Nano-soldiers Ameliorate Silibinin Delivery: A Review Study

Author(s): Milad Ashrafizadeh, Zahra Ahmadi, Reza Mohammadinejad, Tahereh Farkhondeh, Saeed Samarghandian*

Journal Name: Current Drug Delivery

Volume 17 , Issue 1 , 2020

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Flavonoids are a large group of naturally occurring compounds, which are of interest due to their great pharmacological effects and health-promoting impacts. These properties have led to their extensive application in a variety of pathological conditions, particularly cancer. Flavonoids are used in large quantities in a human's daily diet and a high amount of flavonoids are found in the intestine after oral usage. However, flavonoid concentrations in tissue/plasma are low because of their low bioavailability, the leading to the low efficacy of flavonoids in different clinical disorders. For this reason, nanotechnology application for delivering flavonoids to tumor sites has recently received significant attention. Silibinin is a key member of flavonoids and a bioactive component of silymarin, which is widely isolated from Silybum marianum. This plant-derived chemical has a number of valuable biological and therapeutic activities such as antioxidant, anti-inflammatory, neuroprotective, anti-tumor, hepatoprotective, cardioprotective and anti-diabetic. These beneficial effects have been demonstrated in in vivo and in vitro experiments. However, it seems that silibinin has a variety of limitations and poor bioavailability is the most important factor restricting its wide application. Hence, there have been attempts to improve the bioavailability of silibinin and it has been suggested that nano-soldiers are potential candidates for this aim. In the present review, we describe the different drug delivery systems for improving the bioavailability of silibinin.

Keywords: Silibinin, Drug delivery, Bioavailability, Herbal medicine, Cancer therapy, Pharmacological effects.

Imran, M.; Rauf, A.; Abu-Izneid, T.; Nadeem, M.; Shariati, M.A.; Khan, I.A.; Imran, A.; Orhan, I.E.; Rizwan, M.; Atif, M.; Gondal, T.A.; Mubarak, M.S. Luteolin, a flavonoid, as an anticancer agent: A review. Biomed. Pharmacother., 2019, 112108612
[] [PMID: 30798142]
Samarghandian, S.; Azimi-Nezhad, M.; Farkhondeh, T. Thymoquinone-induced antitumor and apoptosis in human lung adenocarcinoma cells. J. Cell. Physiol., 2019, 234(7), 10421-10431.
[] [PMID: 30387147]
Ashrafizadeh, M.; Mohammadinejad, R.; Tavakol, S.; Ahmadi, Z.; Roomiani, S.; Katebi, M. Autophagy, anoikis, ferroptosis, necroptosis, and endoplasmic reticulum stress: Potential applications in melanoma therapy. J. Cell. Physiol., 2019, 234(11), 19471-19479.
[] [PMID: 31032940]
Mohammadinejad, R.; Ahmadi, Z.; Tavakol, S.; Ashrafizadeh, M. Berberine as a potential autophagy modulator. J. Cell. Physiol., 2019.
[] [PMID: 30770555]
Sobhani, B. Histopathological analysis of testis: Effects of astaxanthin treatment against nicotine toxicity. Iranian J. Toxicol., 2019, 13(1), 41-44.
Ahmadi, Z.; Mohammadinejad, R.; Ashrafizadeh, M. Drug delivery systems for resveratrol, a non-flavonoid polyphenol: Emerging evidence in last decades. J. Drug Deliv. Sci. Technol., 2019, 51, 591-604.
Ashrafizadeh, M.; Ahmadi, Z. The effects of astaxanthin treatment on the sperm quality of mice treated with nicotine. Rev. Clin. Med., 2019, 6(1), 156-158.
Farkhondeh, T.; Samarghandian, S.; Roshanravan, B. Impact of chrysin on the molecular mechanisms underlying diabetic complications. J. Cell. Physiol., 2019, 234(10), 17144-17158.
[] [PMID: 30916403]
Farkhondeh, T.; Samarghandian, S.; Pourbagher-Shahri, A.M.; Sedaghat, M. The impact of curcumin and its modified formulations on Alzheimer’s disease. J. Cell. Physiol., 2019, 234(10), 16953-16965.
[] [PMID: 30847942]
Farkhondeh, T.; Samarghandian, S.; Pourbagher-Shahri, A.M. Hypolipidemic effects of Rosmarinus officinalis L. J. Cell. Physiol., 2019.
[] [PMID: 30693502]
Imran, M.; Rauf, A.; Shah, Z.A.; Saeed, F.; Imran, A.; Arshad, M.U.; Ahmad, B.; Bawazeer, S.; Atif, M.; Peters, D.G.; Mubarak, M.S. Chemo-preventive and therapeutic effect of the dietary flavonoid kaempferol: A comprehensive review. Phytother. Res., 2019, 33(2), 263-275.
[] [PMID: 30402931]
Wang, L.; Lee, I.M.; Zhang, S.M.; Blumberg, J.B.; Buring, J.E.; Sesso, H.D. Dietary intake of selected flavonols, flavones, and flavonoid-rich foods and risk of cancer in middle-aged and older women. Am. J. Clin. Nutr., 2009, 89(3), 905-912.
[] [PMID: 19158208]
Cui, S.; Tang, J.; Wang, S.; Li, L. Kaempferol protects lipopolysaccharide-induced inflammatory injury in human aortic endothelial cells (HAECs) by regulation of miR-203. Biomed. Pharmacother., 2019, 115108888
[] [PMID: 31022599]
Zhang, N. Protective effects of Kaempferol on D-Ribose-Induced Mesangial cell injury. Oxid. Med. Cell. Longev., 2019, 20197564207
[] [PMID: 31049137]
Zhang, F.; Ma, C. Kaempferol suppresses human gastric cancer SNU-216 cell proliferation, promotes cell autophagy, but has no influence on cell apoptosis. Braz. J. Med. Biol. Res., 2019, 52(2)e7843
[] [PMID: 30785478]
Moradzadeh, M.; Tabarraei, A.; Sadeghnia, H.R.; Ghorbani, A.; Mohamadkhani, A.; Erfanian, S.; Sahebkar, A. Kaempferol increases apoptosis in human acute promyelocytic leukemia cells and inhibits multidrug resistance genes. J. Cell. Biochem., 2018, 119(2), 2288-2297.
[] [PMID: 28865123]
Navolokin, N.A. Effect of extracts of Gratiola officinalis and Zea mays on the tumor and the morphology of the internal organs of rats with transplanted liver cancer. Russ. Open Med. J., 2012, 1(4), 0203.
Polukonova, The apoptotic activity of flavonoid-containing Gratiola officinalis extract in cell cultures of human kidney cancer. Russ. Open Med. J., 2018, 7(4), 402.
Mateen, S.; Raina, K.; Agarwal, R. Chemopreventive and anti-cancer efficacy of silibinin against growth and progression of lung cancer. Nutrition and cancer, 2013, 65, 3-11.
Raina, K.; Kumar, S.; Dhar, D.; Agarwal, R. Silibinin and colorectal cancer chemoprevention: A comprehensive review on mechanisms and efficacy. J. Biomed. Res., 2016, 30(6), 452-465.
[PMID: 27476880]
Tewari-Singh, N.; Agarwal, R. Mustard vesicating agent-induced toxicity in the skin tissue and silibinin as a potential countermeasure. Ann. N. Y. Acad. Sci., 2016, 1374(1), 184-192.
[] [PMID: 27326543]
Wu, J-W.; Lin, L.C.; Hung, S.C.; Lin, C.H.; Chi, C.W.; Tsai, T.H. Hepatobiliary excretion of silibinin in normal and liver cirrhotic rats. Drug Metab. Dispos., 2008, 36(3), 589-596.
[] [PMID: 18048488]
Bai, D.; Jin, G.; Zhang, D.; Zhao, L.; Wang, M.; Zhu, Q.; Zhu, L.; Sun, Y.; Liu, X.; Chen, X.; Zhang, L.; Li, W.; Cui, Y. Natural silibinin modulates amyloid precursor protein processing and amyloid-β protein clearance in APP/PS1 mice. J. Physiol. Sci., 2019, 69(4), 643-652.
[] [PMID: 31087219]
Matias, M.L.; Gomes, V.J.; Romao-Veiga, M.; Ribeiro, V.R.; Nunes, P.R.; Romagnoli, G.G.; Peracoli, J.C.; Peracoli, M.T.S. Silibinin downregulates the NF-κB pathway and NLRP1/NLRP3 inflammasomes in monocytes from pregnant women with preeclampsia. Molecules, 2019, 24(8), 1548.
