Curcumin-loaded self-emulsifying drug delivery system (cu-SEDDS): a promising approach for the control of primary pathogen and secondary bacterial infections in cutaneous leishmaniasis.

Cutaneous leishmaniasis being a neglected tropical disease (NTD) faces several challenges in chemotherapy. If infected with secondary bacterial infections, the treatment regime of cutaneous ulcers in cutaneous leishmaniasis is further complicated which usually require two or more than two chemotherapeutic agents for healing. In the current study, seven curcumin-loaded self-emulsifying drug delivery system (cu-SEDDS) formulations (namely F1-F7) were prepared by mixing different excipients (oils, surfactants, and co-solvents) through stirring (vortex) and sonication. The formulations were characterized regarding their droplet size, polydispersity index (PDI), and zeta potential by zeta sizer. The cu-SEDDS formulations displayed different sizes ranging from 32.4 up to 80.0 nm. The zeta potential of the formulations ranged from - 1.56 up to - 4.8. The antileishmanial activities of the cu-SEDDS formulations in terms of IC50 against Leishmania tropica ranged from 0.19 up to 0.37 µg/ml. The minimum inhibitory concentrations (MICs) of these formulations against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Klebsiella pneumoniae were in the range of 48-62 µg/ml. The hemolysis caused by formulations was 1-2%. The spreading potential of the formulations (F1 and F5) over damaged skin model was remarkable. These results suggest that cu-SEDDS further enhanced the broad spectrum antileishmanial and antibacterial profile of curcumin and could be used for the treatment of cutaneous leishmaniasis and its associated secondary infections.

Formulation and Characterization of a Self-Emulsifying Drug Delivery System (SEDDS) of Curcumin for the Topical Application in Cutaneous and Mucocutaneous Leishmaniasis.

BACKGROUND: Leishmaniasis, which is classified by the World Health Organization (WHO) as one of the Neglected Tropical Diseases (NTDs) faces several challenges in terms of successful chemotherapy and novel drug developments. OBJECTIVE: The aim of the present study was to develop a Self-Emulsifying Drug Delivery System (SEDDS) for the hydrophobic polyphenol pigment curcumin to enable it for its potential use in cutaneous and mucocutaneous leishmaniasis. METHODS: Two Curcumin-loaded formulations SNEDD-A and B, were developed. Both were characterized by the droplet size, PDI and zeta potential and evaluated for the cytotoxicity on Caco-2 cell lines and through hemolysis test on red blood cells. The spreading potential of the formulations was checked over buccal mucosa and damaged skin model. Antileishmanial activities were performed against promastigote, axenic amastigote and macrophage harbored amastigotes of Leishmania tropica parasite. RESULTS: SNEDDS-A and B had minor differences in physical characteristics. In the toxicological assay, the viability of the Caco-2 cells was 87.5 % for SNEDDS-A and 88.9% for SNEDDS-B while both caused 1-2% hemolysis. Both had remarkable spreading potential, covering 8cm2 of buccal mucosa and damaged the skin for less than 45 minutes. The Antileishmanial activities of the SNEDDS-A in terms of IC50 were 0.13 µg/ml and 0.25 µg/ml against promastigote and amastigote, respectively while IC50 values of SNEDDS-B were 0.18 µg/ml and 0.27 µg/ml against promastigote and amastigote, respectively. Both the formulations killed 100% of the macrophage harbored Leishmania tropica parasites at a concentration of 4.4 µg/ml. CONCLUSION: Our results demonstrate that both the SEDDS formulations of curcumin have the potential to provide a promising tool for curcumin for its use through topical routes in the treatment of cutaneous and mucocutaneous leishmaniasis.

Antimicrobial and antileishmanial studies of novel (2E)-3-(2-chloro-6-methyl/methoxyquinolin-3-yl)-1-(aryl)prop-2-en-1-ones.

Thirty eight heterocyclic chalcones were synthesized by condensing formylquinolines with diverse methyl arylketones. The target compounds were characterized by spectroscopic techniques (NMR, IR, MS) and elemental analysis. The X-ray crystallographic study of (2E)-3-(2-chloro-6-methylquinolin-3-yl)-1-(2,3-dihydro-1,4-benzodioxin-6-yl)prop-2-en-1-one (1p) was also performed for the structure confirmation. The title compounds were screened for anti-microbial and antileishmanial activities. The compounds 1c-e, 1g, 1j-m, 1p, 1r-s, 2g, 2j-p, and 2r-s were found potentially active antileishmanial agents, while 1f-i, 1l, 1o-p, 2f-i, 2l, and 2o-p showed remarkable antibacterial activity. Only compounds 1g and 2g-h exhibited significant antifungal activity.

Latent activity of curcumin against leishmaniasis in vitro.

In this study the anti-proliferative effect of curcumin (curcuma longa) that is the active ingredient of ground dried rhizome has been studied against three local and three reference leishmanial strains, Leishmania major, Leishmania tropica and Leishmania infantum (Pakistani isolate). Curcumin has shown an average IC50 of 5.3 microM against promastigotes of various leishmanial strains which is much lower as compared with pentamidine that is one of the basic treatments against leishmaniasis. The main draw back attributed to these assays performed on promastigotes is the heterogeneity of results compared with those obtained with intracellular amastigotes or with in vivo effect. We also tested activity of curcumin against axenic amastigote like cells (AALC) of L. major strain (MHOM/PK/88/DESTO). Curcumin proves to be far more potent then pentamidine against AALC which further strengthens the fact about its leishmaniacidal activity.