Formulation and characterisation of a self-nanoemulsifying drug delivery system of amphotericin B for the treatment of leishmaniasis
- Author(s): Momin Khan 1, 2, 3 ; Akhtar Nadhman 4 ; Walayat Shah 3 ; Imran Khan 1, 5 ; Masoom Yasinzai 1, 6
-
-
View affiliations
-
Affiliations:
1:
Department of Biotechnology, Quaid-I-Azam University , Islamabad , Pakistan ;
2: Department of Pharmaceutical Technology, Institute of Pharmacy, Centre for Chemistry and Biomedicine (CCB) University of Innsbruck , Innsbruck , Austria ;
3: Institute of Basic Medical Sciences, Khyber Medical University , Peshawar , Pakistan ;
4: Institute of Integrative Biosciences, CECOS University of Science and Information Technology , Peshawar , Pakistan ;
5: Division of Cancer Epidemiology and Management, National Cancer Center-809 Madu-dong , Ilsan-gu, Goyang-si, Gyeonggi-do, 0-769 , Republic of Korea ;
6: Centre for Interdisciplinary Research in Basic Sciences, International Islamic University Islamabad , Islamabad , Pakistan
-
Affiliations:
1:
Department of Biotechnology, Quaid-I-Azam University , Islamabad , Pakistan ;
- Source:
Volume 13, Issue 5,
July
2019,
p.
477 – 483
DOI: 10.1049/iet-nbt.2018.5281 , Print ISSN 1751-8741, Online ISSN 1751-875X
This study was aimed to develop a self-nanoemulsifying drug delivery system (SNEDDS) for amphotericin B (AmB) potential use in leishmaniasis through topical and oral routes. Two formulations, formulation A and formulation B (FA and FB) of AmB loaded SNEDDS were developed by mixing their excipients through vortex and sonication. The SNEDDS formulation FA and FB displayed a mean droplet size of 27.70 ± 0.5 and 30.17 ± 0.7 nm and zeta potential −11.4 ± 3.25 and −13.6 ± 2.75 mV, respectively. The mucus permeation study showed that formulation FA and FB diffused 1.45 and 1.37%, respectively in up to 8 mm of mucus. The cell permeation across Caco-2 cells monolayer was 10 and 11%, respectively. Viability of Caco-2 cells was 89% for FA and 86.9% for FB. The anti-leishmanial activities of FA in terms of IC50 were 0.017 µg/ml against promastigotes and 0.025 µg/ml against amastigotes, while IC50 values of FB were 0.031 and 0.056 µg/ml, respectively. FA and FB killed macrophage harboured Leishmania parasites in a dose-dependent manner and a concentration of 0.1 µg/ml killed 100% of the parasites. These formulations have the potential to provide a promising tool for AmB use through oral and topical routes in leishmaniasis therapy.
Inspec keywords: drugs; nanomedicine; electrokinetic effects; diseases; drops; monolayers; microorganisms; cellular biophysics; drug delivery systems
Other keywords: topical routes; droplet size; Leishmania parasites; vortex; amastigotes; mucus permeation study; promastigotes; Caco-2 cell monolayer; Caco-2 cell viability; SNEDDS formulation; oral routes; zeta potential; leishmaniasis treatment; sonication; self-nanoemulsifying drug delivery system; amphotericin B; cell permeation; antileishmanial activity
Subjects: Nanotechnology applications in biomedicine; Patient care and treatment; Patient care and treatment; Cellular biophysics; Electrochemistry and electrophoresis
References
-
-
1)
-
24. O'Brien, J., Wilson, I., Orton, T., et al: ‘Investigation of the alamar blue (resazurin) fluorescent dye for the assessment of mammalian cell cytotoxicity’, Eur. J. Biochem., 2000, 267, (17), pp. 5421–5426.
-
-
2)
-
7. Sundar, S., More, D.K., Singh, M.K., et al: ‘Failure of pentavalent antimony in visceral leishmaniasis in India: report from the center of the Indian epidemic’, Clin. Infect. Dis., 2000, 31, (4), pp. 1104–1107.
-
-
3)
-
25. Bernkop-Schnurch, A., Jalil, A.: ‘Do drug release studies from SEDDS make any sense?’, J. Control Release, 2018, 271, pp. 55–59.