[] [PMID: 31010153]
Rigby, C.; Deep, G.; Jain, A.; Orlicky, D.J.; Agarwal, C.; Agarwal, R. Silibinin inhibits ultraviolet B radiation-induced mast cells recruitment and bone morphogenetic protein 2 expression in the skin at early stages in Ptch(+/-) mouse model of basal cell carcinoma. Mol. Carcinog., 2019, 58(7), 1260-1271.
[] [PMID: 30912211]
Muthumani, M.; Prabu, S.M. Silibinin potentially attenuates arsenic-induced oxidative stress mediated cardiotoxicity and dyslipidemia in rats. Cardiovasc. Toxicol., 2014, 14(1), 83-97.
[] [PMID: 24062023]
Li, Y.; Ren, L.; Song, G.; Zhang, P.; Yang, L.; Chen, X.; Yu, X.; Chen, S. Silibinin ameliorates fructose-induced lipid accumulation and activates autophagy in HepG2 Cells. Endocr. Metab. Immune Disord. Drug Targets, 2019, 19(5), 632-642.
[] [PMID: 30734689]
Liu, B.; Liu, W.; Liu, P.; Liu, X.; Song, X.; Hayashi, T.; Onodera, S.; Ikejima, T. Silibinin alleviates the learning and memory defects in overtrained rats accompanying reduced neuronal apoptosis and senescence. Neurochem. Res., 2019, 44(8), 1818-1829.
[] [PMID: 31102026]
Xu, F.; Yang, J.; Negishi, H.; Sun, Y.; Li, D.; Zhang, X.; Hayashi, T.; Gao, M.; Ikeda, K.; Ikejima, T. Silibinin decreases hepatic glucose production through the activation of gut-brain-liver axis in diabetic rats. Food Funct., 2018, 9(9), 4926-4935.
[] [PMID: 30178798]
Si, L.; Liu, W.; Hayashi, T.; Ji, Y.; Fu, J.; Nie, Y.; Mizuno, K.; Hattori, S.; Onodera, S.; Ikejima, T. Silibinin-induced apoptosis of breast cancer cells involves mitochondrial impairment. Arch. Biochem. Biophys., 2019, 671, 42-51.
[] [PMID: 31085166]
Bai, Z-L. Silibinin induced human glioblastoma cell apoptosis concomitant with autophagy through simultaneous inhibition of mTOR and YAP. BioMed Res. Int., 2018, 2018, 1-10.
German, S.V.; Bratashov, D.N.; Navolokin, N.A.; Kozlova, A.A.; Lomova, M.V.; Novoselova, M.V.; Burilova, E.A.; Zyev, V.V.; Khlebtsov, B.N.; Bucharskaya, A.B.; Terentyuk, G.S.; Amirov, R.R.; Maslyakova, G.N.; Sukhorukov, G.B.; Gorin, D.A. In vitro and in vivo MRI visualization of nanocomposite biodegradable microcapsules with tunable contrast. Phys. Chem. Chem. Phys., 2016, 18(47), 32238-32246.
[] [PMID: 27849068]
Navolokin, N.A.; German, S.V.; Bucharskaya, A.B.; Godage, O.S.; Zuev, V.V.; Maslyakova, G.N.; Pyataev, N.A.; Zamyshliaev, P.S.; Zharkov, M.N.; Terentyuk, G.S.; Gorin, D.A.; Sukhorukov, G.B. Systemic administration of polyelectrolyte microcapsules: Where do they accumulate and when? In vivo and ex vivo study. Nanomaterials (Basel), 2018, 8(10)E812
[] [PMID: 30308931]
Mahmoodi Chalbatani, G.; Dana, H.; Gharagouzloo, E.; Grijalvo, S.; Eritja, R.; Logsdon, C.D.; Memari, F.; Miri, S.R.; Rad, M.R.; Marmari, V. Small interfering RNAs (siRNAs) in cancer therapy: A nano-based approach. Int. J. Nanomedicine, 2019, 14, 3111-3128.
[] [PMID: 31118626]
Rai, R.; Alwani, S.; Badea, I. Polymeric nanoparticles in gene therapy: New avenues of design and optimization for delivery applications. Polymers (Basel), 2019, 11(4), 745.
[] [PMID: 31027272]
Nikam, R.R.; Gore, K.R. Journey of siRNA: Clinical developments and targeted delivery. Nucleic Acid Ther., 2018, 28(4), 209-224.
