Skip to main content

Advertisement

SpringerLink
Log in

Nanoformulation of Leonotis leonurus to improve its bioavailability as a potential antidiabetic drug

  • Original Article
  • Published:
3 Biotech Aims and scope Submit manuscript

Abstract

Nanostructured lipid carriers (NLCs) of Leonotis leonurus were successfully produced using high-pressure homogenisation (HPH) on a LAB 40 homogeniser. The particle size was determined for the formulation as well as short-term stability study. The formulation was exposed to Chang liver cells for a glucose uptake study and to INS-1 cells for a chronic insulin release study under normoglycaemic and hyperglycaemic conditions. The particle size of the extract NLC was 220 nm with a PdI of 0.08 after homogenisation at 800 bar. The formulation was stable at the tested temperatures. The extract NLC formulation at 1 µg/ml improved glucose uptake, relative to the control liver cells. Insulin release in INS-1 cells was also elevated under hyperglycaemic conditions when exposed to the NLCs, in comparison with the control untreated cells and the non-formulated extract. The plant extract encapsulated in NLC improved the uptake of glucose and enhanced the insulin sensitivity in vitro, compared to the extract.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

NLC:

Nanostructured lipid carriers

PCS:

Photon correlation spectroscopy

LD:

Laser diffractometry

PdI:

Polydispersity index

HPH:

High-pressure homogenisation

References

  • Ashcroft FM, Proks P, Smith PA, Ämmälä C, Bokvist K, Rorsman P (1994) Stimulus–secretion coupling in pancreatic β cells. J Cell Biochem 55(S1994A):54–65. doi:10.1002/jcb.240550007

    Article  CAS  Google Scholar 

  • Chen Y, Yuan L, Zhou L, Z-h Zhang, Cao W, Wu Q (2012) Effect of cell-penetrating peptide-coated nanostructured lipid carriers on the oral absorption of tripterine. Int J Nanomed 7:4581–4591

    CAS  Google Scholar 

  • Das S, Ng WK, Tan RBH (2012a) Are nanostructured lipid carriers (NLCs) better than solid lipid nanoparticles (SLNs): development, characterizations and comparative evaluations of clotrimazole-loaded SLNs and NLCs? Eur J Pharm Sci 47(1):139–151. doi:10.1016/j.ejps.2012.05.010

    Article  CAS  Google Scholar 

  • Das S, Ng WK, Tan RBH (2012b) Are nanostructured lipid carriers (NLCs) better than solid lipid nanoparticles (SLNs): development, characterizations and comparative evaluations of clotrimazole-loaded SLNs and NLCs? Eur J Pharm Sci 47(1):139–151. doi:10.1016/j.ejps.2012.05.010

    Article  CAS  Google Scholar 

  • Foretz M, Hébrard S, Leclerc J, Zarrinpashneh E, Soty M, Mithieux G, Sakamoto K, Andreelli F, Viollet B (2010) Metformin inhibits hepatic gluconeogenesis in mice independently of the LKB-1/AMPK pathway via a decrease in hepatic energy state. J Clin Invest 120(7):2355–2369. doi:10.1172/jci40671

    Article  CAS  Google Scholar 

  • Freitas C, Müller RH (1998) Spray-drying of solid lipid nanoparticles (SLNTM). Eur J Pharm Biopharm 46(2):145–151. doi:10.1016/S0939-6411(97)00172-0

    Article  CAS  Google Scholar 

  • Gao L, Liu G, Ma J, Wang X, Zhou L, Li X, Wang F (2013) Application of drug nanocrystal technologies on oral drug delivery of poorly soluble drugs. Pharm Res 30(2):307–324. doi:10.1007/s11095-012-0889-z

    Article  CAS  Google Scholar 

  • IDF (2013) International Diabetes Federation. http://www.idf.org/diabetesatlas/introduction. Accessed Oct 24 2013

  • Jin X, Zhang ZH, Li SL, Sun E, Tan XB, Song J, Jia XB (2013) A nanostructured liquid crystalline formulation of 20(S)-protopanaxadiol with improved oral absorption. Fitoterapia 84:64–71. doi:10.1016/j.fitote.2012.09.013

    Article  CAS  Google Scholar 

  • Junghanns J-UAH, Müller RH (2008) Nanocrystal technology, drug delivery and clinical applications. Int J Nanomed 3(3):295–309

    CAS  Google Scholar 

  • Kee NLA, Mnonopi N, Davids H, Naudé RJ, Frost CL (2008) Antithrombotic/anticoagulant and anticancer activities of selected medicinal plants from South Africa. Afr J Biotechnol 7(3):217–223

