Silybin-based herbal nanocarriers: an advancement in anticancer therapy

References

• Ali ES, Sharker SM, Islam MT , et al. Targeting cancer cells with nanotherapeutics and nanodiagnostics: current status and future perspectives, Seminars in Cancer Biology. Academic Press : Cambridge, MA, USA. Elsevier; 2020. 52–68 .
   Google Scholar
• Iqbal J, Abbasi BA, Ahmad R, et al. Nanomedicines for developing cancer nanotherapeutics: from benchtop to bedside and beyond. Appl Microbiol Biotechnol. 2018;102(22):9449–9470.
   PubMed Web of Science ®Google Scholar
• Kooti W, Servatyari K, Behzadifar M, et al. Effective medicinal plant in cancer treatment, part 2: review study. J Evid Based Complementary Altern Med. 2017;22(4):982–995.
   PubMedGoogle Scholar
• Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.
   PubMed Web of Science ®Google Scholar
• Khazaei Z, Mosavi Jarrahi A, Momenabadi V, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide stomach cancers and their relationship with the human development index (HDI. World Cancer Res J. 2019;6:e1257.
   Google Scholar
• Rizwanullah M, Amin S, Mir SR, et al. Phytochemical based nanomedicines against cancer: current status and future prospects. J Drug Target. 2018;26(9):731–752.
   PubMed Web of Science ®Google Scholar
• Sun L-R, Zhou W, Zhang H-M, et al. Modulation of multiple signaling pathways of the plant-derived natural products in cancer. Front Oncol. 2019;9:1153.
   PubMed Web of Science ®Google Scholar
• Aljuffali IA, Fang C-L, Chen C-H, et al. Nanomedicine as a strategy for natural compound delivery to prevent and treat cancers. Curr Pharm Des. 2016;22(27):4219–4231.
   PubMedGoogle Scholar
• Davatgaran-Taghipour Y, Masoomzadeh S, Farzaei MH, et al. Polyphenol nanoformulations for cancer therapy: experimental evidence and clinical perspective. Int J Nanomedicine. 2017;12:2689.
   PubMed Web of Science ®Google Scholar
• Mbaveng AT, Kuete V, Efferth T. Potential of central, eastern and western Africa medicinal plants for cancer therapy: spotlight on resistant cells and molecular targets. Front Pharmacol. 2017;8:343.
   PubMedGoogle Scholar
• Bijak M. Silybin, a major bioactive component of milk thistle (Silybum marianum L. Gaernt.)—Chemistry, bioavailability, and metabolism. Molecules. 2017;22(11):1942.
   PubMed Web of Science ®Google Scholar
• Biedermann D, Vavříková E, Cvak L, et al. Chemistry of silybin, Natural product reports. Natural product reports . 2014;31(9):1138–1157.
   PubMed Web of Science ®Google Scholar
• Christodoulou E, Kechagia I-A, Tzimas S, et al. Serum and tissue pharmacokinetics of silibinin after per os and iv administration to mice as a HP-β-CD lyophilized product. Int J Pharm. 2015;493(1–2):366–373.
   PubMedGoogle Scholar
• Fenclova M, Novakova A, Viktorova J, et al. Poor chemical and microbiological quality of the commercial milk thistle-based dietary supplements may account for their reported unsatisfactory and non-reproducible clinical outcomes. Sci Rep. 2019;9(1):1–12.
   PubMedGoogle Scholar
• Chambers CS, Holečková V, Petrásková L, et al. The silymarin composition … and why does it matter??? Food Res Int. 2017;100:339–353.
   PubMed Web of Science ®Google Scholar
• Sagar SM. Future directions for research on Silybum marianum for cancer patients. Integr Cancer Ther. 2007;6(2):166–173.
   PubMedGoogle Scholar
• Abenavoli L, Izzo AA, Milić N, et al. Milk thistle (Silybum marianum): a concise overview on its chemistry, pharmacological, and nutraceutical uses in liver diseases. Phytother Res. 2018;32(11):2202–2213.
   PubMed Web of Science ®Google Scholar
• Tajmohammadi A, Razavi BM, Hosseinzadeh H. Silybum marianum (milk thistle) and its main constituent, silymarin, as a potential therapeutic plant in metabolic syndrome: a review. Phytother Res. 2018;32(10):1933–1949.