Zhao, J.; Weng, G.; Li, J.; Zhu, J.; Zhao, J. Polyester-based nanoparticles for nucleic acid delivery. Mater. Sci. Eng. C, 2018, 92, 983-994.
[] [PMID: 30184828]
Rozema, D.B.; Lewis, D.L.; Wakefield, D.H.; Wong, S.C.; Klein, J.J.; Roesch, P.L.; Bertin, S.L.; Reppen, T.W.; Chu, Q.; Blokhin, A.V.; Hagstrom, J.E.; Wolff, J.A. Dynamic poly conjugates for targeted in vivo delivery of siRNA to hepatocytes. Proc. Natl. Acad. Sci. USA, 2007, 104(32), 12982-12987.
[] [PMID: 17652171]
Wagner, E. Polymers for siRNA delivery: Inspired by viruses to be targeted, dynamic, and precise. Acc. Chem. Res., 2012, 45(7), 1005-1013.
[] [PMID: 22191535]
Kuen, C.Y.; Fakurazi, S.; Othman, S.S.; Masarudin, M.J. Increased loading, efficacy and sustained release of silibinin, a poorly soluble drug using hydrophobically-modified chitosan nanoparticles for enhanced delivery of anticancer drug delivery systems. Nanomaterials (Basel), 2017, 7(11), 379.
[] [PMID: 29117121]
Hossainzadeh, S.; Ranji, N.; Naderi Sohi, A.; Najafi, F. Silibinin encapsulation in polymersome: A promising anticancer nanoparticle for inducing apoptosis and decreasing the expression level of miR-125b/miR-182 in human breast cancer cells. J. Cell. Physiol., 2019, 234(12), 22285-22298.
[] [PMID: 31073992]
Leena, R.S.; Vairamani, M.; Selvamurugan, N. Alginate/Gelatin scaffolds incorporated with Silibinin-loaded Chitosan nanoparticles for bone formation in vitro. Colloids Surf. B Biointerfaces, 2017, 158, 308-318.
[] [PMID: 28711017]
Ochi, M.M.; Amoabediny, G.; Rezayat, S.M.; Akbarzadeh, A.; Ebrahimi, B. In vitro co-delivery evaluation of novel pegylated nano-liposomal herbal drugs of silibinin and glycyrrhizic acid (nano-phytosome) to hepatocellular carcinoma cells. Cell J., 2016, 18(2), 135-148.
[PMID: 27540518]
Amirsaadat, S.; Pilehvar-Soltanahmadi, Y.; Zarghami, F.; Alipour, S.; Ebrahimnezhad, Z.; Zarghami, N. Silibinin-loaded magnetic nanoparticles inhibit hTERT gene expression and proliferation of lung cancer cells. Artif. Cells Nanomed. Biotechnol., 2017, 45(8), 1649-1656.
[] [PMID: 28078913]
Shetty, P.K.; Manikkath, J.; Tupally, K.; Kokil, G.; Hegde, A.R.; Raut, S.Y.; Parekh, H.S.; Mutalik, S. Skin delivery of EGCG and silibinin: Potential of peptide dendrimers for enhanced skin permeation and deposition. AAPS PharmSciTech, 2017, 18(6), 2346-2357.
[] [PMID: 28124212]
Makhmalzadeh, B.S.; Molavi, O.; Vakili, M.R.; Zhang, H.F.; Solimani, A.; Abyaneh, H.S.; Loebenberg, R.; Lai, R.; Lavasanifar, A. Functionalized caprolactone-polyethylene glycol based thermo-responsive hydrogels of silibinin for the treatment of malignant melanoma. J. Pharm. Pharm. Sci., 2018, 21(1), 143-159.
[] [PMID: 29789104]
Bangham, A.D.; Standish, M.M.; Watkins, J.C. Diffusion of univalent ions across the lamellae of swollen phospholipids. J. Mol. Biol., 1965, 13(1), 238-252.
[] [PMID: 5859039]
Mukherjee, A.; Waters, A.K.; Kalyan, P.; Achrol, A.S.; Kesari, S.; Yenugonda, V.M. Lipid-polymer hybrid nanoparticles as a next-generation drug delivery platform: State of the art, emerging technologies, and perspectives. Int. J. Nanomedicine, 2019, 14, 1937-1952.
