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Preparation and Characterization of Myristoylated Chitosan Nanogel as Carrier of Silibinin for Breast Cancer Therapy

Maliheh Entezari, Fereshteh Atabi

Background: Biopolymer has been known to have compatibility; nontoxic nature and degradation behavior. Chitosan (CS) is being widely used in various biomedical and pharmaceutical applications and serves as a drug carrier. Nanotechnology has emerged as tumor cell target therapy and increase drug bioavailability. One of the most common and important models of cancer in women is breast cancer, which is the fifth most common death reason. Silibinin (SIL) as a flavonolignan, has demonstrated anticancer effects against various human cancer cells, such as breast cancer. Materials and Methods: Myristoylated CS (MCS) nanoparticles were prepared on the base of 9:1 ratio related to CS: Myristate and loaded with SIL, for the first time. Then in vitro loading and releasing capacity of nano drug were evaluated. The nanogel structure and its derivatives were characterized by different biophysical methods. The MCF-7 breast cancer cell line and human umbilical vein endothelial cells (HUVEC) cell lines were incubated with 100, 150, and 200μg/ml of SIL and nanoSIL. Afterward cell cytotoxicity was measured by MTT assay. Lethal dose 50 (LD50) or IC50 was measured by Pharm software. Results: Compared to HUVEC as normal cells, the proliferation of MCF-7 cells were significantly inhibited (P<0.01) by SIL and nano-SIL in a concentration-related manner in defining times (P<0.05). SIL-loaded nanogels were more effective than SIL alone (P<0.01). The mean size of MCS particles was about 20nm. The MCS nanogels were spheral and homogen with a dense surface. The loading efficiency was obtained about 85-95%. Conclusions: It seems the obtained MCS nanogel can play a real and important role as a suitable drug carrier with a high loading capacity to treat cancerous cells with the least side effect. [GMJ.2017;6(2):136-44]

Chitosan; Myristoylated; Silibinin; Nanogel; Breast Cancer

Entezari M, Mokhtari MJ, Hashemi M. Evaluation of Silibinin on the Viability of MCF-7 Human Breast Adenocarcinoma and HUVEC (Human Umbilical Vein Endothelial) cell lines. Advanced Studies in Biology. 2011;3(6):283-8.

Singh RP, Raina K, Sharma G, Agarwal R. Silibinin inhibits established prostate tumor growth, progression, invasion, and metastasis and suppresses tumor angiogenesis and epithelial-mesenchymal transition in transgenic adenocarcinoma of the mouse prostate model mice. Clin Canc Res. 2009; (14): 7773-80.

Bravo-Osuna I, Vauthier C, Chacun H, Ponchel G. Specific permeability modulation of intestinal paracellular pathway by Chitosan -poly (isobutylcyanoacrylate) core-shell nanoparticles. Eur J Pharm Biopharm. 2008; (69):436-44.

Rees M, Moghimi SM. Nanotechnology: From fundamental concepts to clinical applications for healthy aging. Maturitas. 2012; 73(1):1-4. Elsevier.

Sonia TA, Sharma CP. Chitosan and its derivatives for drug delivery perspective. In: AnonymousChitosan for Biomaterials I Adv Polym Sci. 2011; (243): 23-53.Springer.

Raj L, Chauhan GS, Azmi W, Ahn JH, Manu J. Kinetics study of invertase covalently linked to a new functional nanogel. Bioresour Technol. 2011; (102): 2177-84.

Hoare T, Sivakumaran D, Stefanescu CF, Lawlor MW, Kohane DS. Nanogel scavengers for drugs: Local anesthetic uptake by thermoresponsive nanogels. Acta Biomat. 2012; (8): 1450-58.

Yang X, Zhang X, Liu Z, Ma Y, Huang Y, Chen Y. High-efficiency loading and controlled release of doxorubicin hydrochloride on graphene oxide. J Physical Chem. 2008; (112): 17554-8.

Morris GA, Castile J, Smith A, Adams GG, Harding SE. The effect of prolonged storage at different temperatures on the particle size distribution of tripolyphosphate (TPP)-Chitosan nanoparticles. Carbohydr Polym. 2011; (84): 1430-4.

Kim YT, Yum S, Heo JS, Kim W, Jung Y, Kim YM. Dithiocarbamate Chitosan as a potential polymeric matrix for controlled drug release. Drug Dev Ind Pharm. 2013; (40):192-200.

Rinaudo M. Chitin and Chitosan : properties and applications. Prog Polymer Sci. 2006; (31): 603-32.

Bresolin JÑR, Largura MC, Dalri CC, Hoffer Gr, Rodrigues CvA, Lucinda-Silva RM. Spray-dried O-carboxymethyl Chitosan as potential hydrophilic matrix tablet for sustained release of drug. Drug Dev Ind Pharm. 2013; (40): 503-10.

Singla N, Sharma R, Bhardwaj TR. Design, Synthesis and In-Vitro Evaluation of Polymer-linked Prodrug of Methotrexate for the Targeted Delivery to the Colon. Lett Drug Des Discov. 2014; (11): 601-10.

