Electrospray Encapsulation
of Toll-Like Receptor Agonist
Resiquimod in Polymer Microparticles for the Treatment of Visceral
Leishmaniasis
- Publication date
- Publisher
Abstract
Leishmaniasis is a disease caused by the intracellular
protozoan, <i>Leishmania</i>. A current treatment for cutaneous
leishmaniasis
involves the delivery of imidazoquinolines via a topical cream. However,
there are no parenteral formulations of imidazoquinolines for the
most deadly version of the disease, visceral leishmaniasis. This work
investigates the use of electrospray to encapsulate the imidazoquinoline
adjuvant resiquimod in acid sensitive microparticles composed of acetalated
dextran (Ac-DEX) or Ac-DEX/Tween blends. The particles were characterized
and tested both <i>in vitro</i> and <i>in vivo</i>. Solutions of Ac-DEX and resiquimod in ethanol were electrosprayed
to generate approximately 2 μm Ac-DEX particles containing resiquimod
with an encapsulation efficiency of 85%. To prevent particle aggregation,
blends of Ac-DEX with Tween 20 and Tween 80 were investigated. Tween
80 was then blended with the Ac-DEX at ∼10% (w/w) of total
polymer and particles containing resiquimod were formed via electrospray
with encapsulation efficiencies between 40% and 60%. <i>In vitro</i> release profiles of resiquimod from Ac-DEX/Tween 80 particles exhibited
the acid-sensitive nature of Ac-DEX, with 100% drug release after
8 h at pH 5 (phagosomal pH) and after 48 h at pH 7.4 (physiological
pH). Treatment with Ac-DEX/Tween 80 particles elicited significantly
greater immune response in RAW macrophages over free drug. When injected
intravenously into mice inoculated with <i>Leishmania</i>, parasite load reduced significantly in the bone marrow compared
to blank particles and phosphate-buffered saline controls. Overall,
electrospray appears to offer an elegant, scalable way to encapsulate
adjuvant into an acid sensitive delivery vehicle for use in treating
visceral leishmaniasis