Assessment of β-lapachone loaded in lecithin-chitosan nanoparticles for the topical treatment of cutaneous leishmaniasis in L. major infected BALB/c mice.
Patients affected by cutaneous leishmaniasis need a topical treatment which cures lesions without leaving scars. Lesions are produced not only by the parasite but also by an uncontrolled and persistent inflammatory immune response. In this study, we proposed the loading of β-lapachone (β-LP) in lecithin-chitosan nanoparticles (NP) for targeting the drug to the dermis, where infected macrophages reside, and promote wound healing. Although the loading of β-LP in NP did not influence the drug antileishmanial activity it was critical to achieve important drug accumulation in the dermis and permeation through the skin. When topically applied in Leishmania major infected BALB/c mice, β-LP NP achieved no parasite reduction but they stopped the lesion progression. Immuno-histopathological assays in CL lesions and quantitative mRNA studies in draining lymph nodes confirmed that β-LP exhibited anti-inflammatory activity leading to the down-regulation of IL-1β and COX-2 expression and a decrease of neutrophils infiltrate.


BACKGROUND
Cutaneous leishmaniasis often leaves patients with unsightly scars due to the body's inflammatory response to the infection. The authors in this paper described topical treatment using β-lapachone (β- LP) loaded in lecithin-chitosan nanoparticles (NP) in an animal model. Results confirmed the reduction of inflammatory response without affecting the parasite killing efficacy. These findings would pave way for further clinical testing in the near future.
Instituto de Salud Tropical, University of Navarra, Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IdISNA), Pamplona, Spain.
Esther
E
Moreno
Instituto de Salud Tropical, University of Navarra, Pamplona, Spain; Pharmacy and Pharmaceutical Technology Department, University of Navarra, Pamplona, Spain.
Juana
J
Schwartz
Instituto de Salud Tropical, University of Navarra, Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IdISNA), Pamplona, Spain.
Esther
E
Larrea
Pharmacy and Pharmaceutical Technology Department, University of Navarra, Pamplona, Spain.
Iosune
I
Conde
Instituto de Salud Tropical, University of Navarra, Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IdISNA), Pamplona, Spain; Organic and Pharmaceutical Chemistry Department, University of Navarra, Pamplona, Spain.
Maria
M
Font
Instituto de Salud Tropical, University of Navarra, Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IdISNA), Pamplona, Spain; Organic and Pharmaceutical Chemistry Department, University of Navarra, Pamplona, Spain.
Carmen
C
Sanmartín
Instituto de Investigación Sanitaria de Navarra (IdISNA), Pamplona, Spain; Pharmacy and Pharmaceutical Technology Department, University of Navarra, Pamplona, Spain.
Juan Manuel
JM
Irache
Instituto de Salud Tropical, University of Navarra, Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IdISNA), Pamplona, Spain; Pharmacy and Pharmaceutical Technology Department, University of Navarra, Pamplona, Spain. Electronic address: sespuelas@unav.es.
Socorro
S
Espuelas
D000287:Administration, Topical; D000818:Animals; D000977:Antiparasitic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D048271:Chitosan / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D054709:Lecithins / Q000737:chemistry*; D018320:Leishmania major / Q000187:drug effects*; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy* / Q000473:pathology; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D009285:Naphthoquinones / Q000008:administration & dosage / Q000627:therapeutic use*; D012867:Skin / Q000469:parasitology / Q000473:pathology
D000977:Antiparasitic Agents; D004337:Drug Carriers; D054709:Lecithins; D009285:Naphthoquinones; C014638:beta-lapachone; D048271:Chitosan
Cutaneous leishmaniasis; Cyclooxygenase-2; IL-1β; Lecithin-chitosan nanoparticles; Topical treatment; β-Lapachone