Generic placeholder image

Recent Patents on Nanotechnology

Editor-in-Chief

ISSN (Print): 1872-2105
ISSN (Online): 2212-4020

Research Article

Enhanced Solubility and Permeability of Naringenin Across Non-Everted Sacs of Rat Small Intestine by Lipid Nanocapsules

Author(s): Hamed Vakilzadeh, Jaleh Varshosaz* and Sahel Soghrati

Volume 15, Issue 1, 2021

Published on: 31 July, 2020

Page: [55 - 69] Pages: 15

DOI: 10.2174/1872210514666200731181130

Price: $65

Abstract

Background: Naringenin (NRG) has many health benefits, including; anti-atherogenic, antiinflammatory, antitumor, and anticancer activity, as well as improvement of lipid metabolism. However, its use is limited due to its low solubility and bioavailability.

Objectives: The aim of the present patent study was the preparation and optimization of NRG loaded Novel Lipid Nanocapsules (LNCs) for the improvement of NRG solubility and gut permeability.

Methods: Studied variables included; Solutol® HS15 and NRG concentration and the ratio of cold diluent water to primary emulsion. The storage stability of the LNCs was evaluated for 32 days and thermal analyses were conducted by Differential Scanning Calorimetry (DSC). The antioxidant properties of the NRG in LNCs were studied by measuring the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity. The enhancement of permeation of NRG by the LNCs from the intestine was evaluated by the non-everted gut sac method.

Results: The optimized NRG-LNCs had a hydrodynamic diameter of 29.41±1.25 nm, a low polydispersity index, and high entrapment efficiency of 99.25±2.31%. The LNCs could retain NRG radical scavenging activity, showed good storage stability, and significantly improved NRG solubility (69 fold) and permeation through non-everted rat intestinal sac (4.33 fold).

Conclusion: LNCs of NGR enhance solubility and intestinal permeability of this flavonoid and may be useful in the improvement of its bioavailability.

Keywords: Naringenin, lipid nanocapsules, gut permeation, solubility, non-everted intestinal sac, polyphenols, hydrolysis.