   PubMed Web of Science ®Google Scholar
• Vaid M, Katiyar SK. Molecular mechanisms of inhibition of photocarcinogenesis by silymarin, a phytochemical from milk thistle (Silybum marianum L. Gaertn. Int J Oncol. 2010;36(5):1053–1060.
   PubMedGoogle Scholar
• Wu T, Liu W, Guo W, et al. Silymarin suppressed lung cancer growth in mice via inhibiting myeloid-derived suppressor cells. Biomed Pharmacother. 2016;81:460–467.
   PubMedGoogle Scholar
• Jaggi AS, Singh N. Silymarin and its role in chronic diseases, Drug discovery from mother nature. Switzerland: Springer International Publishing. 2016; 25–44.
   Google Scholar
• Camini FC, Costa DC. Silymarin: not just another antioxidant. J Basic Clin Physiol Pharmacol. 2020;1: 1–12.
   Google Scholar
• Eo HJ, Park GH, Song HM, et al. Silymarin induces cyclin D1 proteasomal degradation via its phosphorylation of threonine-286 in human colorectal cancer cells. Int Immunopharmacol. 2015;24(1):1–6.
   PubMed Web of Science ®Google Scholar
• Li L, Zeng J, Gao Y, et al. Targeting silibinin in the antiproliferative pathway. Expert Opin Investig Drugs. 2010;19(2):243–255.
   PubMed Web of Science ®Google Scholar
• Bonifacio BV, da Silva PB, Dos Santos Ramos MA, et al. Nanotechnology-based drug delivery systems and herbal medicines: a review. Int J Nanomedicine. 2014;9:1.
   PubMed Web of Science ®Google Scholar
• Patra JK, Das G, Fraceto LF, et al. Nano based drug delivery systems: recent developments and future prospects. J Nanobiotechnology. 2018;16(1):71.
   PubMed Web of Science ®Google Scholar
• Zhang J, Misra R. Nanomaterials in microfluidics for disease diagnosis and therapy development. Mater Technol. 2019;34(2):92–116.
   Web of Science ®Google Scholar
• Vasir JK, Reddy MK, Labhasetwar VD. Nanosystems in drug targeting: opportunities and challenges. Curr Nanosci. 2005;1(1):47–64.
   Web of Science ®Google Scholar
• Ambwani S, Tandon R, Ambwani TK, et al. Current knowledge on nanodelivery systems and their beneficial applications in enhancing the efficacy of herbal drugs. J Exp Biol Agric Sci. 2018;6(1):87–107.
   Google Scholar
• Takke A, Shende P. Nanotherapeutic silibinin: an insight of phytomedicine in healthcare reformation, Nanomedicine: nanotechnology. Biol Med. 2019;21:102057.
   Google Scholar
• Di Costanzo A, Angelico R. Formulation strategies for enhancing the bioavailability of silymarin: the state of the art. Molecules. 2019;24(11):2155.
   PubMed Web of Science ®Google Scholar
• Ahmad U, Akhtar J, Singh SP, et al. Silymarin nanoemulsion against human hepatocellular carcinoma: development and optimization. Artif Cells Nanomed Biotechnol. 2018;46(2):231–241.
   PubMed Web of Science ®Google Scholar
• Patra JK, Das G, Fraceto LF, et al. Nano based drug delivery systems: recent developments and future prospects. J Nanobiotechnology. 2018;16(1):1–33.
   PubMed Web of Science ®Google Scholar
• Mu W, Chu Q, Liu Y, et al. A review on nano-based drug delivery system for cancer chemoimmunotherapy. Nano-Micro Lett. 2020;12(1):1–24.
   Web of Science ®Google Scholar
• Jin S-E, Jin H-E, Hong -S-S. Targeted delivery system of nanobiomaterials in anticancer therapy: from cells to clinics. Biomed Res Int. 2014;2014.
   Google Scholar
• Navya P, Kaphle A, Srinivas S, et al. Current trends and challenges in cancer management and therapy using designer nanomaterials. Nano Convergence. 2019;6(1):1–30.
   PubMedGoogle Scholar
• Maeda H, Nakamura H, Fang J. The EPR effect for macromolecular drug delivery to solid tumors: improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo. Adv Drug Deliv Rev. 2013;65(1):71–79.
   PubMed Web of Science ®Google Scholar
• Broz ML, Binnewies M, Boldajipour B, et al. Dissecting the tumor myeloid compartment reveals rare activating antigen-presenting cells critical for T cell immunity. Cancer Cell. 2014;26(5):638–652.
