Comparison in the Glucose Response of Flexible Liposomes Loaded with Insulin with the Addition of Different Surfactants in an Experimental Diabetes Model

Author(s): Sara Melisa Arciniegas, Sergio Andres Saavedra, Danaé Balderas, Sara del Carmen Caballero, María Josefa Bernad, Julio Cesar Sánchez, María Isabel Gracia, Héctor Ariel Rico, Dinorah Vargas*

Journal Name: Letters in Drug Design & Discovery

Volume 17 , Issue 6 , 2020

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Abstract:

Background: Insulin has been included in a variety of dosage forms; nevertheless, liposomes have shown protection to degradation and better absorption. The addition of surfactant to liposomes could give the ability to deform and pass through intact membranes, and could increase the stability and the release of the drug.

Introduction: Due to the limitations of the current treatment of insulin in diabetic patients, investigation in alternatives routes has increased. The oral route is the most convenient because of the similarity with the natural secretion of this hormone. The aim was to evaluate the in-vivo effect of fourteen formulations of Insulin-loaded flexible liposomes with different surfactants by oral and subcutaneous routes.

Methods: Fourteen formulations of insulin were obtained with the addition of different surfactants. Size distribution, polydispersion index and Z potential were obtained for all formulations. In-vivo tests were performed in rats induced with experimental diabetes with streptozotocin, and glucose curves were obtained during 480 minutes.

Results: All formulations by the subcutaneous route caused an optimal reduction in glucose levels. However, the addition of Brij L23 produced a better reduction, lasting for 420 minutes. By the oral route, the reduction of glucose did not reach the normal levels, but the addition of Poloxamer 407 and Brij S10 showed the best reduction in the glucose levels by this route.

Conclusion: The addition of surfactants to the lipid structure can modify the release of the insulin by different routes of administration, but this behavior depends on the characteristics of the surfactant, such as the melting phase transition temperature of the lipid bilayer.

Keywords: Tensoactive, insulin, lipid vesicles, diabetes, nanocarrier, liposome.

[1]
Peppas NA, Kavimandan NJ. Nanoscale analysis of protein and peptide absorption: insulin absorption using complexation and pH-sensitive hydrogels as delivery vehicles. Eur J Pharm Sci 2006; 29(3-4): 183-97.
[http://dx.doi.org/10.1016/j.ejps.2006.04.014] [PMID: 16777391]
[2]
Mahato RI, Narang AS, Thoma L, Miller DD. Emerging trends in oral delivery of peptide and protein drugs. Crit Rev Ther Drug Carrier Syst 2003; 20(2-3): 153-214.
[http://dx.doi.org/10.1615/CritRevTherDrugCarrierSyst.v20.i23.30] [PMID: 14584523]
[3]
Yun Y, Cho YW, Park K. Nanoparticles for oral delivery: targeted nanoparticles with peptidic ligands for oral protein delivery. Adv Drug Deliv Rev 2013; 65(6): 822-32.
[http://dx.doi.org/10.1016/j.addr.2012.10.007] [PMID: 23123292]
[4]
Cevc G, Gebauer D, Stieber J, Schätzlein A, Blume G. Ultraflexible vesicles, Transfersomes, have an extremely low pore penetration resistance and transport therapeutic amounts of insulin across the intact mammalian skin. Biochim Biophys Acta 1998; 1368(2): 201-15.
[http://dx.doi.org/10.1016/S0005-2736(97)00177-6] [PMID: 9459598]
[5]
Malakar J, Sen SO, Nayak AK, Sen KK. Formulation, optimization and evaluation of transferosomal gel for transdermal insulin delivery. Saudi Pharm J 2012; 20(4): 355-63.
[http://dx.doi.org/10.1016/j.jsps.2012.02.001] [PMID: 23960810]
[6]
Fazel M, Daeihameda M, Osoulia M, Almasia A, Haeria A, Dadashzadeha S. Preparation, In-Vitro Characterization and Pharmacokinetic Evaluation of Brij Decorated Doxorubicin Liposomes as a Po-tential Nanocarrier for Cancer Therapy. Iran. J. Pharm. Res, 2018; 17(Special Issue 2): 33-43.
[7]
Sonia T, Sharma C. Oral insulin delivery. 1st ed. Woodhead Publishing United Kingdom In: 2014.
[8]
Cevc G, Schätzlein A, Richardsen H. Ultradeformable lipid vesicles can penetrate the skin and other semi-permeable barriers unfragmented. Evidence from double label CLSM experiments and direct size measurements. Biochim Biophys Acta 2002; 1564(1): 21-30.
[http://dx.doi.org/10.1016/S0005-2736(02)00401-7] [PMID: 12100992]
[9]
Mezei M. Liposomes and the skinLiposomes in drug delivery; Gregoridadis, G; Florence, AT Patel, H, Eds; Harwood Academic Publishers:. Switzerland 1993; pp. 24-135.
[10]
Cevc G, Blume G. New, highly efficient formulation of diclofenac for the topical, transdermal administration in ultradeformable drug carriers, Transfersomes. Biochim Biophys Acta 2001; 1514(2): 191-205.
[http://dx.doi.org/10.1016/S0005-2736(01)00369-8] [PMID: 11557020]
[11]
Cevc G. Transdermal drug delivery of insulin with ultradeformable carriers. Clin Pharmacokinet 2003; 42(5): 461-74.
[http://dx.doi.org/10.2165/00003088-200342050-00004] [PMID: 12739984]
[12]
Rajan R, Jose S, Mukund VP, Vasudevan DT. Transferosomes - A vesicular transdermal delivery system for enhanced drug permeation. J Adv Pharm Technol Res 2011; 2(3): 138-43.
[http://dx.doi.org/10.4103/2231-4040.85524] [PMID: 22171309]
[13]
Arciniegas S. M: Bernad, M.J.; Lopez, R.; Torres, R.; Caballero, S.C.; Vargas, D. In-vitro and In-vivo Profiles and Characterization of Insulin Nanocarriers Based in Flexible Liposomes Designed for Oral Administration. Lett Drug Des Discov 2019; 16(1)
[14]
Mozafari MR. Liposomes: an overview of manufacturing techniques. Cell Mol Biol Lett 2005; 10(4): 711-9.
[PMID: 16341279]
[15]
Park SJ, Choi SG, Davaa E, Park JS. Encapsulation enhancement and stabilization of insulin in cationic liposomes. Int J Pharm 2011; 415(1-2): 267-72.
[http://dx.doi.org/10.1016/j.ijpharm.2011.05.061] [PMID: 21645598]
[16]
Szkudelski T. The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiol Res 2001; 50(6): 537-46.
[PMID: 11829314]
[17]
Trinder P. Determination of glucose in blood using glucose oxidase with an alternative oxygen receptor. Ann Clin Biochem 1969; 6: 24-37.
[http://dx.doi.org/10.1177/000456326900600108]
[18]
Malvern. Technical Notes [Online]. Malvern Instruments Lim-ited. http://www.malvern.com/en/support/resource-center/technical-notes/TN101104IntensityVolumeNumber.aspx
[19]
Wriedt, T. Mie Theory, A review. InThe Mie Theory. Basics and applications. Germany, Springer Series in Optical Science; Hergert, W.; Wriedt, T., Eds.; 2012, 169, pp. 53-79. In:
[20]
Badran M. Formulation and in vitro evaluation of flufenamic acid loaded deformable liposome for improved skin delivery. Dig J Nanomater Biostruct 2014; 9: 83-91.
[21]
Chen M, Liu X, Fahr A. Skin penetration and deposition of carboxyfluorescein and temoporfin from different lipid vesicular systems: In vitro study with finite and infinite dosage application. Int J Pharm 2011; 408(1-2): 223-34.
[http://dx.doi.org/10.1016/j.ijpharm.2011.02.006] [PMID: 21316430]
[22]
Putri DC, Dwiastuti R, Marchaban M, Nugroho AK. Optimization of mixing temperature and sonication duration in liposome preparation. J Pharm Sci Commun 2017; 14: 79-85.
[http://dx.doi.org/10.24071/jpsc.142728]
[23]
Patel HM, Ryman BE. Oral administration of insulin by encapsulation within liposomes. FEBS Lett 1976; 62(1): 60-3.
[http://dx.doi.org/10.1016/0014-5793(76)80016-6] [PMID: 129340]
[24]
Spangler RS. Insulin administration via liposomes. Diabetes Care 1990; 13(9): 911-22.