[] [PMID: 30936695]
Moghimi, S.M.; Szebeni, J. Stealth liposomes and long circulating nanoparticles: Critical issues in pharmacokinetics, opsonization and protein-binding properties. Prog. Lipid Res., 2003, 42(6), 463-478.
[] [PMID: 14559067]
Torchilin, V.P. Recent advances with liposomes as pharmaceutical carriers. Nat. Rev. Drug Discov., 2005, 4(2), 145-160.
[] [PMID: 15688077]
Askarizadeh, A.; Butler, A.E.; Badiee, A.; Sahebkar, A. Liposomal nanocarriers for statins: A pharmacokinetic and pharmacodynamics appraisal. J. Cell. Physiol., 2019, 234(2), 1219-1229.
[] [PMID: 30203471]
Mahira, S.; Kommineni, N.; Husain, G.M.; Khan, W. Cabazitaxel and silibinin co-encapsulated cationic liposomes for CD44 targeted delivery: A new insight into nanomedicine based combinational chemotherapy for prostate cancer. Biomed. Pharmacother., 2019, 110, 803-817.
[] [PMID: 30554119]
Shiraishi, K.; Yokoyama, M. Toxicity and immunogenicity concerns related to PEGylated-micelle carrier systems: A review. Sci. Technol. Adv. Mater., 2019, 20(1), 324-336.
[] [PMID: 31068982]
Bader, H.; Ringsdorf, H.; Schmidt, B. Watersoluble polymers in medicine. Angew. Makromolek. Chem., 1984, 123(1), 457-485.
Isoglu, I.A.; Ozsoy, Y.; Isoglu, S.D. Advances in micelle-based drug delivery: Cross-linked systems. Curr. Top. Med. Chem., 2017, 17(13), 1469-1489.
[] [PMID: 28017154]
Dong, X.Y.; Lang, T.Q.; Yin, Q.; Zhang, P.C.; Li, Y.P. Co-delivery of docetaxel and silibinin using pH-sensitive micelles improves therapy of metastatic breast cancer. Acta Pharmacol. Sin., 2017, 38(12), 1655-1662.
[] [PMID: 28713159]
Osanloo, M. Niosome-loaded antifungal drugs as an effective nanocarrier system: A mini review. Cur. Med. Mycol., 2018, 4(4), 31.
Gharbavi, M. Niosome: A promising nanocarrier for natural drug delivery through blood-brain barrier. Adv. Pharmacol. Sci., 2018, 2018
Hakamivala, A.; Moghassemi, S.; Omidfar, K. Modeling and optimization of the niosome nanovesicles using response surface methodology for delivery of insulin. Biomed. Phys. Eng. Express, 2019.
Moghassemi, S.; Hadjizadeh, A. Nano-niosomes as nanoscale drug delivery systems: an illustrated review. J. Control. Release, 2014, 185, 22-36.
[] [PMID: 24747765]
Zeng, W.; Li, Q.; Wan, T.; Liu, C.; Pan, W.; Wu, Z.; Zhang, G.; Pan, J.; Qin, M.; Lin, Y.; Wu, C.; Xu, Y. Hyaluronic acid-coated niosomes facilitate tacrolimus ocular delivery: Mucoadhesion, precorneal retention, aqueous humor pharmacokinetics, and transcorneal permeability. Colloids Surf. B Biointerfaces, 2016, 141, 28-35.
[] [PMID: 26820107]
Behtash, A.; Nafisi, S.; Maibach, H.I. New generation of fluconazole: A review on existing researches and technologies. Curr. Drug Deliv., 2017, 14(1), 2-15.
[] [PMID: 27138299]
Soliman, O.A.E.; Mohamed, E.A.; Khatera, N.A.A. Enhanced ocular bioavailability of fluconazole from niosomal gels and microemulsions: formulation, optimization, and in vitro-in vivo evaluation. Pharm. Dev. Technol., 2019, 24(1), 48-62.
[] [PMID: 29210317]
Haque, F.; Sajid, M.; Cameotra, S.S.; Battacharyya, M.S. Anti-biofilm activity of a sophorolipid-amphotericin B niosomal formulation against Candida albicans. Biofouling, 2017, 33(9), 768-779.
[] [PMID: 28946803]
Yazdi Rouholamini, S.E.; Moghassemi, S.; Maharat, Z.; Hakamivala, A.; Kashanian, S.; Omidfar, K. Effect of silibinin-loaded nano-niosomal coated with trimethyl chitosan on miRNAs expression in 2D and 3D models of T47D breast cancer cell line. Artif. Cells Nanomed. Biotechnol., 2018, 46(3), 524-535.
[] [PMID: 28509572]
Xu, P.; Yin, Q.; Shen, J.; Chen, L.; Yu, H.; Zhang, Z.; Li, Y. Synergistic inhibition of breast cancer metastasis by silibinin-loaded lipid nanoparticles containing TPGS. Int. J. Pharm., 2013, 454(1), 21-30.
[] [PMID: 23830941]
Sun, H.P.; Su, J.H.; Meng, Q.S.; Yin, Q.; Zhang, Z.W.; Yu, H.J.; Zhang, P.C.; Wang, S.L.; Li, Y.P. Silibinin and indocyanine green-loaded nanoparticles inhibit the growth and metastasis of mammalian breast cancer cells in vitro. Acta Pharmacol. Sin., 2016, 37(7), 941-949.
[] [PMID: 27133295]
Mohajeri, M.; Behnam, B.; Barreto, G.E.; Sahebkar, A. Carbon nanomaterials and amyloid-beta interactions: Potentials for the detection and treatment of Alzheimer’s disease? Pharmacol. Res., 2019, 143, 186-203.
[] [PMID: 30943430]
Mohajeri, M.; Behnam, B.; Sahebkar, A. Biomedical applications of carbon nanomaterials: Drug and gene delivery potentials. J. Cell. Physiol., 2018, 234(1), 298-319.
[] [PMID: 30078182]
Rezaee, M.; Behnam, B.; Banach, M.; Sahebkar, A. The Yin and Yang of carbon nanomaterials in atherosclerosis. Biotechnol. Adv., 2018, 36(8), 2232-2247.
[] [PMID: 30342084]
Tan, J.M.; Karthivashan, G.; Gani, S.A.; Fakurazi, S.; Hussein, M.Z. In vitro drug release characteristic and cytotoxic activity of silibinin-loaded single walled carbon nanotubes functionalized with biocompatible polymers. Chem. Cent. J., 2016, 10(1), 81.
[] [PMID: 28028386]
Amiri, B.; Ebrahimi-Far, M.; Saffari, Z.; Akbarzadeh, A.; Soleimani, E.; Chiani, M. Preparation, characterization and cytotoxicity of silibinin-containing nanoniosomes in T47D human breast carcinoma cells. Asian Pac. J. Cancer Prev., 2016, 17(8), 3835-3838.
[PMID: 27644625]
Ripoli, M.; Angelico, R.; Sacco, P.; Ceglie, A.; Mangia, A. Phytoliposome-based silibinin delivery system as a promising strategy to prevent Hepatitis C virus infection. J. Biomed. Nanotechnol., 2016, 12(4), 770-780.
[] [PMID: 27301203]
Pooja, D.; Babu Bikkina, D.J.; Kulhari, H.; Nikhila, N.; Chinde, S.; Raghavendra, Y.M.; Sreedhar, B.; Tiwari, A.K. Fabrication, characterization and bioevaluation of silibinin loaded chitosan nanoparticles. Int. J. Biol. Macromol., 2014, 69, 267-273.
[] [PMID: 24863917]
Gohulkumar, M.; Gurushankar, K.; Prasad, N.R.; Krishnakumar, N. Enhanced cytotoxicity and apoptosis-induced anticancer effect of silibinin-loaded nanoparticles in oral carcinoma (KB) cells. Mater. Sci. Eng. C, 2014, 41, 274-282.
[] [PMID: 24907761]
Nguyen, M-H.; Yu, H.; Dong, B.; Hadinoto, K. A supersaturating delivery system of silibinin exhibiting high payload achieved by amorphous nano-complexation with chitosan. Eur. J. Pharm. Sci., 2016, 89, 163-171.
[] [PMID: 27140843]
Dube, D.; Khatri, K.; Goyal, A.K.; Mishra, N.; Vyas, S.P. Preparation and evaluation of galactosylated vesicular carrier for hepatic targeting of silibinin. Drug Dev. Ind. Pharm., 2010, 36(5), 547-555.
[] [PMID: 19895190]

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2020
Published on: 11 November, 2019
Page: [15 - 22]
Pages: 8
DOI: 10.2174/1567201816666191112113031
Price: $65

Article Metrics

PDF: 27