   PubMed Web of Science ®Google Scholar
• Matsumura Y, Maeda H. A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res. 1986;46(12 Part 1):6387–6392.
   PubMed Web of Science ®Google Scholar
• Bertrand N, Wu J, Xu X, et al. Cancer nanotechnology: the impact of passive and active targeting in the era of modern cancer biology. Adv Drug Deliv Rev. 2014;66:2–25.
   PubMed Web of Science ®Google Scholar
• Berrada M, Serreqi A, Dabbarh F, et al. A novel non-toxic camptothecin formulation for cancer chemotherapy. Biomaterials. 2005;26(14):2115–2120.
   PubMedGoogle Scholar
• Kirpotin DB, Drummond DC, Shao Y, et al. Antibody targeting of long-circulating lipidic nanoparticles does not increase tumor localization but does increase internalization in animal models. Cancer Res. 2006;66(13):6732–6740.
   PubMed Web of Science ®Google Scholar
• Yoo J, Park C, Yi G, et al. Active targeting strategies using biological ligands for nanoparticle drug delivery systems. Cancers (Basel). 2019;11(5):640.
   PubMed Web of Science ®Google Scholar
• Schmidt MM, Wittrup KD. A modeling analysis of the effects of molecular size and binding affinity on tumor targeting. Mol Cancer Ther. 2009;8(10):2861–2871.
   PubMed Web of Science ®Google Scholar
• Singh RP, Sharma G, Agrawal P, et al. Transferrin receptor targeted PLA-TPGS micelles improved efficacy and safety in docetaxel delivery. Int J Biol Macromol. 2016;83:335–344.
   PubMed Web of Science ®Google Scholar
• Hou J, Diao Y, Li W, et al. RGD peptide conjugation results in enhanced antitumor activity of PD0325901 against glioblastoma by both tumor-targeting delivery and combination therapy. Int J Pharm. 2016;505(1–2):329–340.
   PubMedGoogle Scholar
• Rogers L, Majer F, Sergeeva NN, et al. Synthesis and biological evaluation of Foscan® bile acid conjugates to target esophageal cancer cells. Bioorg Med Chem Lett. 2013;23(9):2495–2499.
   PubMedGoogle Scholar
• Yang Y, Zhu W, Cheng L, et al. Tumor microenvironment (TME)-activatable circular aptamer-PEG as an effective hierarchical-targeting molecular medicine for photodynamic therapy. Biomaterials. 2020;246:119971.
   PubMedGoogle Scholar
• Low PS, Henne WA, Doorneweerd DD. Discovery and development of folic-acid-based receptor targeting for imaging and therapy of cancer and inflammatory diseases. Acc Chem Res. 2008;41(1):120–129.
   PubMed Web of Science ®Google Scholar
• Křen V, Walterová D. Silybin and silymarin-new effects and applications. Biomed Pap. 2005;149(1):29–41.
   PubMedGoogle Scholar
• Nguyen H, Zhang S, Morris ME. Effect of flavonoids on MRP1-mediated transport in Panc-1 cells. J Pharm Sci. 2003;92(2):250–257.
   PubMed Web of Science ®Google Scholar
• Kaur M, Velmurugan B, Tyagi A, et al. Silibinin suppresses growth and induces apoptotic death of human colorectal carcinoma LoVo cells in culture and tumor xenograft. Mol Cancer Ther. 2009;8(8):2366–2374.
   PubMedGoogle Scholar
• Agarwal C, Singh RP, Dhanalakshmi S, et al. Silibinin upregulates the expression of cyclin-dependent kinase inhibitors and causes cell cycle arrest and apoptosis in human colon carcinoma HT-29 cells. Oncogene. 2003;22(51):8271–8282.
   PubMed Web of Science ®Google Scholar
• Li L, Gao Y, Zhang L, et al. Silibinin inhibits cell growth and induces apoptosis by caspase activation, down-regulating survivin and blocking EGFR–ERK activation in renal cell carcinoma. Cancer Lett. 2008;272(1):61–69.
   PubMedGoogle Scholar
• Wang H-J, Tashiro S-I, Onodera S, et al. Inhibition of insulin-like growth factor 1 receptor signaling enhanced silibinin-induced activation of death receptor and mitochondrial apoptotic pathways in human breast cancer MCF-7 cells. J Pharmacol Sci. 2008;107(3):260–269.
