The Synthesis, Characterization and Determination of Antioxidant Activity of Rutin Loaded Chitosan Nanoparticles

Yıl 2020, Cilt: 3 Sayı: 2, 93 - 99, 29.12.2020

Gizem Beyoğlu Özlem Araç Derya Taşkın Pelin Pelit Arayıcı Kadriye Kızılbey Serap Derman

Öz

Rutin, one of the quercetin glycosides, is a flavanoid mainly found in different parts of plants such as fruit peels, leaves, flowers and roots. Although it has antioxidant, antimicrobial and chelating properties due to its chemical structure and its bioavailability in living system is very low due to its poor solubility. In this study, to increase the bioavailability of the rutin molecule, rutin loaded chitosan nanoparticles were synthesized by ionic gelling method and their in vitro releasing studies and antioxidant activities were investigated. The encapsulation efficiency and effective loading capacity of the rutin loaded chitosan nanoparticles were analyzed by UV-Vis spectrophotometer, and particle size, multiple distribution index and zeta potential values were analyzed by Photon Correlation Spectroscopy. Polymer-active molecule interactions of these nanoparticles were examined by FT-IR spectroscopy. The optimum nanoparticle for releasing studies was determined as Rutin-loaded Chitosan Nanoparticles3 (R-Chi NPs3) considering the encapsulation efficiency and effective loading capacity. In-vitro releasing study was continued for 17 days and at the end of this time 88.8 % rutin release was observed. The antioxidant activity study of the synthesized nanoparticles was carried out by DPPH method, and the antioxidant activity of R-Chi NPs3 nanoparticles increased due to increasing concentration and it was determined that they showed 88.1% antioxidant activity with 0.8 mg/mL R-Chi NPs3 concentration. This study is a research study showing that advanced biotechnological systems that can make controlled release can be designed to increase the effects of molecules with low bioavailability.

Anahtar Kelimeler

Rutin, Chitosan, Nanoparticle, Antioxidant Activity

Rutin Yüklü Kitosan Nanopartiküllerinin Sentezi, Karakterizasyonu ve Antioksidan Aktivitesinin Değerlendirilmesi

Öz

Kuersetin glikozitlerinden biri olan rutin esas olarak meyve kabukları, yaprakları, çiçekleri ve kökleri gibi bitkilerin farklı kısımlarında bulunan bir flavanoiddir. Kimyasal yapısı nedeniyle antioksidan, antimikrobiyal ve şelatlayıcı özellikleri bulunan rutin molekülünün zayıf çözünürlüğü nedeniyle canlı sistemde biyoyararlanımı oldukça düşüktür. Bu çalışmada, rutin molekülünün biyoyararlanımını arttırmak için iyonik jelleşme yöntemi kullanılarak rutin yüklü kitosan nanopartikülleri sentezlenmiş ve in vitro ortamda salımları ve antioksidan aktiviteleri araştırılmıştır. Üretilen rutin yüklü kitosan nanopartiküllerin enkapsülasyon etkinliği ve etken yükleme kapasitesi UV-Vis spektrofotometre kullanılarak; parçacık boyutu, çoklu dağılım indeksi ve zeta potansiyel değerleri ise Foton Korelasyon Spektroskopisi ile analiz edilmiştir. Bu nanopartiküllerdeki polimer-etken molekül etkileşimleri FT-IR ile incelenmiştir. