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Current Pharmaceutical Biotechnology

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ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

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Research Article

Preparation of Chitosan/Alginate-ellagic Acid Sustained-release Microspheres and their Inhibition of Preadipocyte Adipogenic Differentiation

Author(s): Chengshi Ding, Haidan Bi, Deya Wang, Meiling Kang, Zhongjing Tian, Yingxia Zhang, Hongkai Wang, Tianshun Zhu* and Jing Ma*

Volume 20, Issue 14, 2019

Page: [1213 - 1222] Pages: 10

DOI: 10.2174/1389201020666190809110511

open access plus

Abstract

Objective: In this study, chitosan/alginate-ellagic acid sustained-release microspheres were prepared, and the effect of sustained-release microspheres on preadipocyte adipogenic differentiation was analyzed.

Methods: Chitosan/alginate-ellagic acid microspheres were prepared and identified by scanning electron microscopy (SEM) and infrared spectroscopy (IR). The drug release rates were measured at pH 6.8, 7.0, 7.2, 7.4 to determine sustained release of ellagic acid from microspheres. The effects of 0.1, 1, 10 mg/L chitosan/alginate-ellagic acid microsphere on 3T3-F442A preadipocyte proliferation were determined by Methyl thiazolyl tetrazolium assay (MTT), and cell morphology was checked by hematoxylin/ eosin staining (HE staining). The effect of chitosan/alginate-ellagic acid microspheres on preadipocyte adipogenic differentiation was also determined by Oil red O staining, and lipogenesis was measured by isopropanol extraction. The molecular mechanism was investigated by detecting the mRNA expression of CCAAT/enhancer binding protein alpha (C/EBPα) and peroxisome proliferatorsactivated receptor gamma (PPARγ).

Results: Chitosan/alginate-ellagic acid sustained-release microspheres were successfully prepared, and the inhibition of proliferation and adipogenic differentiation of preadipocytes was found to be dosedependent. The mechanism of differentiation inhibition was found to be closely related to the expression of transcription factor C/EBPα and PPARγ.

Conclusion: Chitosan/alginate can be used as a good material to prepare ellagic acid sustained-release microspheres, and these microspheres can be used for treating the obesity.

Keywords: Chitosan/alginate, ellagic acid sustained-release microspheres, preparation, adipogenic differentiation, Methyl thiazolyl tetrazolium assay (MTT), preadipocyte.