Win PP, Shin-Ya Y, Hong KJ, Kajiuchi T. Formulation and characterization of pH sensitive drug carrier based on phosphorylated Chitosan (PCS). Carbohydr. Polym. 2003; (53): 305-10.

Rossi S, Ferrari F, Bonferoni MC, Sandri G, Faccendini A, Puccio A, et al. Comparison of poloxamer-and Chitosan -based thermally sensitive gels for the treatment of vaginal mucositis. Drug Dev Ind Pharm. 2013; (40): 352-60

Aranaz I, Harris R, Heras A. Chitosan amphiphilic derivatives. Chemistry and applications. Curr Organic Chem. 2010; (14): 308.

Anitha A, Deepa N, Chennazhi KP, Nair SV, Tamura H, Jayakumar R. Development of mucoadhesive thiolated Chitosan nanoparticles for biomedical applications. Carbohydr Polym. 2011; (83): 66-73.

Morris GA, Kok SM, Harding SE, Adams GG. Polysaccharide drug delivery systems based on pectin and Chitosan. Biotechn Genet Engin Rev. 2010; 27:257-84.

Tsai ML, Chen RH, Bai SW, Chen WY. The storage stability of Chitosan /tripolyphosphate nanoparticles in a phosphate buffer. Carbohydr Polym. 2011; (84): 756-61.

Arias JÑL, Martonez-Soler GI, Lopez-Viota M, Ruiz MÒA. Formulation of Chitosan nanoparticles loaded with metronidazole for the treatment of infectious diseases. Lett Drug Des Discov. 2010; (7): 70-8.

Zhang H, Oh M, Allen C, Kumacheva E. Monodisperse Chitosan nanoparticles for mucosal drug delivery. Biomacromolecules. 2004; (5): 2461-8.

Atabi F, Gargari SLM, Hashemi M, Yaghmaei P. Doxorubicin Loaded DNA Aptamer Linked Myristilated Chitosan Nanogel for Targeted Drug Delivery to Prostate Cancer. IJPR. 2017; 16(1): 35-49.

Tsai ML, Bai SW, Chen RH. Cavitation effects versus stretch effects resulted in different size and polydispersity of ionotropic gelation Chitosan GÇôsodium tripolyphosphate nanoparticle. Carbohydr Polym. 2008; (71): 448-57.

Wang C, Mallela J, Garapati US, Ravi S, Chinnasamy V, Girard Y, et al. A Chitosan -modified graphene nanogel for noninvasive controlled drug release. Nanomedicine: Nanotech Bio Med. 2013 (9): 903-11.

Jayakumar R, Nair A, Rejinold NS, Maya S, Nair SV. Doxorubicin-loaded pH-responsive chitin nanogels for drug delivery to cancer cells. Carbohyd Polym. 2012; (87): 2352-6.

Ibezim EC, Andrade CT, Marcia C, Barretto B, Odimegwu DC, de Lima FF. Ionically Cross-linked Chitosan /Tripolyphosphate Microparticles for the Controlled Delivery of Pyrimethamine. Ibnosina J Med Biomed Sci. 2011 (3).

Xu X, Chen X, Ma PÂ, Wang X, Jing X. The release behavior of doxorubicin hydrochloride from medicated fibers prepared by emulsion-electrospinning. Eur J Pharm Biopharm. 2008; (70): 165-70.

Bakhshayesh M, Zaker F, Hashemi M, Katebi M, Solaimani M. TGF- β1-mediated apoptosis associated with SMAD-dependent mitochondrial Bcl-2 expression. Clin Lymphoma Myeloma Leuk. 2012;12(2):138-43.

Saliani N, Darabi M, Yousefi B, Baradaran B, Kh

aniani MS, Darabi M, et al. PPARγ agonist-induced alterations in Δ6-desaturase and stearoyl-CoA desaturase 1: Role of MEK/ERK1/2 pathway. World J Hepatol. 2013;5(4):220-5.

Taranejoo S, Janmaleki M, Rafienia M, Kamali M, Mansouri M. Chitosan microparticles loaded with exotoxin A subunit antigen for intranasal vaccination against Pseudomonas aeruginosa: An in vitro study. Carbohyd Polym. 2011;1861(83): 1854-61.

Shahsavari S, Vasheghani-Farahani E, Ardjmand M, Abedin Dorkoosh F. Modeling of Drug Released from Acyclovir Nanoparticles Based on Artificial Neural Networks. Lett Drug Des Discov. 2014; (11): 174-83.

Cao Y, Gu Y, Liu L, Yang Y, Zhao P, Su P, et al. Reversion of multidrug resistance using self-organized nanoparticles holding both doxorubicin and targeting moiety. Lett Drug Des Discov. 2010; (7): 500-6.

Mitra T, Sailakshmi G, Gnanamani A, Mandal AB. Studies on Cross-linking of succinic acid with Chitosan /collagen. Mat Res. 2013; (16): 755-65.

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