Topical buparvaquone nano-enabled hydrogels for cutaneous leishmaniasis

Author(s)

Lalatsa, Aikaterini ^[1] ; Statts, Larry ^[1] ; de Jesus, Jessica Adriana ^[2] ; Adewusi, Olivia ^[1] ; Auxiliadora Dea-Ayuela, Maria ^[3] ; Bolas-Fernandez, Francisco ^[4] ; Laurenti, Marcia Dalastra ^[2] ; Domingues Passero, Luiz Felipe ^{[5, 2]} ; Serrano, Dolores R. ^{[6, 7, 8]}

Affiliation

^[1] Univ Portsmouth, Sch Pharm & Biomed Sci, Inst Biomed & Biomol Sci, Biomat Bioengn & Nanomed BioN Lab, White Swan Rd, Portsmouth PO1 2DT, Hants - England

^[2] Univ Sao Paulo, Med Sch, Lab Pathol Infect Dis LIM 50, Ave Dr Arnaldo 455, BR-01246903 Sao Paulo, SP - Brazil

^[3] Univ CEU Cardenal Herrera, Fac Ciencias Salud, Dept Farm, Edificio Seminario S-N, Valencia 46113 - Spain

^[4] Univ Complutense Madrid, Sch Pharm, Dept Microbiol & Parasitol, Plaza Ramon y Cajal S-N, Madrid 28040 - Spain

^[5] Sao Paulo State Univ UNESP, Inst Biosci, Praca Infante Dom Henrique S-N, BR-11330900 Sao Vicente, SP - Brazil

^[6] Sao Paulo State Univ UNESP, Inst Adv Studies Ocean Biosci, Av Joao Francisco Bensdorp 1178, BR-11350011 Sao Vicente, SP - Brazil

^[7] Univ Complutense Madrid, Dept Pharmaceut & Food Technol, Sch Pharm, Plaza Ramon y Cajal S-N, Madrid 28040 - Spain

^[8] Univ Complutense Madrid, Inst Univ Farm Ind IUFI, Sch Pharm, Plaza Ramon y Cajal S-N, Madrid 28040 - Spain

• Document type: Journal article
• Source: International Journal of Pharmaceutics; v. 588, OCT 15 2020.
• Web of Science Citations: 2

Abstract

Leishmaniasis is a neglected disease presenting cutaneous, mucosal and visceral forms and affecting an estimated 12 million mostly low-income people. Treatment of cutaneous leishmaniasis (CL) is recommended to expedite healing, reduce risk of scarring, prevent parasite dissemination to other mucocutaneous (common with New World species) or visceral forms and reduce the chance of relapse, but remains an unmet need. Available treatments are painful, prolonged (> 20 days) and require hospitalisation, which increases the cost of therapy. Here we present the development of optimised topical self-nanoemulsifying drug delivery systems (SNEDDS) loaded with buparvaquone (BPQ, a hydroxynapthoquinone from the open Malaria Box) for the treatment of CL from New World species. The administration of topical BPQ-SNEDDS gels for 7 days resulted in a reduction of parasite load of 99.989 +/- 0.019% similar to the decrease achieved with intralesionally administered Glucantime (R) (99.873 +/- 0.204%) in a L. amazonensis BALB/c model. In vivo efficacy was supported by ex vivo permeability and in vivo tape stripping studies. BPQ-SNEDDS and their hydrogels demonstrated linear flux across non-infected CD-1 mouse skin ex vivo of 182.4 +/- 63.0 mu g cm(-2) h(-1) and 57.6 +/- 10.8 mu g cm(-2 )h(-1) respectively localising BPQ within the skin in clinically effective concentrations (227.0 +/- 45.9 mu g and 103.8 +/- 33.8 mu g) respectively. These levels are therapeutic as BPQ-SNEDDS and their gels showed nanomolar in vitro efficacy against L. amazonensis and L. braziliensis amastigotes with excellent selectivity index toward parasites versus murine macrophages. In vivo tape stripping experiments indicated localisation of BPQ within the stratum corneum and dermis. Histology studies confirmed the reduction of parasitism and indicated healing in animals treated with BPQ-SNEDDS hydrogels. These results highlight the potential clinical capability of nano-enabled BPQ hydrogels towards a non-invasive treatment for CL. (AU)

• FAPESP's process: 16/00468-0 - Use of drug repurposing and natural product bioprospection to characterize compounds with in vitro and in vivo leishmanicidal action
• Grantee: Luiz Felipe Domingues Passero
• Support Opportunities: Regular Research Grants