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[1]
Khan, I.; Rahman, H.; Abd El-Salam, N.M.; Tawab, A.; Hussain, A.; Khan, T.A.; Khan, U.A.; Qasim, M.; Adnan, M.; Azizullah, A.; Murad, W.; Jalal, A.; Muhammad, N.; Ullah, R. Punica granatum peel extracts: HPLC fractionation and LC MS analysis to quest compounds having activity against multidrug resistant bacteria. BMC Complement. Altern. Med., 2017, 17(1), 247.
[http://dx.doi.org/10.1186/s12906-017-1766-4] [PMID: 28468660]
[2]
Wu, S.; Tian, L. Diverse phytochemicals and bioactivities in the ancient fruit and modern functional food pomegranate (Punica granatum). Molecules, 2017, 22(10), 1606.
[http://dx.doi.org/10.3390/molecules22101606] [PMID: 28946708]
[3]
Dell’Agli, M.; Galli, G.V.; Corbett, Y.; Taramelli, D.; Lucantoni, L.; Habluetzel, A.; Maschi, O.; Caruso, D.; Giavarini, F.; Romeo, S.; Bhattacharya, D.; Bosisio, E. Antiplasmodial activity of Punica granatum L. fruit rind. J. Ethnopharmacol., 2009, 125(2), 279-285.
[http://dx.doi.org/10.1016/j.jep.2009.06.025] [PMID: 19577622]
[4]
Priyadarsini, K.I.; Khopde, S.M.; Kumar, S.S.; Mohan, H. Free radical studies of ellagic acid, a natural phenolic antioxidant. J. Agric. Food Chem., 2002, 50(7), 2200-2206.
[http://dx.doi.org/10.1021/jf011275g] [PMID: 11902978]
[5]
Zhang, H.M.; Zhao, L.; Li, H.; Xu, H.; Chen, W.W.; Tao, L. Research progress on the anticarcinogenic actions and mechanisms of ellagic acid. Cancer Biol. Med., 2014, 11(2), 92-100.
[PMID: 25009751]
[6]
Dubey, A.; Park, D.W.; Kwon, J.E.; Jeong, Y.J.; Kim, T.; Kim, I.; Kang, S.C.; Chi, K.W. Investigation of the biological and anti-cancer properties of ellagic acid-encapsulated nano-sized metalla-cages. Int. J. Nanomedicine, 2015, 10(Spec Issue), 227-240.
[PMID: 26366074]
[7]
Wang, L.F. The effect and mechanism of ellagic acid on adipogenesis in 3T3-L1 preadipocytes; Urumqi: Xinjiang Medical University, 2012, pp. 39-58.
[8]
Wang, L.F.; Meng, K.; Li, L.L. The effect and mechanism of ellagic acid on proliferation and differentiation in 3T3-L1 preadipocytes[ J] Chin. J. Hypertens., 2014, 9, 852-854.
[9]
Bell, C.; Hawthorne, S. Ellagic acid, pomegranate and prostate cancer - a mini review. J. Pharm. Pharmacol., 2008, 60(2), 139-144.
[http://dx.doi.org/10.1211/jpp.60.2.0001] [PMID: 18237460]
[10]
Smart, R.C.; Huang, M.T.; Chang, R.L.; Sayer, J.M.; Jerina, D.M.; Conney, A.H. Disposition of the naturally occurring antimutagenic plant phenol, ellagic acid, and its synthetic derivatives, 3-O-decylellagic acid and 3,3′-di-O-methylellagic acid in mice. Carcinogenesis, 1986, 7(10), 1663-1667.
[http://dx.doi.org/10.1093/carcin/7.10.1663] [PMID: 3093111]
[11]
Teel, R.W.; Martin, R.M. Disposition of the plant phenol ellagic acid in the mouse following oral administration by gavage. Xenobiotica, 1988, 18(4), 397-405.
[http://dx.doi.org/10.3109/00498258809041676] [PMID: 3400268]
[12]
Motwani, S.K.; Chopra, S.; Talegaonkar, S.; Kohli, K.; Ahmad, F.J.; Khar, R.K. Chitosan-sodium alginate nanoparticles as submicroscopic reservoirs for ocular delivery: Formulation, optimisation and in vitro characterisation. Eur. J. Pharm. Biopharm., 2008, 68(3), 513-525.
[PMID: 17983737]
[13]
Silva, D.; Sousa, H.C.; Gil, M.H.; Santos, L.F.; Moutinho, G.M.; Serro, A.P.; Saramago, B. Antibacterial layer-by-layer coatings to control drug release from soft contact lenses material. Int. J. Pharm., 2018, 553(1-2), 186-200.