Graphical Abstract

[1]
Handford CE, Dean M, Henchion M, Spence M, Elliott CT, Campbell K. Implications of nanotechnology for the agri-food industry: Opportunities, benefits and risks. Trends Food Sci Technol 2014; 40: 226-41.
[http://dx.doi.org/10.1016/j.tifs.2014.09.007]
[2]
Munin A, Edwards-Lévy F. Encapsulation of natural polyphenolic compounds; A review. Pharmaceutics 2011; 3(4): 793-829.
[http://dx.doi.org/10.3390/pharmaceutics3040793 ] [PMID: 24309309]
[3]
Yen FL, Wu TH, Lin LT, Cham TM, Lin CC. Naringenin-loaded nanoparticles improve the physicochemical properties and the hepatoprotective effects of naringenin in orally-administered rats with CCl(4)-induced acute liver failure. Pharm Res 2009; 26(4): 893-902.
[http://dx.doi.org/10.1007/s11095-008-9791-0 ] [PMID: 19034626]
[4]
Lin WY, Guang Z, Cai ZX. Method for preparing naringenin by organic acid hydrolysis of naringin. CN Patent 104829579A . 2015.
[5]
Walton SK, Olcese GE. Sweet taste improving compositions including naringenin and steviol glycosides. US Patent 20190200645,. 2019.
[6]
Liang W, Zhang C, Zeng W, Zhang C, Wang L. Application of naringenin and naringin in tumor radiotherapy. CN Patent 104940932A,. 2015.
[7]
Zhang C, Zeng W, Liang W, Jin L, Wei X, Huan F. Application of flavonoid small molecule medicine in anti-inflammation and associated diseases. CN Patent, 102302483A. 2011.
[8]
Mirko B. Pharmaceutical composition and method of use. US Patent 5145839. 1992.
[9]
Kong R, Zhao H, Wong STC. Compositions and methods for selectively inhibiting intestinal carboxylesterase 2 enzyme activity. US Patent 10314811,. 2019.
[10]
Liu J, Lu H, Zhang H, et al. Applications of naringenin and naringin as signal pathway inhibitor of transforming growth factor-beta 1. CN Patent 101322700B,. 2008.
[11]
Su W, Wang Y, Fang T, Peng W, Wu Z. Uses of naringenin, naringin and salts thereof as expectorants in the treatment of cough, and compositions thereof. WO Patent 2004064848A1, . 2004.
[12]
Su W, Wang Y, Wu Z. 8-substituted naringenin derivative and use thereof. US Patent 20160130245 2016; 6..
[13]
Bok SH, Jeong TS, Bae KH, et al. Naringin and naringenin as inhibitors of acyl CoA-cholesterol-o-acyltransferase. US Patent 6165984A,. 2000.
[14]
Ahn JA, Bae KH, Bok SH, et al. Naringin and naringenin as inhibitor of acyl coa-cholesterol-o-acyltransferase, inhibitor of macrophage- lipid complex accumulation on the arterial wall and preventive or treating agent for hepatic diseases. EP Patent 1032381A1,. 2003.
[15]
Kong W, Cui Q, Zheng J, Liu Z, Yu F. Use of naringenin in preparing drugs for preventing and/or treatment abdominal aortic aneurysm. US Patent 9669005,. 2017.
[16]
Burger AR, Granger SP, Scott IR. Skin care compositions containing naringenin and/or quercetin and a retinoid. US Patent 5665367,. 1997.
[17]
Bok SH, Jeong TS, Bae KH, et al. Method for lowering blood glucose level by the administration of bioflavonoid. US Patent 6096364,. 2000.
[18]
Shpigelman A, Shoham Y, Israeli-Lev G, Livney YD. β-Lactoglobulin–naringenin complexes: Nano-vehicles for the delivery of a hydrophobic nutraceutical. Food Hydrocoll 2014; 40: 214-24.
[http://dx.doi.org/10.1016/j.foodhyd.2014.02.023]
[19]
Krishnakumar N, Sulfikkarali N. RajendraPrasad N, Karthikeyan S. Enhanced anticancer activity of naringenin-loaded nanoparticles in human cervical (HeLa) cancer cells. Biomed Prev Nutr 2011; 1: 223-31.
[http://dx.doi.org/10.1016/j.bionut.2011.09.003]
[20]
Nait CM, Al Ahmad A, Peluso J, Muller CD, Ubeaud G. Quercetin and naringenin transport across human intestinal Caco-2 cells. J Pharm Pharmacol 2009; 61(11): 1473-83.
[http://dx.doi.org/10.1211/jpp.61.11.0006] [PMID: 19903372]
[21]
Sekhon BS. Food nanotechnology - An overview. Nanotechnol Sci Appl 2010; 3: 1-15.
[PMID: 24198465]
[22]
Shanker R, Shivendu R, Nandita D, Arkadyuti RC, Samuel SM. Chidambaram Ramalingam. Nanoscience and nanotechnologies in food industries: Opportunities and research trends. J Nanopart Res 2014; 16: 1-23.