   PubMedGoogle Scholar
• Son Y-G, Kim EH, Kim JY, et al. Silibinin sensitizes human glioma cells to TRAIL-mediated apoptosis via DR5 up-regulation and down-regulation of c-FLIP and survivin. Cancer Res. 2007;67(17):8274–8284.
   PubMed Web of Science ®Google Scholar
• Kauntz H, Bousserouel S, Gossé F, et al. Silibinin triggers apoptotic signaling pathways and autophagic survival response in human colon adenocarcinoma cells and their derived metastatic cells. Apoptosis. 2011;16(10):1042.
   PubMed Web of Science ®Google Scholar
• Agarwal C, Tyagi A, Kaur M, et al. Silibinin inhibits constitutive activation of Stat3, and causes caspase activation and apoptotic death of human prostate carcinoma DU145 cells. Carcinogenesis. 2007;28(7):1463–1470.
   PubMedGoogle Scholar
• Garcia-Maceira P, Mateo J. Silibinin inhibits hypoxia-inducible factor-1α and mTOR/p70S6K/4E-BP1 signalling pathway in human cervical and hepatoma cancer cells: implications for anticancer therapy. Oncogene. 2009;28(3):313–324.
   PubMed Web of Science ®Google Scholar
• Kang L, Gao Z, Huang W, et al. Nanocarrier-mediated co-delivery of chemotherapeutic drugs and gene agents for cancer treatment. Acta Pharm Sin B. 2015;5(3):169–175.
   PubMed Web of Science ®Google Scholar
• Yap TA, Omlin A, De Bono JS. Development of therapeutic combinations targeting major cancer signaling pathways. J clin oncol. 2013;31(12):1592–1605.
   PubMed Web of Science ®Google Scholar
• Partridge AH, Burstein HJ, Winer EP. Side effects of chemotherapy and combined chemohormonal therapy in women with early-stage breast cancer. JNCI Monogr. 2001;2001(30):135–142.
   Google Scholar
• Lebaron S, Zeltzer LK, Lebaron C, et al. Chemotherapy side effects in pediatric oncology patients: drugs, age, and sex as risk factors. Med Pediatr Oncol. 1988;16(4):263–268.
   PubMedGoogle Scholar
• Blagosklonny MV. Overcoming limitations of natural anticancer drugs by combining with artificial agents. Trends Pharmacol Sci. 2005;26(2):77–81.
   PubMed Web of Science ®Google Scholar
• Pashaei-Asl F, Pashaei-Asl R, Khodadadi K, et al. Enhancement of anticancer activity by silibinin and paclitaxel combination on the ovarian cancer. Artif Cells Nanomed Biotechnol. 2018;46(7):1483–1487.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Ge Y, Ping X, et al. Synergistic apoptotic effects of silibinin in enhancing paclitaxel toxicity in human gastric cancer cell lines. Mol Med Rep. 2018;18(2):1835–1841.
   PubMedGoogle Scholar
• Dizaji MZ, Malehmir M, Ghavamzadeh A, et al. Synergistic effects of arsenic trioxide and silibinin on apoptosis and invasion in human glioblastoma U87MG cell line. Neurochem Res. 2012;37(2):370–380.
   PubMedGoogle Scholar
• Tyagi AK, Singh RP, Agarwal C, et al. Silibinin strongly synergizes human prostate carcinoma DU145 cells to doxorubicin-induced growth Inhibition, G2-M arrest, and apoptosis. Clin Cancer Res. 2002;8(11):3512–3519.
   PubMed Web of Science ®Google Scholar
• Singh RP, Mallikarjuna G, Sharma G, et al. Oral silibinin inhibits lung tumor growth in athymic nude mice and forms a novel chemocombination with doxorubicin targeting nuclear factor κB–mediated inducible chemoresistance. Clin Cancer Res. 2004;10(24):8641–8647.
   PubMedGoogle Scholar
• Rho JK, Choi YJ, Jeon B-S, et al. Combined treatment with silibinin and epidermal growth factor receptor tyrosine kinase inhibitors overcomes drug resistance caused by T790M mutation. Mol Cancer Ther. 2010;9(12):3233–3243.
   PubMedGoogle Scholar
• Tsai -C-C, Chuang T-W, Chen L-J, et al. Increase in apoptosis by combination of metformin with silibinin in human colorectal cancer cells. World J Gastroenterol. 2015;21(14):4169.