[http://dx.doi.org/10.1016/j.ijpharm.2018.10.041] [PMID: 30342082]
[14]
Mukhopadhyay, P.; Chakraborty, S.; Bhattacharya, S.; Mishra, R.; Kundu, P.P. pH-sensitive chitosan/alginate core-shell nanoparticles for efficient and safe oral insulin delivery. Int. J. Biol. Macromol., 2015, 72(1), 640-648.
[http://dx.doi.org/10.1016/j.ijbiomac.2014.08.040] [PMID: 25239194]
[15]
Kafshgari, M.H.; Khorram, M.; Mansouri, M. Preparation of alginate and chitosan nanoparticles using a new reverse micellar system. Iran. Polym. J., 2012, 21(2), 99-107.
[http://dx.doi.org/10.1007/s13726-011-0010-1]
[16]
Wang, H.; Gong, X.; Guo, X. Characterization, release, and antioxidant activity of curcumin-loaded sodium alginate/ZnO hydrogel beads. Int. J. Biol. Macromol., 2019, 121, 1118-1125.
[http://dx.doi.org/10.1016/j.ijbiomac.2018.10.121] [PMID: 30340010]
[17]
Zhang, X.Z.; Tian, F.J.; Hou, Y.M. Preparation and in vitro-in vivo characterization of polyelectrolyte alginate-chitosan complex based microspheres loaded with verapamil hydrochloride for improved oral drug delivery. J. Incl. Phenom. Macrocycl. Chem., 2015, 81(3), 429-440.
[http://dx.doi.org/10.1007/s10847-014-0471-x]
[18]
Behera, T.; Swain, P. Antigen encapsulated alginate-coated chitosan microspheres stimulate both innate and adaptive immune responses in fish through oral immunization. Aquacult. Int., 2014, 22(2), 673-688.
[http://dx.doi.org/10.1007/s10499-013-9696-8]
[19]
Sui, H.X.; Lv, P.J.; Wang, Y.; Feng, Y.C. Effects of low level laser irradiation on the osteogenic capacity of sodium alginate/gelatin/human adipose-derived stem cells 3D bio-printing construct. Beijing Da Xue Xue Bao, 2018, 50(5), 868-875.
[PMID: 30337750]
[20]
Hussein, M.Z.; Al Ali, S.H.; Zainal, Z.; Hakim, M.N. Development of antiproliferative nanohybrid compound with controlled release property using ellagic acid as the active agent. Int. J. Nanomedicine, 2011, 6, 1373-1383.
[http://dx.doi.org/10.2147/IJN.S21567] [PMID: 21796241]
[21]
Mady, F.M.; Ibrahim, S.R. Cyclodextrin-based nanosponge for improvement of solubility and oral bioavailability of Ellagic acid. Pak. J. Pharm. Sci., 2018, 31((5 Suppl.)), 2069-2076.
[PMID: 30393214]
[22]
Wang, H.; Zhang, Y.; Tian, Z.; Ma, J.; Kang, M.; Ding, C.; Ming, D. Preparation of β-CD-ellagic acid microspheres and their effects on HepG2 cell proliferation. Molecules, 2017, 22(12), 2175.
[http://dx.doi.org/10.3390/molecules22122175] [PMID: 29292740]
[23]
Zhang, H.; Jin, S.Y.; Zhou, H.M.; Chen, W.; Zhu, S.F. Preparation and in vitro release of ellagic acid microspheres. Zhongguo Shiyan Fangjixue Zazhi, 2015, 21(7), 11-13.
[24]
Li, S.; Li, X.R.; Hou, X.P. Preparation and drug-loading capacity of alginate-chitosan microcapsules. J. Chin. Clin. Med., 2002, 3(14), 1-3.
[25]
Sharma, G.; Italia, J.L.; Sonaje, K.; Tikoo, K.; Ravi Kumar, M.N. Biodegradable in situ gelling system for subcutaneous administration of ellagic acid and ellagic acid loaded nanoparticles: Evaluation of their antioxidant potential against cyclosporine induced nephrotoxicity in rats. J. Control. Release, 2007, 118(1), 27-37.
[http://dx.doi.org/10.1016/j.jconrel.2006.11.026] [PMID: 17258836]
[26]
Gan, X.; Chen, Y.N.; Yu, L.; Zhu, K.C.; Zeng, X.Y.; Bai, Q. Optimization of extraction technology of ellagic acid from pomegranate peels with orthogonal experiment. Agric. Sci. Technol., 2012, 13, 2404-2408.
[27]