-
-
4)
-
18. Ahmad, J., Kohli, K., Mir, S.R., et al: ‘Self-emulsifying nano carriers for improved oral bioavailability of lipophilic drugs’, Rev. Adv. Sci. Eng., 2012, 1, (2), pp. 134–147.
-
-
5)
-
11. Ponte-Sucre, A., Gamarro, F., Dujardin, J.C., et al: ‘Drug resistance and treatment failure in leishmaniasis: a 21st century challenge’, PLoS Negl. Trop. Dis., 2017, 11, (12), p. e0006052.
-
-
6)
-
8. Sundar, S., Mehta, H., Suresh, A.V., et al: ‘Amphotericin B treatment for Indian visceral leishmaniasis: conventional versus lipid formulations’, Clin. Infect. Dis., 2004, 38, (3), pp. 377–383.
-
-
7)
-
28. Nadhman, A., Nazir, S., Khan, M.I., et al: ‘PEGylated silver doped zinc oxide nanoparticles as novel photosensitizers for photodynamic therapy against leishmania’, Free Radical Biol. Med., 2014, 77, pp. 230–238.
-
-
8)
-
27. Dutta, A., Bandyopadhyay, S., Mandal, C., et al: ‘Development of a modified MTT assay for screening antimonial resistant field isolates of Indian visceral leishmaniasis’, Parasitol. Int., 2005, 54, (2), pp. 119–122.
-
-
9)
-
4. Santos, D.O., Coutinho, C.E., Madeira, M.F., et al: ‘Leishmaniasis treatment—a challenge that remains: a review’, Parasitol. Res., 2008, 103, (1), pp. 1–10.
-
-
10)
-
12. https://www.dndi.org/diseases-projects/leishmaniasis/, accessed May 31 2018 2018.
-
-
11)
-
20. Jennings, P., Koppelstaetter, C., Aydin, S., et al: ‘Cyclosporine A induces senescence in renal tubular epithelial cells’, Am. J. Physiol. Renal. Physiol., 2007, 293, (3), pp. F831–F838.
-
-
12)
-
32. Zhang, H., Yao, M., Morrison, R.A., et al: ‘Commonly used surfactant, tween 80, improves absorption of P-glycoprotein substrate, digoxin, in rats’, Arch. Pharmacal Res., 2003, 26, (9), pp. 768–772.
-
-
13)
-
36. Efiana, N.A., Phan, T.N.Q., Wicaksono, A.J., et al: ‘Mucus permeating self-emulsifying drug delivery systems (SEDDS): about the impact of mucolytic enzymes’, Colloids Surf. B, Biointerfaces, 2018, 1, (161), pp. 228–235.
-
-
14)
-
30. Kauffman, A.L., Gyurdieva, A.V., Mabus, J.R., et al: ‘Alternative functional in vitro models of human intestinal epithelia’, Front. Pharmacol., 2013, 4, p. 79.
-
-
15)
-
33. van Zuylen, L., Karlsson, M.O., Verweij, J., et al: ‘Pharmacokinetic modeling of paclitaxel encapsulation in cremophor EL micelles’, Cancer Chemother. Pharmacol., 2001, 47, (4), pp. 309–318.
-
-
16)
-
22. Dunnhaupt, S., Barthelmes, J., Hombach, J., et al: ‘Distribution of thiolated mucoadhesive nanoparticles on intestinal mucosa’, Int. J. Pharm., 2011, 408, (1–2), pp. 191–199.
-
-
17)
-
15. Wasan, E.K., Bartlett, K., Gershkovich, P., et al: ‘Development and characterization of oral lipid-based amphotericin B formulations with enhanced drug solubility, stability and antifungal activity in rats infected with Aspergillus fumigatus or Candida albicans’, Int. J. Pharm., 2009, 372, (1–2), pp. 76–84.
-
-
18)
-
31. Elbahwy, I.A., Lupo, N., Ibrahim, H.M., et al: ‘Mucoadhesive self-emulsifying delivery systems for ocular administration of econazole’, Int. J. Pharm., 2018, 25, pp. 72–80.
-
-
19)
-
3. Chakravarty, J., Sundar, S.: ‘Drug resistance in leishmaniasis’, J. Glob. Infect. Dis., 2010, 2, (2), pp. 167–176.
-
-
20)
-
9. Thakur, C.P., Pandey, A.K., Sinha, G.P., et al: ‘Comparison of three treatment regimens with liposomal amphotericin B (AmBisome) for visceral leishmaniasis in India: a randomized dose-finding study’, Trans. R. Soc. Trop. Med. Hyg., 1996, 90, (3), pp. 319–322.
