Assessment of β-lapachone loaded in lecithin-chitosan nanoparticles for the topical treatment of cutaneous leishmaniasis in L-major infected BALB/c mice

被引:48
作者
Moreno, Esther [1 ,2 ]
Schwartz, Juana [1 ,3 ]
Larrea, Esther [1 ,2 ]
Conde, Iosune [3 ]
Font, Maria [1 ,2 ,4 ]
Sanmartin, Carmen [1 ,2 ,4 ]
Manuel Irache, Juan [2 ,3 ]
Espuelas, Socorro [1 ,2 ,3 ]
机构
[1] Univ Navarra, Inst Salud Trop, Pamplona 31008, Spain
[2] Inst Invest Sanitaria Navarra IdISNA, Pamplona, Spain
[3] Univ Navarra, Pharm & Pharmaceut Technol Dept, Pamplona 31008, Spain
[4] Univ Navarra, Organ & Pharmaceut Chem Dept, Pamplona 31008, Spain
关键词
beta-Lapachone; Lecithin-chitosan nanoparticles; Cutaneous leishmaniasis; Topical treatment; IL-1; beta; Cyclooxygenase-2; IN-VITRO; LECITHIN/CHITOSAN NANOPARTICLES; VISCERAL LEISHMANIASIS; AMPHOTERICIN-B; PAROMOMYCIN; IMMUNITY; GENTAMICIN; ACTIVATION; DELIVERY;
D O I
10.1016/j.nano.2015.07.011
中图分类号
TB3 [工程材料学];
学科分类号
0805 ; 080502 ;
摘要
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 beta-lapachone (beta-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 beta-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, beta-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 beta-LP exhibited anti-inflammatory activity leading to the down-regulation of IL-1 beta and COX-2 expression and a decrease of neutrophils infiltrate. From the Clinical Editor: 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 beta-lapachone (beta-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. (C) 2015 Elsevier Inc. All rights reserved.
引用
收藏
页码:2003 / 2012
页数:10
相关论文
共 52 条
[1]  
[Anonymous], 2009, OPEN NAT PROD J, DOI DOI 10.2174/1874848100902010042
[2]  
Araujo AP, 2015, ARCH DERMATOL RES
[3]   Immunoadjuvant Chemotherapy of Visceral Leishmaniasis in Hamsters Using Amphotericin B-Encapsulated Nanoemulsion Template-Based Chitosan Nanocapsules [J].
Asthana, Shalini ;
Jaiswal, Anil K. ;
Gupta, Pramod K. ;
Pawar, Vivek K. ;
Dube, Anuradha ;
Chourasia, Manish K. .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2013, 57 (04) :1714-1722
[4]   Topical Paromomycin with or without Gentamicin for Cutaneous Leishmaniasis [J].
Ben Salah, Afif ;
Ben Messaoud, Nathalie ;
Guedri, Evelyn ;
Zaatour, Amor ;
Ben Alaya, Nissaf ;
Bettaieb, Jihene ;
Gharbi, Adel ;
Hamida, Nabil Belhadj ;
Boukthir, Aicha ;
Chlif, Sadok ;
Abdelhamid, Kidar ;
El Ahmadi, Zaher ;
Louzir, Hechmi ;
Mokni, Mourad ;
Morizot, Gloria ;
Buffet, Pierre ;
Smith, Philip L. ;
Kopydlowski, Karen M. ;
Kreishman-Deitrick, Mara ;
Smith, Kirsten S. ;
Nielsen, Carl J. ;
Ullman, Diane R. ;
Norwood, Jeanne A. ;
Thorne, George D. ;
McCarthy, William F. ;
Adams, Ryan C. ;
Rice, Robert M. ;
Tang, Douglas ;
Berman, Jonathan ;
Ransom, Janet ;
Magill, Alan J. ;
Grogl, Max .
NEW ENGLAND JOURNAL OF MEDICINE, 2013, 368 (06) :524-532
[5]   Glycyrrhizic acid suppresses Cox-2-mediated anti-inflammatory responses during Leishmania donovani infection [J].
Bhattacharjee, Surajit ;
Bhattacharjee, Amrita ;
Majumder, Saikat ;
Majumdar, Suchandra Bhattacharya ;
Majumdar, Subrata .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2012, 67 (08) :1905-1914
[6]   Treatment of experimental leishmaniasis with the immunomodulators imiquimod and S-28463: Efficacy and mode of action [J].
Buates, S ;
Matlashewski, G .
JOURNAL OF INFECTIOUS DISEASES, 1999, 179 (06) :1485-1494
[7]   A Targeted and Adjuvanted Nanocarrier Lowers the Effective Dose of Liposomal Amphotericin B and Enhances Adaptive Immunity in Murine Cutaneous Leishmaniasis [J].
Daftarian, Pirouz M. ;
Stone, Geoffrey W. ;
Kovalski, Leticia ;
Kumar, Manoj ;
Vosoughi, Aram ;
Urbieta, Maitee ;
Blackwelder, Pat ;
Dikici, Emre ;
Serafini, Paolo ;
Duffort, Stephanie ;
Boodoo, Richard ;
Rodriguez-Cortes, Alheli ;
Lemmon, Vance ;
Deo, Sapna ;
Alberola, Jordi ;
Perez, Victor L. ;
Daunert, Sylvia ;
Ager, Arba L. .
JOURNAL OF INFECTIOUS DISEASES, 2013, 208 (11) :1914-1922
[8]  
Dai TH, 2011, EXPERT REV ANTI-INFE, V9, P857, DOI [10.1586/eri.11.59, 10.1586/ERI.11.59]
[9]   Cutaneous and mucocutaneous leishmaniasis [J].
David, Consuelo V. ;
Craft, Noah .
DERMATOLOGIC THERAPY, 2009, 22 (06) :491-502
[10]   Vesicles as tools for the modulation of skin permeability [J].
Dubey, Vaibhav ;
Mishra, Dinesh ;
Nahar, Manoj ;
Jain, Narendra K. .
EXPERT OPINION ON DRUG DELIVERY, 2007, 4 (06) :579-593