   PubMedGoogle Scholar
• Tyagi AK, Agarwal C, Chan DC, et al. Synergistic anti-cancer effects of silibinin with conventional cytotoxic agents doxorubicin, cisplatin and carboplatin against human breast carcinoma MCF-7 and MDA-MB468 cells. Oncol Rep. 2004;11(2):493–499.
   PubMed Web of Science ®Google Scholar
• Nejati-Koshki K, Akbarzadeh A, Pourhasan-Moghaddam M, et al. Inhibition of leptin and leptin receptor gene expression by silibinin-curcumin combination. Asian Pac J Cancer Prev. 2013;14(11):6595–6599.
   Google Scholar
• Akhter MH, Rizwanullah M, Ahmad J, et al. Nanocarriers in advanced drug targeting: setting novel paradigm in cancer therapeutics. Artif Cells Nanomed Biotechnol. 2018;46(5):873–884.
   PubMed Web of Science ®Google Scholar
• Senapati S, Mahanta AK, Kumar S, et al. Controlled drug delivery vehicles for cancer treatment and their performance. Signal Transduct Target Ther. 2018;3(1):1–19.
   PubMedGoogle Scholar
• Gabizon AA, Shmeeda H, Zalipsky S. Pros and cons of the liposome platform in cancer drug targeting. J Liposome Res. 2006;16(3):175–183.
   PubMed Web of Science ®Google Scholar
• Ochi MM, Amoabediny G, Rezayat SM, et al. 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 (Yakhteh). 2016;18(2):135.
   PubMed Web of Science ®Google Scholar
• Mahira S, Kommineni N, Husain GM, et al. 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.
   PubMed Web of Science ®Google Scholar
• Li Y, Yang D, Wang Y, et al. Co-delivery doxorubicin and silybin for anti-hepatoma via enhanced oral hepatic-targeted efficiency. Int J Nanomedicine. 2019;14:301.
   PubMedGoogle Scholar
• Han L, Guo K, Gu F, et al. Effects of silibinin‑loaded thermosensitive liposome‑microbubble complex on inhibiting rabbit liver VX2 tumors in sub‑hyperthermia fields. Exp Ther Med. 2018;15(2):1233–1240.
   PubMedGoogle Scholar
• Gharbavi M, Amani J, Kheiri-Manjili H, et al. Niosome: a promising nanocarrier for natural drug delivery through blood-brain barrier. Adv Pharmacol Sci. 2018;2018: 1–15 .
   Web of Science ®Google Scholar
• Sudheer P, Kaushik K. Review on niosomes-a novel approach for drug targeting. J Pharm Res. 2015;14(1):20–25.
   Google Scholar
• Amiri B, Ebrahimi-Far M, Saffari Z, et al. Preparation, characterization and cytotoxicity of silibinin-containing nanoniosomes in T47D human breast carcinoma cells. Asian Pac J Cancer Prev. 2016;17(8):3835–3838.
   PubMedGoogle Scholar
• Sajjadiyan SZ, Ghadernejad H, Milani AT, et al. Preparation of silibinin loaded pegylatedniosomal nanoparticles and investigation of its effect on MCF-10A human breast cancer cell line. Der Pharmacia Lettre. 2016;8(16):70–75.
   Google Scholar
• Yazdi Rouholamini SE, Moghassemi S, Maharat Z, et al. 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.
   PubMed Web of Science ®Google Scholar
• Permyakova N, Zheltonozhskaya T, Beregova T, et al. Micellar nanocarriers for anticancer drug melanin. Mol Cryst Liq Cryst. 2016;640(1):122–133.
   Web of Science ®Google Scholar
• Choudhury H, Maheshwari R, Pandey M, et al. Advanced nanoscale carrier-based approaches to overcome biopharmaceutical issues associated with anticancer drug ‘Etoposide. Mater Sci Eng C. 2020;106:110275.
   PubMedGoogle Scholar
• Zhang Y, Huang Y, Li S. Polymeric micelles: nanocarriers for cancer-targeted drug delivery. Aaps Pharmscitech. 2014;15(4):862–871.
   PubMed Web of Science ®Google Scholar
• Keskin D, Tezcaner A. Micelles as delivery system for cancer treatment. Curr Pharm Des. 2017;23(35):5230–5241.
   PubMedGoogle Scholar
• Varela-Moreira A, Shi Y, Fens MH, et al. Clinical application of polymeric micelles for the treatment of cancer. Mater Chem Front. 2017;1(8):1485–1501.
