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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

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Abstract

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.

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References

  • Ahmad J, Kohli K, Mir SR, Amin S (2012) Self-emulsifying nano carriers for improved oral bioavailability of lipophilic drugs. Rev Adv Sci Eng 1(2):134–147

    Article  Google Scholar 

  • CLSI (2013) Clinical and Laboratory Standards Institute Standards Development Policies and Processes. CLSI S-001/3.0

  • Debata PR, Castellanos MR, Fata JE, Baggett S, Rajupet S, Szerszen A, Begum S, Mata A, Murty VV, Opitz LM, Banerjee P (2013) A novel curcumin-based vaginal cream Vacurin selectively eliminates apposed human cervical cancer cells. Gynecol Oncol 129(1):145–153

    Article  CAS  PubMed  Google Scholar 

  • Dutta A, Bandyopadhyay S, Mandal C, Chatterjee M (2005) Development of a modified MTT assay for screening antimonial resistant field isolates of Indian visceral leishmaniasis. Parasitol Int 54(2):119–122

    Article  CAS  PubMed  Google Scholar 

  • Ekrami A, Kalantar E (2007) Bacterial infections in burn patients at a burn hospital in Iran. Indian J Med Res 126(6):541

    PubMed  Google Scholar 

  • Fontes CO, Carvalho MAR, Nicoli JR, Hamdan JS, Mayrink W, Genaro O, Carmo LS, Farias LM (2005) Identification and antimicrobial susceptibility of micro-organisms recovered from cutaneous lesions of human American Tegumentary leishmaniasis in Minas Gerais, Brazil. J Med Microbiol 54(11):1071–1076

    Article  CAS  PubMed  Google Scholar 

  • Fouladvand M, Barazesh A, Tahmasebi R (2013) Evaluation of in vitro antileishmanial activity of curcumin and its derivatives “Gallium curcumin, Indium curcumin and Diacethyle curcumin”. Eur Rev Med Pharmacol Sci 17(24):3306–3308

    CAS  PubMed  Google Scholar 

  • Fricker G, Kromp T, Wendel A, Blume A, Zirkel J, Rebmann H, Setzer C, Quinkert RO, Martin F, Muller-Goymann C (2010) Phospholipids and lipid-based formulations in oral drug delivery. Pharm Res 27(8):1469–1486

    Article  CAS  PubMed  Google Scholar 

  • Georgiadou SP, Makaritsis KP, Dalekos GN (2015) Leishmaniasis revisited: current aspects on epidemiology, diagnosis and treatment. J Transl Int Med 3(2):43–50

    Article  PubMed  PubMed Central  Google Scholar 

  • Gunes H, Gulen D, Mutlu R, Gumus A, Tas T, Topkaya AE (2016) Antibacterial effects of curcumin: an in vitro minimum inhibitory concentration study. Toxicol Ind Health 32(2):246–250

    Article  CAS  PubMed  Google Scholar 

  • Gupta SC, Prasad S, Kim JH, Patchva S, Webb LJ, Priyadarsini IK, Aggarwal BB (2011) Multitargeting by curcumin as revealed by molecular interaction studies. Nat Prod Rep 28(12):1937–1955

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Khan M, Nadhman A, Sehgal SA, Siraj S, Yasinzai MM (2018) Formulation and characterization of a self-emulsifying drug delivery system (SEDDS) of curcumin for the topical application in cutaneous and mucocutaneous leishmaniasis. Curr Top Med Chem 18(18):1603–1609

    Article  CAS  PubMed  Google Scholar 

  • Khan M, Khan I, Nadhman A, Yasinzai M, Shah W (2019) Formulation and characterization of a self-nanoemulsifying drug delivery system of amphotericin B for the treatment of leishmaniasis. IET Nanobiotechnol. https://doi.org/10.1049/iet-nbt.2018.5281

  • Kollner S, Nardin I, Markt R, Griesser J, Prufert F, Bernkop-Schnurch A (2017) Self-emulsifying drug delivery systems: design of a novel vaginal delivery system for curcumin. Eur J Pharm Biopharm 115:268–275

    Article  CAS  PubMed  Google Scholar 

  • Maheshwari RK, Singh AK, Gaddipati J, Srimal RC (2006) Multiple biological activities of curcumin: a short review. Life Sci 78(18):2081–2087

    Article  CAS  PubMed  Google Scholar 

  • Moghadamtousi SZ, Kadir HA, Hassandarvish P, Tajik H, Abubakar S, Zandi K (2014) A review on antibacterial, antiviral, and antifungal activity of curcumin. Biomed Res Int 2014:186864

