA treated groups. Adverse clinical signs were not observed.
  
  
  CONCLUSIONS
  All formulations were 100% effective in preventing development of adult heartworms. Results indicate that PLGA microparticles are a promising drug delivery matrix for use with ivermectin for the prevention of heartworm disease for at least 6 months after treatment.
authors.affiliation: PR Pharmaceuticals Inc, 1716 Heath Pkwy, Fort Collins, CO 80525, USA.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Clark
authors.forename: Angela J
authors.initials: AJ
authors.lastname: Crowley
authors.forename: Paul G
authors.initials: PG
authors.lastname: Schmidt
authors.forename: Ann R
authors.initials: AR
authors.lastname: Donoghue
authors.forename: Claude A
authors.initials: CA
authors.lastname: Piché
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004182:Dirofilaria; D004184:Dirofilariasis / Q000188:drug therapy* / Q000517:prevention & control; D004283:Dog Diseases / Q000469:parasitology / Q000517:prevention & control*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000627:therapeutic use; D004341:Drug Evaluation; D005369:Filaricides / Q000627:therapeutic use*; D007559:Ivermectin / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019344:Lactic Acid / Q000627:therapeutic use*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000627:therapeutic use*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D004337:Drug Carriers; D005369:Filaricides; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D007559:Ivermectin