Solid lipid nanoparticles as a carrier of metformin for transdermal delivery

Authors

  • Rakesh Kumar Sharma Division of CBRN Defence, Institute of Nuclear Medicine and Allied Sciences, Brig. S. K. Mazumdar Road, Delhi 110 054, India.
  • Navneet Sharma Department of Pharmaceutics JSS College of Pharmacy, JSS University Mysore 570 015 Karnatka, India.
  • Sudha Rana Division of CBRN Defence, Institute of Nuclear Medicine and Allied Sciences, Brig. S. K. Mazumdar Road, Delhi 110 054, India
  • Hosakote G. Shivkumar Department of Pharmaceutics JSS College of Pharmacy, JSS University Mysore 570 015 Karnatka, India.

Keywords:

Solid lipid nanoparticles, Metformin, Transdermal patches, In vitro-In vivo studies, Exvivo studies, histopathological studies

Abstract

Worldwide prevalence of type 2 diabetes is increasing with alarming proportions. Metformin is the first-line oral antidiabetic drug of choice for the treatment of type 2 diabetes. The objectives of the present study were to develop Metformin solid lipid nanoparticles (M-SLN) and incorporate it in the transdermal patches. M-SLN was evaluated for Particle size, Zeta potential, Surface morphology by scanning electron microscopy (SEM), Transmission electron microscopy (TEM) and In vitro- In vivo release studies. Patches were evaluated by Ex-vivo skin permeation studies. M-SLN was prepared by solvent diffusion technique using propylene glycol (solvent), polymethacrylic acid (polymer) and Soya lecithin (lipid base). After doing the evaluation of the above mentioned pharmaceutical parameters, M-SLN was loaded in Methocel K100M transdermal patches. Ex-vivo skin permeation studies were conducted on male Wistar ratÊs skin using Franz-type diffusion Cells. The particle size of M-SLN varied among the formulation due to variation in the composition of formulations. Zeta potential of best formulation was found to be +27mV. SEM and TEM indicates discrete spherical structure without aggregation. Drug content was found to be 1.45mg/patch. The ex-vivo permeation studies indicate that the high cumulative amount of drug is permeated from MSLNs. Our study proves the successful delivery of M-SLN from transdermal patch, and Histopathological studies confirmed that the M-SLN transdermal patch only provoked an acceptable modest inflammatory response. These results support the feasibility of developing transdermal metformin for human applications. Thus, transdermal delivery of M-SLN is a safe, painless and cost effective drug delivery system for diabetes patients.

References

Zimmet P, Alberti KG, Shaw J. Global and societal implications of the diabetes epidemic. Nature. 2001; 414(6865):782–787.

Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care. 2004; 27(5):1047–53.

Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC. Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes. 2003; 52(1):102–10.

Stumvoll M, Goldstein BJ, van Haeften TW. Type 2 diabetes principles of pathogenesis and therapy. Lancet. 2005; 365(9467):1333–46.

King H, Aubert R.E, Herman W.H. Global burden of diabetes, 1995/2025: prevalence, numerical estimates, and projections. Diabetes Care. 1998 ; 21:1414-1431

Watanabe M, Yamaoka K, Yokotsuka M, Tango T. Randomized controlled trial of a new dietary education program to prevent type 2 diabetes in a high-risk group of Japanese male workers. Diabetes Care. 2003; 26: 3209–3214.

Voorham J, Haaijer-Ruskamp FM, Stolk RP. et al. for the Groningen Initiative to Analyze Type 2 Diabetes Treatment Group. Influence of elevated cardiometabolic risk factor levels on treatment changes in type 2 diabetes. Diabetes Care. 2008; 31:501–503.

Harris SB, Kapor J, Lank CN. et al. Clinical inertia in patients with T2DM requiring insulin in family practice. Can Fam Physician. 2010; 56:e418 – e424.

Zafar A, Davies M, Azhar A, Khunti K. Clinical inertia in management of T2DM. Prim Care Diabetes. 2010;4:203–207.

David S, Michael F. Preclinical. Evaluation of pharmacokinetic–pharmacodynamic rationale for oral CR metformin formulation. Journal of Controlled Release. 2001;71:107–115.

Vidon N, Chaussade S. Metformin in the digestive tract. Diabetes Research and Clinical Practice.1988;4:223-229.

Wajchenberg BL. beta-cell failure in diabetes and preservation by clinical treatment. Endocr Rev 2007; 28(2):187–218.1.