[http://dx.doi.org/10.2337/diacare.13.9.911] [PMID: 2226109]
[25]
Choudhari KB, Labhasetwar V, Dorle AK. Liposomes as a carrier for oral administration of insulin: effect of formulation factors. J Microencapsul 1994; 11(3): 319-25.
[http://dx.doi.org/10.3109/02652049409040461] [PMID: 8064555]
[26]
Mustata G, Dinh SM. Approaches to oral drug delivery for challenging molecules. Crit Rev Ther Drug Carrier Syst 2006; 23(2): 111-35.
[http://dx.doi.org/10.1615/CritRevTherDrugCarrierSyst.v23.i2.20] [PMID: 16952274]
[27]
Bendayan M, Ziv E, Gingras D, Ben-Sasson R, Bar-On H, Kidron M. Biochemical and morpho-cytochemical evidence for the intestinal absorption of insulin in control and diabetic rats. Comparison between the effectiveness of duodenal and colon mucosa. Diabetologia 1994; 37(2): 119-26.
[http://dx.doi.org/10.1007/s001250050081] [PMID: 8163044]
[28]
Khan MA, Agarwal V. Composition and method for preparation of an oral dual con-trolled release formulation of a protein and inhibitor. US Patent, 2003, 20, 220-254
[29]
TenHoor C, Dressman J. Oral absorption of peptides and proteins. STP Pharma Sci 1992; 2: 301-12.
[30]
Patel HM, Stevenson RW, Parsons JA, Ryman BE. Use of liposomes to aid intestinal absorption of entrapped insulin in normal and diabetic dogs. Biochim Biophys Acta 1982; 716(2): 188-93.
[http://dx.doi.org/10.1016/0304-4165(82)90267-7] [PMID: 7046805]
[31]
Owens DR, Zinman B, Bolli G. Alternative routes of insulin delivery. Diabet Med 2003; 20(11): 886-98.
[http://dx.doi.org/10.1046/j.1464-5491.2003.01076.x] [PMID: 14632713]
[32]
Lai SK, Wang YY, Hanes J. Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues. Adv Drug Deliv Rev 2009; 61(2): 158-71.
[http://dx.doi.org/10.1016/j.addr.2008.11.002] [PMID: 19133304]
[33]
Değim IT, Gümüşel B, Değim Z, Ozçelikay T, Tay A, Güner S. Oral administration of liposomal insulin. J Nanosci Nanotechnol 2006; 6(9-10): 2945-9.
[http://dx.doi.org/10.1166/jnn.2006.416] [PMID: 17048502]
[34]
Sipai Altaf Bhai M, Vandana D, Mamatha Y, Prasanth V. Liposomes:An overview. J Pharm Sci Innov 2012; 1(1): 13-21.
[35]
Vijayakumar M, Kosuru R, Vuddanda P, Singh KS, Singh S. Trans resveratrol loaded DSPE PEG 2000 coated liposomes: An evidence for prolonged systemic circulation and passive brain targeting. J Drug Deliv Sci Technol 2016; 33: 125-35.
[http://dx.doi.org/10.1016/j.jddst.2016.02.009]
[37]
Martins S, Sarmento B, Ferreira DC, Souto EB. Lipid-based colloidal carriers for peptide and protein delivery--liposomes versus lipid nanoparticles. Int J Nanomedicine 2007; 2(4): 595-607.
[PMID: 18203427]
[38]
Zhang P, Huang Y, Makhov AM, Gao X, Zhang P, Li S. Characterization of spherulites as a lipidic carrier for low and high molecular weight agents. Pharm Res 2013; 30(6): 1525-35.
[http://dx.doi.org/10.1007/s11095-013-0990-y] [PMID: 23579481]
[39]
Kneidl B, Peller M, Winter G, Lindner LH, Hossann M. Thermosensitive liposomal drug delivery systems: state of the art review. Int J Nanomedicine 2014; 9: 4387-98.
[PMID: 25258529]
[40]
Tagami T, Ernsting MJ, Li SD. Optimization of a novel and improved thermosensitive liposome formulated with DPPC and a Brij surfactant using a robust in vitro system. J Control Release 2011; 154(3): 290-7.
[http://dx.doi.org/10.1016/j.jconrel.2011.05.020] [PMID: 21640149]
[41]
Thakur R, Das A, Chakraborty A. The fate of anticancer drug, ellipticine in DPPC and DMPC liposomes upon interaction with HSA: a photophysical approach. J Photochem Photobiol B 2014; 130(5): 122-31.
[http://dx.doi.org/10.1016/j.jphotobiol.2013.10.016] [PMID: 24322006]
[42]
Tian JL, Ke X, Chen Z, Wang CJ, Zhang Y, Zhong TC. Melittin liposomes surface modified with poloxamer 188: in vitro characterization and in vivo evaluation. Pharmazie 2011; 66(5): 362-7.
[PMID: 21699070]
[43]
Grohmann F, Csempesz F, Szogyi M. Stabilization of small unilamellar DMPC-liposomes by uncharged polymers. Colloid Polym Sci 1998; 276: 66-71.
[http://dx.doi.org/10.1007/s003960050210]
[44]
Zhang W, Wang G, See E, et al. Shaw, J.P.; Baguley, B.C.; Liu, J.; Amirapu, S.; Wu, Z. Post-insertion of poloxamer 188 strengthened liposomal membrane and reduced drug irritancy and in vivo precipitation, superior to PEGylation. J Control Release 2015; 203: 161-9.
[http://dx.doi.org/10.1016/j.jconrel.2015.02.026] [PMID: 25701612]
[45]
Lasic DD. Liposomes from physics to applications. 1st ed. ElSevier Science BV Amsterdam 1993.
[46]
Mozafari MR, Reed CJ, Rostron C. Cytotoxicity evaluation of anionic nanoliposomes and nanolipoplexes prepared by the heating method without employing volatile solvents and detergents. Pharmazie 2007; 62(3): 205-9.
[PMID: 17416197]
[47]
Arciniegas SM, Bernad MJ, Caballero S, Vargas D. Glucose Response in Animals Induced with experimental Diabetes Type 1 after Treatment with Human Insulin Exposed To High Temperatures. Transylv Rev 2017; XXV(23): 6191-6.


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Article Details

VOLUME: 17
ISSUE: 6
Year: 2020
Page: [787 - 798]
Pages: 12
DOI: 10.2174/1570180816666191024102231

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