    Google Scholar 

  • Laonigro G, Lanzetta R, Parulli M, Adolfini M, Mangoni L (1979) Configuration of the diterpene spiroethers from Marrubium vulgare and from Leonotis leonurus. Gaz Chim Ital 109(3/4):145–1150

    CAS  Google Scholar 

  • Leahy JL (2005) Pathogenesis of type 2 diabetes mellitus. Arch Med Res 36(3):197–209. doi:10.1016/j.arcmed.2005.01.003

    Article  CAS  Google Scholar 

  • Light ME, McGraw LJ, Sparg SG, Taylor MN, Erasmus DG, Jager AK, Van Staden J (2002) Investigation of the biological activities of Siphonochilus aethiopicus and the effect of seasonal senescence. S Afr J Bot 68:55–61

    Article  Google Scholar 

  • Mahrouf-Yorgov M, Marie N, Borderie D, Djelidi R, Bonnefont-Rousselot D, Legrand A, Beaudeux JL, Peynet J (2009) Metformin suppresses high glucose-induced poly(adenosine diphosphate-ribose) polymerase overactivation in aortic endothelial cells. Metab Clin Exp 58(4):525–533. doi:10.1016/j.metabol.2008.11.012

    Article  CAS  Google Scholar 

  • Mehnert W, Mäder K (2001) Solid lipid nanoparticles: production, characterization and applications. Adv Drug Deliv Rev 47:165–196

    Article  CAS  Google Scholar 

  • Miller JB, Harris JM, Hobbie EK (2014) Purifying colloidal nanoparticles through ultracentrifugation with implications for interfaces and materials. Langmuir 30(27):7936–7946. doi:10.1021/la404675v

    Article  CAS  Google Scholar 

  • Mitri K, Shegokar R, Gohla S, Anselmi C, Müller RH (2011) Lipid nanocarriers for dermal delivery of lutein: preparation, characterization, stability and performance. Int J Pharm 414(1):267–275

    Article  CAS  Google Scholar 

  • Mnonopi N, Levendal R-A, Davies-Coleman MT, Frost CL (2011a) The cardioprotective effects of marrubiin, a diterpenoid found in Leonotis leonurus extracts. J Ethnopharmacol 138(1):67–75. doi:10.1016/j.jep.2011.08.041

    Article  CAS  Google Scholar 

  • Mnonopi N, Levendal R-A, Davies-Coleman MT, Frost CL (2011b) The cardioprotective effects of marrubiin, a diterpenoid found in Leonotis leonurus extracts. J Ethnopharmacol 138(1):67–75. doi:10.1016/j.jep.2011.08.041

    Article  CAS  Google Scholar 

  • Mnonopi N, Levendal RA, Mzilikazi N, Frost CL (2012a) Marrubiin, a constituent of Leonotis leonurus, alleviates diabetic symptoms. Phytomed 19(6):488–493. doi:10.1016/j.phymed.2011.12.008

    Article  CAS  Google Scholar 

  • Mnonopi N, Levendal RA, Mzilikazi N, Frost CL (2012b) Marrubiin, a constituent of Leonotis leonurus, alleviates diabetic symptoms. Phytomedicine 19(6):488–493. doi:10.1016/j.phymed.2011.12.008

    Article  CAS  Google Scholar 

  • Moschwitzer JP (2013) Drug nanocrystals in the commercial pharmaceutical development process. Int J Pharm 453(1):142–156. doi:10.1016/j.ijpharm.2012.09.034

    Article  Google Scholar 

  • Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65(1–2):55–63

    Article  CAS  Google Scholar 

  • Müller RH, Keck CM (2004) Challenges and solutions for the delivery of biotech drugs—a review of drug nanocrystal technology and lipid nanoparticles. J Biotechnol 113:151–170

    Article  Google Scholar 

  • Müller RH, Gohla S, Keck CM (2011a) State of the art of nanocrystals—special features, production, nanotoxicology aspects and intracellular delivery. Eur J Pharm Biopharm 78(1):1–9. doi:10.1016/j.ejpb.2011.01.007

    Article  Google Scholar 

  • Müller RH, Shegokar R, Keck CM (2011b) 20 years of lipid nanoparticles (SLN and NLC): present state of development and industrial applications. Curr Drug Discov Technol 8(3):207–227

    Article  Google Scholar 

  • Müller RH, Shegokar R, Keck CM (2011c) 20 years of lipid nanoparticles (SLN and NLC): present state of development and industrial applications. Curr Drug Discov Technol 8(3):207–227

    Article  Google Scholar 

  • Preissig CM, Rigby MR (2009) Hyperglycaemia results from beta-cell dysfunction in critically ill children with respiratory and cardiovascular failure: a prospective observational study. Crit Care 13(1):R27. doi:10.1186/cc7732