[23]
Ghorbanzade T, Jafari SM, Akhavan S, Hadavi R. Nano-encapsulation of fish oil in nano-liposomes and its application in fortification of yogurt. Food Chem 2017; 216: 146-52.
[http://dx.doi.org/10.1016/j.foodchem.2016.08.022 ] [PMID: 27596403]
[24]
Ji P, Yu T, Liu Y, et al. Naringenin-loaded solid lipid nanoparticles: preparation, controlled delivery, cellular uptake, and pulmonary pharmacokinetics. Drug Des Devel Ther 2016; 10: 911-25.
[PMID: 27041995]
[25]
Virk P, Al-Ghamdi NAM, Awad MAG, Wagealla MAE, Hendi AA, Al Hassan LSM. Synthesis of naringenin nanoparticles. US Patent 9622984B1,. 2017.
[26]
Davidov-Pardo G, McClements DJ. Resveratrol encapsulation: Designing delivery systems to overcome solubility, stability and bioavailability issues. Trends Food Sci Technol 2014; 38: 88-103.
[http://dx.doi.org/10.1016/j.tifs.2014.05.003]
[27]
Neo YP, Ray S, Jin J, et al. Encapsulation of food grade antioxidant in natural biopolymer by electrospinning technique: A physicochemical study based on zein-gallic acid system. Food Chem 2013; 136(2): 1013-21.
[http://dx.doi.org/10.1016/j.foodchem.2012.09.010 ] [PMID: 23122157]
[28]
Heurtault B, Saulnier P, Pech B, et al. The influence of lipid nanocapsule composition on their size distribution. Eur J Pharm Sci 2003; 18(1): 55-61.
[http://dx.doi.org/10.1016/S0928-0987(02)00241-5 ] [PMID: 12554073]
[29]
Roger E, Lagarce F, Benoit JP. The gastrointestinal stability of lipid nanocapsules. Int J Pharm 2009; 379(2): 260-5.
[http://dx.doi.org/10.1016/j.ijpharm.2009.05.069] [PMID: 19524655]
[30]
Kuentz M. Drug absorption modeling as a tool to define the strategy in clinical formulation development. AAPS J 2008; 10(3): 473-9.
[http://dx.doi.org/10.1208/s12248-008-9054-3] [PMID: 18751901]
[31]
Pouton CW. Lipid formulations for oral administration of drugs: Non-emulsifying, self-emulsifying and ‘self-microemulsifying’ drug delivery systems. Eur J Pharm Sci 2000; 11(Suppl. 2): S93-8.
[http://dx.doi.org/10.1016/S0928-0987(00)00167-6 ] [PMID: 11033431]
[32]
Abdel-Mottaleb MM, Neumann D, Lamprecht A. In vitro drug release mechanism from Lipid Nanocapsules (LNC). Int J Pharm 2010; 390(2): 208-13.
[http://dx.doi.org/10.1016/j.ijpharm.2010.02.001 ] [PMID: 20149853]
[33]
Eissa MM, El-Moslemany RM, Ramadan AA, Amer EI, El-Azzouni MZ, El-Khordagui LK. Miltefosine lipid nanocapsules for single dose oral treatment of schistosomiasis mansoni: A preclinical study. PLoS One 2015; 10(11)e0141788
[http://dx.doi.org/10.1371/journal.pone.0141788] [PMID: 26574746]
[34]
Ramadan A, Lagarce F, Tessier-Marteau A, et al. Oral fondaparinux: Use of lipid nanocapsules as nanocarriers and in vivo pharmacokinetic study. Int J Nanomedicine 2011; 6: 2941-51.
[PMID: 22162653]
[35]
Barras A, Mezzetti A, Richard A, et al. Formulation and characterization of polyphenol-loaded lipid nanocapsules. Int J Pharm 2009; 379(2): 270-7.
[http://dx.doi.org/10.1016/j.ijpharm.2009.05.054 ] [PMID: 19501139]
[36]
Kiani A, Fathi M, Ghasemi SM. Production of novel vitamin D3 loaded lipid nanocapsules for milk fortification. Int J Food Prop 2017; 20: 2466-76.
[http://dx.doi.org/10.1080/10942912.2016.1240690]
[37]
Ezz MK, Ibrahim NK, Said MM, Farrag MA. The beneficial radioprotective effect of tomato seed oil against gamma radiation-induced damage in male rats. J Diet Suppl 2018; 15(6): 923-38.
[http://dx.doi.org/10.1080/19390211.2017.1406427 ] [PMID: 29336631]
[38]
Yi J, Lam TI, Yokoyama W, Cheng LW, Zhong F. Beta-carotene encapsulated in food protein nanoparticles reduces peroxyl radical oxidation in Caco-2 cells. Food Hydrocoll 2015; 43: 31-40.
[http://dx.doi.org/10.1016/j.foodhyd.2014.04.028]
[39]
Santas J, Codony R, Rafecas M. Phytosterols: Beneficial EffectsNatural product. 1st ed. Berlin: Springer 2013; pp. 3437-64.
[http://dx.doi.org/10.1007/978-3-642-22144-6_149]
[40]
Huynh NT, Passirani C, Saulnier P, Benoît JP. Lipid nanocapsules: a new platform for nanomedicine. Int J Pharm 2009; 379(2): 201-9.
