Characterization and distribution of niosomes containing ursolic acid coated with chitosan layer

Andang Miatmoko , Shofi Ameliah Safitri, Fayruz Aquila, Devy Maulidya Cahyani, Berlian Sarasitha Hariawan, Eryk Hendrianto, Esti Hendradi, Retno Sari

Abstract


Background and purpose: Ursolic acid (UA) exhibits anti-hepatocarcinoma and hepatoprotective activities, thus promising as an effective oral cancer therapy. However, its poor solubility and permeability lead to low oral bioavailability. In this study, we evaluated the effect of different ratios of Span® 60-cholesterol-UA and also chitosan addition on physical characteristics and stability of niosomes to improve oral biodistribution.

Experimental approach: UA niosomes (Nio-UA) were composed of Span® 60-cholesterol-UA at different molar ratios and prepared by using thin layer hydration method, and then chitosan solution was added into the Nio-UA to prepare Nio-CS-UA.

Findings/Results: The results showed that increasing the UA amount increased the particle size of Nio-UA. However, the higher the UA amount added to niosomes, the lower the encapsulation efficiency. The highest physical stability was achieved by preparing niosomes at a molar ratio of 3:2:10 for Span® 60, cholesterol, and UA, respectively, with a zeta-potential value of -41.99 mV. The addition of chitosan increased the particle size from 255 nm to 439 nm, as well as the zeta-potential value which increased from -46 mV to -21 mV. Moreover, Nio-UA-CS had relatively higher drug release in PBS pH 6.8 and 7.4 than Nio-UA. In the in vivo study, the addition of chitosan produced higher intensities of coumarin-6-labeled Nio-UA-CS in the liver than Nio-UA.

Conclusion and implications: It can be concluded that the ratio of Span® 60-cholesterol-UA highly affected niosomes physical properties. Moreover, the addition of chitosan improved the stability and drug release as well as oral biodistribution of Nio-UA.

 

 


Keywords


Keywords: Biodistribution; Cancer; Chitosan: Coumarin-6; Niosomes; Ursolic acid.

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References


Wozniak L, Skapska S, Marszałek K. Ursolic acid-a pentacyclic triterpenoid with a wide spectrum of pharmacological activities ursolic acid-a pentacyclic triterpenoid with a wide spectrum of pharmacological activities. Molecules. 2015;20(11):20614-20641.

DOI: 10.3390/molecules201119721.

Seo DY, Lee SR, Heo J, No M, Rhee BD, Ko KS, et al. Ursolic acid in health and disease. Korean J Physiol Pharmacol. 2018;22(3):235-248.

DOI: 10.4196/kjpp.2018.22.3.235.

Hyu MH, Kao TC, Yen GC. Oleanolic acid and ursolic acid induce apoptosis in HuH7 human hepatocellular carcinoma cells through a mitochondrial-dependent pathway and downregulation of XIAP. J Agric Food Chem. 2010;58(10):6110-6118.

DOI: 10.1021/jf100574j.

Gharibi S, Bakhtiari N, Moslemee-Jalalvand E, Bakhtiari F. Ursolic acid mediates hepatic protection through enhancing of anti-aging biomarkers. Curr Aging Sci. 2018;11(1):16-23.

DOI: 10.2174/1874609810666170531103140.

Ma JQ, Ding J, Zhang L, Liu C. Protective effects of ursolic acid in an experimental model of liver fibrosis through Nrf2/ARE pathway. Clin Res Hepatol Gastroenterol. 2015;39(2):188-197.

DOI: 10.1016/j.clinre.2014.09.007.

Geerlofs L, He Z, Xiao S, Xiao ZC. Repeated dose (90 days) oral toxicity study of ursolic acid in Han-Wistar rats. Toxicol Rep. 2020;7:610-623.

DOI: 10.1016/j.toxrep.2020.04.005.

Kim G, Kan S, Kang H, Lee S, Ko HM, Kim JH, et al. Ursolic acid suppresses cholesterol biosynthesis and exerts anti-cancer effects in hepatocellular carcinoma cells. Int J Mol Sci. 2019;20(19):4767,1-15.

DOI: 10.3390/ijms20194767.

Li Y, Xing D, Chen Q, Chen WR. Enhancement of chemotheraputic agent-induced apoptosis by inhibition of NF-kB using ursolic acid. Int J Cancer. 2010;127(2):462-673.

DOI: 10.1002/ijc.25044.

Qian Z, Wang X, Song Z, Zhang H, Zhou S, Zhao J, et al. A phase I trial to evaluate the multiple-dose safety and antitumor activity of ursolic acid liposomes in subjects with advanced solid tumors. Biomed Res Int. 2015;2015:809714,1-7.

DOI: 10.1155/2015/809714.

Eloy JO, Saraiva J, de Albuquerque S, Marchetti JM. Preparation, characterization and evaluation of the in vivo trypanocidal activity of ursolic acid-loaded solid dispersion with poloxamer 407 and sodium caprate. Braz J Pharm Sci. 2015;51(1):101-109.

DOI: 10.1590/S1984-82502015000100011.

Shatalebi MA, Mostafavi SA, Moghaddas A. Niosome as a drug carrier for topical delivery of N-acetyl glucosamine. Res Pharm Sci. 2010;5(2):107-117.

PMID: 21589799.

Hajizadeh MR, Maleki H, Barani M. In vitro cytotoxicity assay of D-limonene niosomes : an efficient nano-carrier for enhancing solubility of plant-extracted agents. Res Pharm Sci. 2019;14(5):448-458.

DOI: 10.4103/1735-5362.268206.

Mirzaei M, Dadashzadeh S, Monavari H, Ebrahimi S. Preparation and characterization of acyclovir loaded nano-niosomes as a potential antiviral drug delivery system. Res Pharm Sci. 2012;7(5):S232.

Abdelaziz AA, Elbanna TE, Sonbol FI, Gamaleldin NM, Maghraby GM El. Optimization of niosomes for enhanced antibacterial activity and reduced bacterial resistance: in vitro and in vivo evaluation. Expert Opin Drug Deliv. 2015;12(2):1-18.

DOI: 10.1517/17425247.2014.942639.

Bhattacharya B, Mondal A, Soni SR, Das S, Bhunia S, Bal Raju K, et al. Multidrug salt forms of norfloxacin with non-steroidal anti-inflammatory drugs: solubility and membrane permeability studies. CrystEngComm. 2018;20(41):6420-6429.

DOI: 10.1039/C8CE00900G.

Sezgin-Bayindir Z, Beşikci A, Yüksel N. Paclitaxel-loaded niosomes for intravenous administration: pharmacokinetics and tissue distribution in rats. Turk J Med Sci. 2015;45(6):1403-1412.

PMID: 26775401.

Wang M, Zhao T, Liu Y, Wang Q, Xing S, Li L, et al. Ursolic acid liposomes with chitosan modification: promising antitumor drug delivery and efficacy. Mater Sci Eng C Mater Biol Appl. 2017;71:1231-1240.

DOI: 10.1016/j.msec.2016.11.014.

Szymańska E, Winnicka K. Stability of chitosan-a challenge for pharmaceutical and biomedical applications. Mar Drugs. 2015;13(4):1819-1846.

DOI: 10.3390/md13041819.

Moghassemi S, Hadjizadeh A. Nano-niosomes as nanoscale drug delivery systems: an illustrated review. J Control Release. 2014;185:22-36.

DOI: 10.1016/j.jconrel.2014.04.015.

Wang M, Liu M, Xie T, Zhang B, Gao X. Chitosan-modified cholesterol-free liposomes for improving the oral bioavailability of progesterone. Colloids Surfaces B Biointerfaces. 2017;159:580-585.