   Web of Science ®Google Scholar
• Hanafy NA, El-Kemary M, Leporatti S. Micelles structure development as a strategy to improve smart cancer therapy. Cancers (Basel). 2018;10(7):238.
   Web of Science ®Google Scholar
• Sonar YA, Mahajan HS. Development of glucosamine functionaliZed micelles as a potential drug delivery system for targeting to brain. Mater Technol. 2020;35(2):125–133.
   Web of Science ®Google Scholar
• Keshari P, Sonar Y, Mahajan H. Curcumin loaded TPGS micelles for nose to brain drug delivery: in vitro and in vivo studies. Mater Technol. 2019;34(7):423–432.
   Web of Science ®Google Scholar
• Scavo MP, Gentile E, Wolfram J, et al. Multistage vector delivery of sulindac and silymarin for prevention of colon cancer. Colloids Surface B . 2015;136:694–703. DOI:10.1016/j.colsurfb.2015.10.005
   PubMedGoogle Scholar
• El-Far M, Salah N, Essam A, et al. Silymarin nanoformulation as potential anticancer agent in experimental Ehrlich ascites carcinoma-bearing animals. Nanomedicine. 2018;13(15):1865–1858.
   PubMed Web of Science ®Google Scholar
• Dong X-Y, Lang T-Q, Yin Q, et al. Co-delivery of docetaxel and silibinin using pH-sensitive micelles improves therapy of metastatic breast cancer. Acta Pharmacol Sin. 2017;38(12):1655–1662.
   PubMedGoogle Scholar
• Soodvilai S, Tipparos W, Rangsimawong W, et al. Effects of silymarin-loaded amphiphilic chitosan polymeric micelles on the renal toxicity and anticancer activity of cisplatin. Pharm Dev Technol. 2019;24(8):927–934.
   PubMed Web of Science ®Google Scholar
• Rad AH, Asiaee F, Jafari S, et al. Poly (ethylene glycol)-poly (ε-caprolactone)-based micelles for solubilization and tumor-targeted delivery of silibinin. Bioimpacts. 2020;10(2):87.
   PubMed Web of Science ®Google Scholar
• Tan JM, Karthivashan G, Arulselvan P, et al. Characterization and in vitro sustained release of silibinin from pH responsive carbon nanotube-based drug delivery system. J Nanomater. 2014;2014: 1–10 .
   Google Scholar
• Tan JM, Karthivashan G, Abd Gani S, et al. 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.
   PubMedGoogle Scholar
• Jagdevappa P, Prashant G, Ravindra K, et al. Applications of solid lipid nanoparticle in novel drug delivery system. Br Biomed Bull. 2013;1(2):103–118.
   Google Scholar
• Hasan AA, Madkor H, Wageh S. Formulation and evaluation of metformin hydrochloride-loaded niosomes as controlled release drug delivery system. Drug Deliv. 2013;20(3–4):120–126.
   PubMed Web of Science ®Google Scholar
• Battaglia L, Ugazio E. Lipid nano-and microparticles: an overview of patent-related research. J Nanomater. 2019;1–22.
   Google Scholar
• Patil TS, Deshpande AS. Design, development, and characterisation of clofazimine-loaded mannosylated nanostructured lipid carriers: 33-Box-Behnken design approach. Mater Technol. 2020; 36(8) : 1–16.
   Google Scholar
• Nordin N, Yeap SK, Rahman HS, et al. In vitro cytotoxicity and anticancer effects of citral nanostructured lipid carrier on MDA MBA-231 human breast cancer cells. Sci Rep. 2019;9(1):1–19.
   PubMedGoogle Scholar
• Pardeshi CV, Belgamwar VS. Improved brain pharmacokinetics following intranasal administration of N, N, N-trimethyl chitosan tailored mucoadhesive NLCs. Mater Technol. 2020;35(5):249–266.
   Web of Science ®Google Scholar
• Singh P, Singh M, Kanoujia J, et al. Process optimization and photostability of silymarin nanostructured lipid carriers: effect on UV-irradiated rat skin and SK-MEL 2 cell line. Drug Deliv Transl Res. 2016;6(5):597–609.
   PubMed Web of Science ®Google Scholar
• Singh P, Arya M, Kanoujia J, et al. Design of topical nanostructured lipid carrier of silymarin and its effect on 7, 12-dimethylbenz [a] anthracene (DMBA) induced cellular differentiation in mouse skin. RSC Adv. 2016;6(88):84965–84977.