    Article  Google Scholar 

  • Rabinow B, Kipp J, Papadopoulos P, Wong J, Glosson J, Gass J, Sun C-S, Wielgos T, White R, Cook C, Barker K, Wood K (2007) Itraconazole IV nanosuspension enhances efficacy through altered pharmacokinetics in the rat. Int J Pharm 339(1–2):251–260. doi:10.1016/j.ijpharm.2007.02.030

    Article  CAS  Google Scholar 

  • Radtke M, Souto EB, Müller RH (2005) Nanostructured lipid carriers: a novel generation of solid lipid drug carriers. Pharmaceutical Technol Eur 17(4):45–50

    CAS  Google Scholar 

  • Schmidt S, Jakab M, Jav S, Streif D, Pitschmann A, Zehl M, Purevsuren S, Glasl S, Ritter M (2013) Extracts from Leonurus sibiricus L. increase insulin secretion and proliferation of rat INS-1E insulinoma cells. J Ethnopharmacol 150(1):85–94. doi:10.1016/j.jep.2013.08.013

    Article  CAS  Google Scholar 

  • Skelin M, Rupnik M, Cencic A (2010) Pancreatic beta cell lines and their applications in diabetes mellitus Res. Altex 27(2):105–113

    Article  Google Scholar 

  • Stumvoll M, Goldstein BJ, van Haeften TW (2005) Type 2 diabetes: principles of pathogenesis and therapy. Lancet 365(9467):1333–1346. doi:10.1016/S0140-6736(05)61032-X

    Article  CAS  Google Scholar 

  • Thode K, Müller RH, Kresse M (2000) Two-time window and multiangle photon correlation spectroscopy size and zeta potential analysis—highly sensitive rapid assay for dispersion stability. J Pharm Sci 89(10):1317–1324

    Article  CAS  Google Scholar 

  • Van Wyk B, Van Oudtshoorn B, Gericke B (2000) Medicinal plants of South Africa. Briza Publications, Cape Town p, p 166

    Google Scholar 

  • Wang Y, Zheng Y, Zhang L, Wang Q, Zhang D (2013) Stability of nanosuspensions in drug delivery. J Control Release 172(3):1126–1141. doi:10.1016/j.jconrel.2013.08.006

    Article  CAS  Google Scholar 

  • Wilmot E, Idris I (2014) Early onset type 2 diabetes: risk factors, clinical impact and management. Ther Adv Chronic Dis 5(6):234–244. doi:10.1177/2040622314548679

    Article  Google Scholar 

  • Wu Y, Wang D, Li Y (2014) Nanocrystals from solutions: catalysts. Chem Soc Rev 43(7):2112–2124. doi:10.1039/c3cs60221d

    Article  CAS  Google Scholar 

  • Young PJ (2001) A spoonful of sugar–improving the sensitivity of the glucose oxidase test strip method for detecting subclinical pulmonary aspiration of enteral feed. Anaesth Intensive Care 29(5):539–543

    CAS  Google Scholar 

  • Zhang T, Song YJ, Zhang XY, Wu JY (2014) Synthesis of silver nanostructures by multistep methods. Sensors 14(4):5860–5889. doi:10.3390/s140405860

    Article  Google Scholar 

  • Zozulinska D, Wierusz-Wysocka B (2006) Type 2 Diabetes mellitus as inflammatory disease. Diabetes Res Clin Pract 74:S12–S16

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors acknowledge the financial support of this study by the National Research Foundation (NRF) of South Africa, Nelson Mandela Metropolitan University (NMMU), the Medical Research Council (MRC), as well as the Erasmus Mundus scholarship (Ema2SA) for their effort in the support of establishing a collaboration with Freie University, Berlin. The authors wish to thank the reviewers for their time and constructive input.

Author information

Authors and Affiliations

  1. Department of Biochemistry and Microbiology, Nelson Mandela Metropolitan University, P.O. Box 77000, Port Elizabeth, 6031, South Africa

    Frank Odei-Addo, R-A. Levendal & Carminita Frost

  2. Institute of Pharmacy, Department of Pharmaceutics, Biopharmaceutics and NutriCosmetics, Freie Universität Berlin, Kelchstr. 31, 12169, Berlin, Germany

    Ranjita Shegokar & Rainer H. Müller

Authors
  1. Frank Odei-Addo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ranjita Shegokar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rainer H. Müller
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R-A. Levendal
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Carminita Frost
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Carminita Frost.

Ethics declarations

Conflict of interest

The authors report no conflict of interest for this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Odei-Addo, F., Shegokar, R., Müller, R.H. et al. Nanoformulation of Leonotis leonurus to improve its bioavailability as a potential antidiabetic drug. 3 Biotech 7, 344 (2017). https://doi.org/10.1007/s13205-017-0986-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s13205-017-0986-0

Keywords

Search

Navigation