-
-
21)
-
16. Zupancic, O., Partenhauser, A., Lam, H.T., et al: ‘Development and in vitro characterisation of an oral self-emulsifying delivery system for daptomycin’, Eur. J. Pharm. Sci., 2016, 81, pp. 129–136.
-
-
22)
-
2. Yasinzai, M., Khan, M., Nadhman, A., et al: ‘Drug resistance in leishmaniasis: current drug-delivery systems and future perspectives’, Future Med. Chem., 2013, 5, (15), pp. 1877–1888.
-
-
23)
-
34. Saha, P., Kou, J.H.: ‘Effect of solubilizing excipients on permeation of poorly water-soluble compounds across Caco-2 cell monolayers’, Eur. J. Pharm. Biopharm., 2000, 50, (3), pp. 403–411.
-
-
24)
-
14. Javed, I., Hussain, S.Z., Ullah, I., et al: ‘Synthesis, characterization and evaluation of lecithin-based nanocarriers for the enhanced pharmacological and oral pharmacokinetic profile of amphotericin B’, J. Mater. Chem. B, 2015, 3, (42), pp. 8359–8365.
-
-
25)
-
17. Fricker, G., Kromp, T., Wendel, A., et al: ‘Phospholipids and lipid-based formulations in oral drug delivery’, Pharm. Res., 2010, 27, (8), pp. 1469–1486.
-
-
26)
-
29. Nadhman, A., Nazir, S., Khan, M.I., et al: ‘Visible-light-responsive ZnCuO nanoparticles: benign photodynamic killers of infectious protozoans’, Int. J. Nanomed., 2015, 10, pp. 6891–6903.
-
-
27)
-
10. Wortmann, G., Zapor, M., Ressner, R., et al: ‘Lipsosomal amphotericin B for treatment of cutaneous leishmaniasis’, Am. J. Trop. Med. Hyg., 2010, 83, (5), pp. 1028–1033.
-
-
28)
-
35. Griesser, J., Hetényi, G., Kadas, H., et al: ‘Self-emulsifying peptide drug delivery systems: How to make them highly mucus permeating’, Int. J. Pharm., 2018, 1, pp. 159–166.
-
-
29)
-
6. Goyeneche-Patino, D.A., Valderrama, L., Walker, J., et al: ‘Antimony resistance and trypanothione in experimentally selected and clinical strains of leishmania panamensis’, Antimicrob. Agents Chemother., 2008, 52, (12), pp. 4503–4506.
-
-
30)
-
26. Walker, M., Hulme, T.A., Rippon, M.G., et al: ‘In vitro model(s) for the percutaneous delivery of active tissue repair agents’, J. Pharm. Sci., 1997, 86, (12), pp. 1379–1384.
-
-
31)
-
23. Pereira de Sousa, I., Cattoz, B., Wilcox, M.D., et al: ‘Nanoparticles decorated with proteolytic enzymes, a promising strategy to overcome the mucus barrier’, Eur. J. Pharm. Biopharm., 2015, 97, (Pt A), pp. 257–264.
-
-
32)
-
19. Nigade, P.M., Patil, S.L., Tiwari, S.S.: ‘Self emulsifying drug delivery system (SEDDS): a review’, Int. J. Pharm. Biol. Sci., 2012, 2, (2), pp. 42–52.
-
-
33)
-
13. Pouton, C.W.: ‘Formulation of poorly water-soluble drugs for oral administration: physicochemical and physiological issues and the lipid formulation classification system’, Eur. J. Pharm. Sci., 2006, 29, (3), pp. 278–287.
-
-
34)
-
5. van Griensven, J., Balasegaram, M., Meheus, F., et al: ‘Combination therapy for visceral leishmaniasis’, Lancet Infect. Dis., 2010, 10, (3), pp. 184–194.
-
-
35)
-
1. http://www.who.int/leishmaniasis/en/, accessed May 31 2018.
-
-
36)
-
21. Kollner, S., Nardin, I., Markt, R., et al: ‘Self-emulsifying drug delivery systems: design of a novel vaginal delivery system for curcumin’, Eur. J. Pharm. Biopharm., 2017, 115, pp. 268–275.
-
-
1)