   Web of Science ®Google Scholar
• Iqbal B, Ali J, Ganguli M, et al. Silymarin-loaded nanostructured lipid carrier gel for the treatment of skin cancer. Nanomedicine. 2019;14(9):1077–1093.
   PubMedGoogle Scholar
• Fofaria NM, Qhattal HSS, Liu X, et al. Nanoemulsion formulations for anti-cancer agent piplartine—Characterization, toxicological, pharmacokinetics and efficacy studies. Int J Pharm. 2016;498(1–2):12–22.
   PubMedGoogle Scholar
• Yen -C-C, Chen Y-C, Wu M-T, et al. Nanoemulsion as a strategy for improving the oral bioavailability and anti-inflammatory activity of andrographolide. Int J Nanomedicine. 2018;13:669.
   PubMed Web of Science ®Google Scholar
• Adhikari M, Kaushik N, Ghimire B, et al. Cold atmospheric plasma and silymarin nanoemulsion synergistically inhibits human melanoma tumorigenesis via targeting HGF/c-MET downstream pathway. Cell Commun Signaling. 2019;17(1):52.
   PubMedGoogle Scholar
• Patel VR, Agrawal Y. Nanosuspension: an approach to enhance solubility of drugs. J Adv Pharm Technol Res. 2011;2(2):81.
   PubMedGoogle Scholar
• Zheng D, Wang Y, Zhang D, et al. In vitro antitumor activity of silybin nanosuspension in PC-3 cells. Cancer Lett. 2011;307(2):158–164.
   PubMed Web of Science ®Google Scholar
• Elahi N, Kamali M, Baghersad MH. Recent biomedical applications of gold nanoparticles: a review. Talanta. 2018;184:537–556.
   PubMed Web of Science ®Google Scholar
• Amirsaadat S, Pilehvar-Soltanahmadi Y, Zarghami F, et al. Silibinin-loaded magnetic nanoparticles inhibit hTERT gene expression and proliferation of lung cancer cells. Artif Cells Nanomed Biotechnol. 2017;45(8):1649–1656.
   PubMed Web of Science ®Google Scholar
• Paulpandi M. 78P In vivo activation of mitochondrial pathway and cell cycle arrest through silymarin loaded iron nanoparticles as proficient nanocomplex system for triple negative breast cancer therapy. Ann Oncol. 2017;28(suppl_10):mdx655. 020.
   Google Scholar
• Patil JS, Dhadde SB, Chandakavathe BN. Nanostructure drug delivery system is an option to solve antimicrobial drug resistance: perspective review, characterization and biology of nanomaterials for drug delivery. Amsterdam, Netherlands: Elsevier; 2019. p. 165–197.
   Google Scholar
• Patil KD, Bagade S, Bonde S. QbD-enabled stability-indicating assay method for the estimation of linezolid in newly developed gelatin nanoparticles for anti-tubercular therapy. Chromatographia. 2020;83(8):963–973.
   Google Scholar
• Gohulkumar M, Gurushankar K, Prasad NR, et al. Enhanced cytotoxicity and apoptosis-induced anticancer effect of silibinin-loaded nanoparticles in oral carcinoma (KB) cells. Mater Sci Eng C. 2014;41:274–282.
   PubMed Web of Science ®Google Scholar
• Pooja D, Bikkina DJB, Kulhari H, et al. Fabrication, characterization and bioevaluation of silibinin loaded chitosan nanoparticles. Int J Biol Macromol. 2014;69:267–273.
   PubMed Web of Science ®Google Scholar
• Snima K, Arunkumar P, Jayakumar R, et al. Silymarin encapsulated poly (D, L-lactic-co-glycolic acid) nanoparticles: a prospective candidate for prostate cancer therapy. J Biomed Nanotechnol. 2014;10(4):559–570.
   PubMedGoogle Scholar
• Guan X-L, Zhao S-Z, Hou R-J, et al. Pharmacokinetics of silybin nanoparticles in mice bearing SKOV-3 human ovarian carcinoma xenocraft. Int J Clin Exp Med. 2015;8(10):17406.
   PubMed Web of Science ®Google Scholar
• Kuen CY, Fakurazi S, Othman SS, et al. 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. 2017;7(11):379.