[http://dx.doi.org/10.1016/j.ijpharm.2009.04.026 ] [PMID: 19409468]
[41]
Heurtault B, Saulnier P, Pech B, Proust JE, Benoit JP. A novel phase inversion-based process for the preparation of lipid nanocarriers. Pharm Res 2002; 19(6): 875-80.
[http://dx.doi.org/10.1023/A:1016121319668] [PMID: 12134960]
[42]
Ding B, Chen H, Wang C, Zhai Y, Zhai G. Preparation and in vitro evaluation of apigenin loaded lipid nanocapsules. J Nanosci Nanotechnol 2013; 13(10): 6546-52.
[http://dx.doi.org/10.1166/jnn.2013.7763] [PMID: 24245113]
[43]
Hirsjärvi S, Bastiat G, Saulnier P, Benoît JP. Evaluation of surface deformability of lipid nanocapsules by drop tensiometer technique, and its experimental assessment by dialysis and tangential flow filtration. Int J Pharm 2012; 434(1-2): 460-7.
[http://dx.doi.org/10.1016/j.ijpharm.2012.06.019] [PMID: 22698864]
[44]
Tamjidi F, Shahedi M, Varshosaz J, Nasirpour A. Nanostructured Lipid Carriers (NLC): A potential delivery system for bioactive food molecules. Innov Food Sci Emerg Technol 2013; 19: 29-43.
[http://dx.doi.org/10.1016/j.ifset.2013.03.002]
[45]
Hategekimana J, Masamba KG, Ma J, Zhong F. Encapsulation of vitamin E: Effect of physicochemical properties of wall material on retention and stability. Carbohydr Polym 2015; 124: 172-9.
[http://dx.doi.org/10.1016/j.carbpol.2015.01.060 ] [PMID: 25839808]
[46]
Safwat S, Hathout RM, Ishak RA, Mortada ND. Augmented simvastatin cytotoxicity using optimized lipid nanocapsules: A potential for breast cancer treatment. J Liposome Res 2017; 27(1): 1-10.
[http://dx.doi.org/10.3109/08982104.2015.1137313 ] [PMID: 26872624]
[47]
Hirsjärvi S, Dufort S, Gravier J, et al. Influence of size, surface coating and fine chemical composition on the in vitro reactivity and in vivo biodistribution of lipid nanocapsules versus lipid nanoemulsions in cancer models. Nanomedicine (Lond) 2013; 9(3): 375-87.
[http://dx.doi.org/10.1016/j.nano.2012.08.005] [PMID: 22960195]
[48]
Allard E, Passirani C, Garcion E, et al. Lipid nanocapsules loaded with an organometallic tamoxifen derivative as a novel drug-carrier system for experimental malignant gliomas. J Control Release 2008; 130(2): 146-53.
[http://dx.doi.org/10.1016/j.jconrel.2008.05.027] [PMID: 18582507]
[49]
Lamprecht A, Saumet JL, Roux J, Benoit JP. Lipid nanocarriers as drug delivery system for ibuprofen in pain treatment. Int J Pharm 2004; 278(2): 407-14.
[http://dx.doi.org/10.1016/j.ijpharm.2004.03.018] [PMID: 15196644]
[50]
Lamprecht A, Bouligand Y, Benoit JP. New lipid nanocapsules exhibit sustained release properties for amiodarone. J Control Release 2002; 84(1-2): 59-68.
[http://dx.doi.org/10.1016/S0168-3659(02)00258-4 ] [PMID: 12399168]
[51]
Vonarbourg A, Saulnier P, Passirani C, Benoit JP. Electrokinetic properties of noncharged lipid nanocapsules: Influence of the dipolar distribution at the interface. Electrophoresis 2005; 26(11): 2066-75.
[http://dx.doi.org/10.1002/elps.200410145] [PMID: 15852355]
[52]
Ohshima H. Electrokinetics of soft particles. Colloid Polym Sci 2007; 285: 1411-21.
[http://dx.doi.org/10.1007/s00396-007-1740-7]
[53]
Jumaa M, Müller BW. Parenteral emulsions stabilized with a mixture of phospholipids and PEG-660-12-hydroxy-stearate: Evaluation of accelerated and long-term stability. Eur J Pharm Biopharm 2002; 54(2): 207-12.
[http://dx.doi.org/10.1016/S0939-6411(02)00057-7 ] [PMID: 12191693]
[54]
Mazzarino L, Dora CL, Bellettini IC, Minatti E, Cardoso SG, Lemos-Senna E. Curcumin-loaded polymeric and lipid nanocapsules: preparation, characterization and chemical stability evaluation. Lat Am J Pharm 2010; 29: 933-40.
[55]
Peltier S, Oger JM, Lagarce F, Couet W, Benoît JP. Enhanced oral paclitaxel bioavailability after administration of paclitaxel-loaded lipid nanocapsules. Pharm Res 2006; 23(6): 1243-50.
[http://dx.doi.org/10.1007/s11095-006-0022-2] [PMID: 16715372]
[56]
