Document Detail

Electrospray encapsulation of toll-like receptor agonist resiquimod in polymer microparticles for the treatment of visceral leishmaniasis.
MedLine Citation:
PMID:  23320733     Owner:  NLM     Status:  MEDLINE    
Leishmaniasis is a disease caused by the intracellular protozoan, Leishmania. 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 in vitro and in vivo. 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%. In vitro 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 Leishmania, 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.
Anthony D Duong; Sadhana Sharma; Kevin J Peine; Gaurav Gupta; Abhay R Satoskar; Eric M Bachelder; Barbra E Wyslouzil; Kristy M Ainslie
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2013-02-12
Journal Detail:
Title:  Molecular pharmaceutics     Volume:  10     ISSN:  1543-8392     ISO Abbreviation:  Mol. Pharm.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-03-04     Completed Date:  2013-09-04     Revised Date:  2014-03-06    
Medline Journal Info:
Nlm Unique ID:  101197791     Medline TA:  Mol Pharm     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1045-55     Citation Subset:  IM    
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MeSH Terms
Cell Line
Drug Carriers / administration & dosage,  chemistry
Imidazoles / administration & dosage*,  therapeutic use*
Leishmania donovani / pathogenicity
Leishmaniasis, Visceral / drug therapy*
Mice, Inbred BALB C
Microscopy, Electron, Scanning
Polymers / chemistry*
Toll-Like Receptors / agonists*
Grant Support
Reg. No./Substance:
0/Drug Carriers; 0/Imidazoles; 0/Polymers; 0/Toll-Like Receptors; V3DMU7PVXF/resiquimod

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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