Bansal, S.S.; Goel, M.; Aqil, F.; Vadhanam, M.V.; Gupta, R.C. Advanced drug delivery systems of curcumin for cancer chemoprevention. Cancer Prev. Res. (Phila.), 2011, 4(8), 1158-1171.
[http://dx.doi.org/10.1158/1940-6207.CAPR-10-0006] [PMID: 21546540]
[28]
Bala, I.; Bhardwaj, V.; Hariharan, S.; Kharade, S.V.; Roy, N.; Ravi Kumar, M.N. Sustained release nanoparticulate formulation containing antioxidant-ellagic acid as potential prophylaxis system for oral administration. J. Drug Target., 2006, 14(1), 27-34.
[http://dx.doi.org/10.1080/10611860600565987] [PMID: 16603449]
[29]
Liu, C.; Huang, K.; Li, G.; Wang, P.; Liu, C.; Guo, C.; Sun, Z.; Pan, J. Ascorbic acid promotes 3T3-L1 cells adipogenesis by attenuating ERK signaling to upregulate the collagen VI. Nutr. Metab. (Lond.), 2017, 14, 79.
[http://dx.doi.org/10.1186/s12986-017-0234-y] [PMID: 29299041]
[30]
Gong, M.; Liu, C.; Zhang, L.; Zhang, H.; Pan, J. Loss of the TNFα function inhibits Wnt/β-catenin signaling, exacerbates obesity development in adolescent spontaneous obese mice. Mol. Cell. Biochem., 2014, 391(1-2), 59-66.
[http://dx.doi.org/10.1007/s11010-014-1987-5] [PMID: 24522555]
[31]
Xiong, Y.; Xu, Q.; Lin, S. Knockdown of LXRα inhibits goat intramuscular preadipocyte differentiation. Int. J. Mol. Sci., 2018, 19(10), 3037.
[http://dx.doi.org/10.3390/ijms19103037]
[32]
Fan, Z. Explore the interaction mechanism between TNF-α and β-catenin signal pathway in the primary preadipose differentiation of mice; Jinan, Shandong Normal University, 2013, pp. 32-39. [D]
[33]
Zhang, H.; Zhao, S.; Zhang, L.; Han, B.; Yao, X.; Chen, W.; Hu, Y. Preparation of ellagic acid molecularly imprinted polymeric microspheres based on distillation-precipitation polymerization for the efficient purification of a crude extract. J. Sep. Sci., 2016, 39(16), 3098-3104.
[http://dx.doi.org/10.1002/jssc.201600355] [PMID: 27311588]
[34]
Wu, D.; Ma, X.F.; Tian, W.X. Pomegranate husk extract, punicalagin and ellagic acid inhibit fatty acid synthase and adipogenesis of 3T3-L1 adipocyte. J. Funct. Foods, 2013, 5(2), 633-641.
[http://dx.doi.org/10.1016/j.jff.2013.01.005]
[35]
Cheng, N.; Wang, Y.; Cao, W. The protective effect of whole honey and phenolic extract on oxidative DNA damage in mice lymphocytes using comet assay. Plant Foods Hum. Nutr., 2017, 72(4), 388-395.
[http://dx.doi.org/10.1007/s11130-017-0634-1] [PMID: 28929426]
[36]
Hosseini, A.; Bakhtiari, E.; Mousavi, S.H. Protective effect of Hibiscus sabdariffa on doxorubicin-induced cytotoxicity in H9c2 cardiomyoblast cells. Iran. J. Pharm. Res., 2017, 16(2), 708-713.
[PMID: 28979325]
[37]
Ma, X.; Wei, D.; Cheng, G.; Li, S.; Wang, L.; Wang, Y.; Wang, X.; Zhang, S.; Wang, H.; Zan, L. Bta-miR-130a/b regulates preadipocyte differentiation by targeting PPARG and CYP2U1 in beef cattle. Mol. Cell. Probes, 2018, 42, 10-17.
[http://dx.doi.org/10.1016/j.mcp.2018.10.002] [PMID: 30336279]
[38]
Shen, G.S.; Zhou, H.B.; Zhang, H.; Chen, B.; Liu, Z.P.; Yuan, Y.; Zhou, X.Z.; Xu, Y.J. The GDF11-FTO-PPARγ axis controls the shift of osteoporotic MSC fate to adipocyte and inhibits bone formation during osteoporosis. Biochim. Biophys. Acta Mol. Basis Dis., 2018, 1864(12), 3644-3654.
[http://dx.doi.org/10.1016/j.bbadis.2018.09.015] [PMID: 30279140]
[39]
Li, H.X.; Wang, C.F.; Zhang, H.L. Study on extract technology of ellagic acid in the peels of Punica granatum. China Med. Herald., 2008, 5(24), 50-52.

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