Zhu Z. Effects of amphiphilic diblock copolymer on drug nanoparticle formation and stability. Biomaterials 2013; 34(38): 10238-48.
[http://dx.doi.org/10.1016/j.biomaterials.2013.09.015 ] [PMID: 24070569]
[57]
Kirby BJ. Micro-and nanoscale fluid mechanics: Transport in microfluidic devices. 1st ed. Newyork: Cambridge university press 2010; pp. 199-225.
[58]
Vakilzadeh H, Varshosaz J, Minaiyan M. Pulmonary delivery of triptorelin loaded in pluronic based nanomicelles in rat model. Curr Drug Deliv 2018; 15(5): 630-40.
[http://dx.doi.org/10.2174/1567201815666180209113735 ] [PMID: 29424314]
[59]
Xu XR, Yu HT, Hang L, Shao Y, Ding SH, Yang XW. Preparation of naringenin/β-cyclodextrin complex and its more potent alleviative effect on choroidal neovascularization in rats. BioMed Res Int 2014; 2014623509
[http://dx.doi.org/10.1155/2014/623509] [PMID: 24795889]
[60]
Saberi AH, Fang Y, McClements DJ. Effect of glycerol on formation, stability, and properties of vitamin-E enriched nanoemulsions produced using spontaneous emulsification. J Colloid Interface Sci 2013; 411: 105-13.
[http://dx.doi.org/10.1016/j.jcis.2013.08.041] [PMID: 24050638]
[61]
Hunter RJ. Charge and Potential Distribution at Interfaces Zeta potential in colloid science. 1st ed. Massachusetts: Academic press 1988; pp. 11-58.
[62]
Widegren J, Bergström L. Electrostatic stabilization of ultrafine titania in ethanol. J Am Ceram Soc 2002; 85: 523-8.
[http://dx.doi.org/10.1111/j.1151-2916.2002.tb00127.x]
[63]
Jiang J, Oberdörster G, Biswas P. Characterization of size, surface charge, and agglomeration state of nanoparticle dispersions for toxicological studies. J Nanopart Res 2009; 11: 77-89.
[http://dx.doi.org/10.1007/s11051-008-9446-4]
[64]
Ban C, Park SJ, Lim S, Choi SJ, Choi YJ. Improving flavonoid bioaccessibility using an edible oil-based lipid nanoparticle for oral delivery. J Agric Food Chem 2015; 63(21): 5266-72.
[http://dx.doi.org/10.1021/acs.jafc.5b01495 ] [PMID: 25976277]
[65]
Chaurasia S, Patel RR, Vure P, Mishra B. Oral naringenin nanocarriers: Fabrication, optimization, pharmacokinetic and chemotherapeutic efficacy assessments. Nanomedicine (Lond) 2017; 12(11): 1243-60.
[http://dx.doi.org/10.2217/nnm-2016-0436] [PMID: 28593828]
[66]
Chen C, Jie X, Ou Y, et al. Nanoliposome improves inhibitory effects of naringenin on nonalcoholic fatty liver disease in mice. Nanomedicine (Lond) 2017; 12(15): 1791-800.
[http://dx.doi.org/10.2217/nnm-2017-0119] [PMID: 28718703]
[67]
Ee SL, Duan X, Liew J, Nguyen QD. Droplet size and stability of nano-emulsions produced by the temperature phase inversion method. Chem Eng J 2008; 140: 626-31.
[http://dx.doi.org/10.1016/j.cej.2007.12.016]
[68]
Vági E, Simándi B, Vásárhelyiné KP, et al. Supercritical carbon dioxide extraction of carotenoids, tocopherols and sitosterols from industrial tomato by-products. J Supercrit Fluids 2007; 40: 218-26.
[http://dx.doi.org/10.1016/j.supflu.2006.05.009]
[69]
Jia L. Nanoparticle formulation increases oral bioavailability of poorly soluble drugs: Approaches, experimental evidences and theory. Curr Nanosci 2005; 1(3): 237-43.
[http://dx.doi.org/10.2174/157341305774642939] [PMID: 19865587]
[70]
Varshosaz J, Taymouri S, Jahanian-Najafabadi A, Alizadeh A. Efavirenz oral delivery via lipid nanocapsules: Formulation, optimisation, and ex-vivo gut permeation study. IET Nanobiotechnology 2018; 12: 795-806.
[http://dx.doi.org/10.1049/iet-nbt.2018.0006]
[71]
Roger E, Gimel JC, Bensley C, Klymchenko AS, Benoit JP. Lipid nanocapsules maintain full integrity after crossing a human intestinal epithelium model. J Control Release 2017; 253: 11-8.
[http://dx.doi.org/10.1016/j.jconrel.2017.03.005 ] [PMID: 28274740]
[72]
Jain AS, Makhija DT, Goel PN, et al. Docetaxel in cationic lipid nanocapsules for enhanced in vivo activity. Pharm Dev Technol 2016; 21(1): 76-85.
[http://dx.doi.org/10.3109/10837450.2014.971374 ] [PMID: 25329444]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy