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.
Animals—30 adult female dogs.
Procedure—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, SC. 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 and Clinical Relevance—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. (Am J
Vet Res 2004;65:752–757)