    PubMed  Google Scholar 

  • Moghaddam K, Iranshahi M, Yazdi M, Shahverdi A (2009) The combination effect of curcumin with different antibiotics against Staphylococcus aureus. Int J Green Pharm 3(2):141–3. https://doi.org/10.4103/0973-8258.54906

  • Nederberg F, Zhang Y, Tan JP, Xu K, Wang H, Yang C, Gao S, Guo XD, Fukushima K, Li L, Hedrick JL, Yang YY (2011) Biodegradable nanostructures with selective lysis of microbial membranes. Nat Chem 3(5):409–414

    Article  CAS  PubMed  Google Scholar 

  • Nigade PM, Patil SL, Tiwari SS (2012) Self emulsifying drug delivery system (SEDDS): a review. Int J Pharm Bio Sci 2(2):42–52

    CAS  Google Scholar 

  • Pandey A, Gupta RK, Bhargava A, Agrawal B (2011) Antibacterial activities of curcumin bioconjugates. Int J Pharmacol 7:874–879

    Article  CAS  Google Scholar 

  • Parasad EHB, Bhaskar Rao A, Reddy G (2014) Biotransformation of curcumin for improved biological activity and antiproliferative activity on acute HT-29 human cell lines. Indian J Biotechnol 13:324–329

    Google Scholar 

  • Saleheen D, Ali SA, Ashfaq K, Siddiqui AA, Agha A, Yasinzai MM (2002) Latent activity of curcumin against leishmaniasis in vitro. Biol Pharm Bull 25(3):386–389

    Article  CAS  PubMed  Google Scholar 

  • Sivasothy Y, Sulaiman SF, Ooi KL, Ibrahim H, Awang K (2013) Antioxidant and antibacterial activities of flavonoids and curcuminoids from Zingiber spectabile Griff. Environ Microbiol 30(2):714–720

    CAS  Google Scholar 

  • Struve C, Krogfelt KA (2004) Pathogenic potential of environmental Klebsiella pneumoniae isolates. Environ Microbiol 6(6):584–590

    Article  PubMed  Google Scholar 

  • Tajbakhsh S, Mohammadi K, Deilami I, Zandi K, Fouladvand M, Ramedani E, Asayesh G (2008) Antibacterial activity of Indium curcumin and Indium diacetylcurcumin. Afr J Biotechnol 7(21):3832–3835

    CAS  Google Scholar 

  • van Zuylen L, Karlsson MO, Verweij J, Brouwer E, de Bruijn P, Nooter K, Stoter G, Sparreboom A (2001) Pharmacokinetic modeling of paclitaxel encapsulation in Cremophor EL micelles. Cancer Chemother Pharmacol 47(4):309–318

    Article  CAS  PubMed  Google Scholar 

  • Walker M, Hulme TA, Rippon MG, Walmsley RS, Gunnigle S, Lewin M, Winsey S (1997) In vitro model(s) for the percutaneous delivery of active tissue repair agents. J Pharm Sci 86(12):1379–1384

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Lu Z, Wu H, Lv F (2009) Study on the antibiotic activity of microcapsule curcumin against foodborne pathogens. Int J Food Microbiol 136(1):71–74

    Article  CAS  PubMed  Google Scholar 

  • Yasinzai M, Khan M, Nadhman A, Shahnaz G (2013) Drug resistance in leishmaniasis: current drug-delivery systems and future perspectives. Future Med Chem 5(15):1877–1888

    Article  CAS  PubMed  Google Scholar 

  • Zhang H, Yao M, Morrison RA, Chong S (2003) Commonly used surfactant, Tween 80, improves absorption of P-glycoprotein substrate, digoxin, in rats. Arch Pharm Res 26(9):768–772

    Article  CAS  PubMed  Google Scholar 

  • Ziaei H, Sadeghian G, Hejazi S (2008) Distribution frequency of pathogenic bacteria isolated from cutaneus leishmaniasis lesions. Kor J Parasitol 46(3):191

    Article  Google Scholar 

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Acknowledgments

We are thankful to Prof. Andreas Bernkop-Schnürch (Department of Pharmaceutical Technology, Centre for Chemistry and Biomedicine (CCB) Innsbruck Austria) for the reagents, support, and encouragement. In addition we are thankful to Dr. Nazma Habib Khan for providing Leishmania tropica strain KWH23.

Funding

This work was financially supported by the Higher Education Commission of Pakistan.

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Correspondence to Muhammad Ali or Muhammad Masoom Yasinzai.

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This article contains some studies with human participants for which ethical approval was obtained from the Institutional Ethical Committee. For isolation of secondary bacterial infections, written and informed consent was obtained from the patients or their guardians (for children).

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Khan, M., Ali, M., Shah, W. et al. 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. Appl Microbiol Biotechnol 103, 7481–7490 (2019). https://doi.org/10.1007/s00253-019-09990-x

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