DOI: 10.1016/j.colsurfb.2017.08.028.

Miatmoko A, Salim RH, Zahro SM, Annuryanti F, Sari R, Hendradi E. Dual loading of primaquine and chloroquine into liposome. Eur Pharm J. 2019;66(2):18-25.

DOI: 10.2478/afpuc-2019-0009.

Junyaprasert VB, Teeranachaideekul V, Supaperm T. Effect of charged and non-ionic membrane additives on physicochemical properties and stability of niosomes. AAPS PharmSciTech. 2008;9(3):851-859.

DOI: 10.1208/s12249-008-9121-1.

Aronson H. Correction factor for dissolution profile calculations. J Pharm Sci. 1993;82(11):1190-1190.

DOI: 10.1002/jps.2600821126.

Mohsen AM, AbouSamra MM, ElShebiney SA. Enhanced oral bioavailability and sustained delivery of glimepiride via niosomal encapsulation: in-vitro characterization and in-vivo evaluation. Drug Dev Ind Pharm. 2017;43(8):1254-1264.

DOI: 10.1080/03639045.2017.1310224.

Essa EA. Effect of formulation and processing variables on the particle size of sorbitan monopalmitate niosomes. Asian J Pharm. 2010;4(4):227-233.

DOI: 10.4103/0973-8398.76752.

Fathalla D, Abdel-Mageed A, Abdel-Hamed F, Ahmed M. In-vitro and in-vivo evaluation of niosomal gel containing aceclofenac for sustained drug delivery. Int J Pharm Sci Res. 2014;1:105-115.

DOI: 10.15344/2394-1502/2014/105.

Kharia AA, Singhai AK, Verma R. Formulation and evaluation of polymeric nanoparticles of an antiviral drug for gastroretention. Int J Pharm Sci Nanotech. 2012;4(4):1557-1562.

DOI: 10.37285/ijpsn.2011.4.4.6.

Khan MI, Madni A, Ahmad S, Mahmood MA, Rehman M, Ashfaq M. Formulation design and characterization of a non-ionic surfactant based vesicular system for the sustained delivery of a new chondroprotective agent. Braz J Pharm Sci. 2015;51(3):607-615.

DOI: 10.1590/S1984-82502015000300012.

Abdelkader H, Alani AWG, Alany RG. Recent advances in non-ionic surfactant vesicles (niosomes): self-assembly, fabrication, characterization, drug delivery applications and limitations. Drug Deliv. 2014;21(2):87-100.

DOI: 10.3109/10717544.2013.838077.

Hasan M, Ben Messaoud G, Michaux F, Tamayol A, Kahn C, Belhaj N, et al. Chitosan-coated liposomes encapsulating curcumin: study of lipid-polysaccharide interactions and nanovesicle behavior. RSC Adv. 2016;6(51):45290-45304.

DOI: 10.1039/C6RA05574E.

Rinaldi F, Hanieh PN, King L, Chan N, Angeloni L, Passeri D, et al. Chitosan glutamate-coated niosomes: a proposal for nose-to-brain delivery. Pharmaceutics. 2018;10(2):38-53.

DOI: 10.3390/pharmaceutics10020038.

Li M, Al-Jamal KT, Kostarelos K, Reineke J. Physiologically based pharmacokinetic modeling of nanoparticles. ACS Nano. 2010;4(11):6303-6317.

DOI: 10.1021/nn1018818.

Ge X, Wei M, He S, Yuan W. Advances of non-ionic surfactant vesicles (niosomes) and their application in drug delivery. Pharmaceutics. 2019;11(2):55-70.

DOI: 10.3390/pharmaceutics11020055.

Yu B, Hsu S, Zhou C, Wang X, Terp MC, Wu Y, et al. Lipid nanoparticles for hepatic delivery of small interfering RNA. Biomaterials. 2012;33(25):5924-5934.

DOI: 10.1016/j.biomaterials.2012.05.002.


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