Van B R, Gorter K, Stolk R, et al. Clinical inertia in general practice: Widespread and related to the outcome of diabetes care. Fam Pract. 2009; 26:428 – 436.

Ebenezer A. N, Terri W. J. Management of type 2 diabetes. Metabolism Clinicall & Experimental.2011; 60:1-23.

Muller R.H, Mader K, Gohla S. Solid lipid nanoparticles (SLN) for controlled drug delivery – a review of the state of the art. Eur. J. Pharm. Biopharm. 2000; 50: 161–177.

Hoffman A, Ziv E. Pharmokinetic considerations of new insulin formulations and routes of administration. ClinPharmacokinet. 1997; 33:285–301.

Mugumu H. Transdermal delivery of Caco3- Nanoparticles Containing Insulin. Diabetes Technology & Therapeutics. 2006; 8 (3): 369-374.

Michael U. A, Yukako Y. Pharmacodynamic–pharmacokinetic profiles of metformin hydrochloride from a mucoadhesive formulation of a polysaccharide with antidiabetic property in streptozotocin-induced diabetic rat models. Biomaterials. 2004; 25: 3041–3048.

Yuancai D, Wai K. N, Shoucang S, Sanggu K, Reginald B.H. T. Solid lipid nanoparticles: Continuous and potential large-scale nanoprecipitation production in static mixers. Colloids and Surfaces B: Biointerfaces. 2012; 94: 68–72.

Sonali V. K, Rajiv V. G, Abdul S, Padma V. D. Self nanoprecipitating preconcentrate of tamoxifen citrate for enhanced bioavailability. International Journal of Pharmaceutics. 2012; 429 (1–2): 104-112.

Katja J, Wolfgang M, Markus D, Heike B, Christoph J, Karsten M. Investigations on the structure of solid lipid nanoparticles (SLN) and oil-loaded solid lipid nanoparticles by photon correlation spectroscopy, field-flow fractionation and transmission electron microscopy. Journal of Controlled Release. 2004; 95 (2, 5):217-227.

Guo J, Ping Q, Zhang L. Transdermal delivery of insulin in mice by using lecithin vesicles as a carrier. Drug Deliv. 2000; 7: 113–116.

Hoffman A, Ziv E. Pharmokinetic considerations of new insulin formulations and routes of administration. Clin Pharmacokinet. 1997; 33:285–301.

Michalowski C.B, Guterres S.S, Costa T. D. Microdialysis for evaluating the entrapment and release of a lipophilic drug from nanoparticles. Journal of Pharmaceutical and Biomedical Analysis. 2004;35:1093-1100.

Kim J.K, Jeong S.P, Chong K.K. Development of a binary lipid nanoparticles formulation of itraconazole for parenteral administration and controlled release. International Journal of Pharmaceutics. 2010; 383(1–2): 209-215.

King M.J, Badea I, Solomon J. Transdermal delivery of insulin from a novel biphasic lipid system in diabetic rats. Diabetes Technol Ther. 2002; 4: 479–488.

Jeffrey E. G, Lynlee L. L, Rokhaya F, Margaret B. Nanoparticles and microparticles for skin drug delivery. Advanced drug delivery Reviews. 2011;63: 470-491.

Pil H. L, Robert C, Veerabahu S. Development of an in silico model for human skin permeation based on a Franz cell skin permeability assay. Bioorganic & Medicinal Chemistry Letters. 2010;20: 69-73.

Ganeshchandra S, Keishiro T, Akira S, Hiroyuki O, Hiroshi T, Kimiko M. In vitro permeation of gold nanoparticles through rat skin and rat intestine: Effect of particle size. Colloids and Surfaces B: Biointerfaces. 2008; 65:1-10.

Mutalik S, Udupa N. Formulation development, in vitro and in vivo evaluation of membrane controlled transdermal systems of glibenclamide. Journal of Pharmacy and Pharmaceutical Sciences. 2005; 1: 26–38.

Kenji S, Yasunori M. Polymers for transdermal drug delivery systems. Journal of Controlled Release. 1994; 29: 177-185.

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Published

2013-06-30

How to Cite

Rakesh Kumar Sharma, Navneet Sharma, Sudha Rana, & Hosakote G. Shivkumar. (2013). Solid lipid nanoparticles as a carrier of metformin for transdermal delivery. International Journal of Drug Delivery, 5(2), 137–145. Retrieved from https://ijdd.arjournals.org/index.php/ijdd/article/view/191

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Original Research Articles