   Web of Science ®Google Scholar
• Alipour M, Reza Bigdeli M, Aligholi H, et al. Sustained release of silibinin‐loaded chitosan nanoparticle induced apoptosis in glioma cells. J Biomed Mater Res A. 2020;108(3):458–469.
   PubMedGoogle Scholar
• Zhang H, Wang C-B, Liu J-L. Silybin nanoparticles for liver cancer: development, optimization and in vitro–in vivo evaluation. J BUON. 2016;21(3):633–644.
   PubMed Web of Science ®Google Scholar
• Radu I-C, Hudita A, Zaharia C, et al. Poly (hydroxybutyrate-co-hydroxyvalerate)(PHBHV) nanocarriers for silymarin release as adjuvant therapy in colo-rectal cancer. Front Pharmacol. 2017;8:508.
   PubMedGoogle Scholar
• Liu Y, Xie X, Hou X, et al. Functional oral nanoparticles for delivering silibinin and cryptotanshinone against breast cancer lung metastasis. J Nanobiotechnology. 2020;18(1):1–15.
   PubMedGoogle Scholar
• Huo M, Wang H, Zhang Y, et al. Co-delivery of silybin and paclitaxel by dextran-based nanoparticles for effective anti-tumor treatment through chemotherapy sensitization and microenvironment modulation. J Control Release. 2020;321:198–210.
   PubMed Web of Science ®Google Scholar
• Sun Z, Song C, Wang C, et al. Hydrogel-based controlled drug delivery for cancer treatment: a review. Mol Pharm. 2019;17(2):373–391.
   Google Scholar
• Oliva N, Conde J, Wang K, et al. Designing hydrogels for on-demand therapy. Acc Chem Res. 2017;50(4):669–679.
   PubMed Web of Science ®Google Scholar
• Ahmad MZ, Alkahtani SA, Akhter S, et al. Progress in nanotechnology-based drug carrier in designing of curcumin nanomedicines for cancer therapy: current state-of-the-art. J Drug Target. 2016;24(4):273–293.
   PubMed Web of Science ®Google Scholar
• Umaredkar AA, Dangre PV, Mahapatra DK, et al. Fabrication of chitosan-alginate polyelectrolyte complexed hydrogel for controlled release of cilnidipine: a statistical design approach. Mater Technol. 2020;35(11–12):697–707.
   Web of Science ®Google Scholar
• Cho J-K, Park JW, Song S-C. Injectable and biodegradable poly (organophosphazene) gel containing silibinin: its physicochemical properties and anticancer activity. J Pharm Sci. 2012;101(7):2382–2391.
   PubMedGoogle Scholar
• Makhmalzadeh BS, Molavi O, Vakili MR, et al. Functionalized caprolactone-polyethylene glycol based thermo-responsive hydrogels of silibinin for the treatment of malignant melanoma. J Pharm Pharm Sci. 2018;21:143–159.
   PubMed Web of Science ®Google Scholar
• Entezari M, Atabi F. Preparation and characterization of myristoylated chitosan nanogel as carrier of silibinin for breast cancer therapy. Galen Med J. 2017;6(2):136–144.
   Google Scholar
• Marchiori MCL, Rigon C, Camponogara C, et al. Hydrogel containing silibinin-loaded pomegranate oil based nanocapsules exhibits anti-inflammatory effects on skin damage UVB radiation-induced in mice. J Photochem Photobiol B Biol. 2017;170:25–32.
   PubMed Web of Science ®Google Scholar
• Flaig TW, Glodé M, Gustafson D, et al. A study of high‐dose oral silybin‐phytosome followed by prostatectomy in patients with localized prostate cancer. Prostate. 2010;70(8):848–855.
   PubMed Web of Science ®Google Scholar
• NCT00487721 (2010). The Effect of High-dose Silybin-phytosome in Men With Prostate Cancer. Available online at https://www.clinicaltrials.gov/ct2/show/NCT00487721 (Accessed April 9, 2021)
   Google Scholar
• NCT02146118 (2014) A phase II study to assess efficacy of combined treatment with erlotinib (tarceva) and silybin-phytosome (siliphos) in patients with EGFR mutant lung adenocarcinoma. Available online at https://www.clinicaltrials.gov/ct2/show/NCT02146118 (Accessed April 9, 2021)
   Google Scholar
• NCT01129570 (2013) Siliphos in Advanced Hepatocellular Carcinoma. Available online at https://www.clinicaltrials.gov/ct2/show/NCT01129570 (Accessed April 9, 2021)
   Google Scholar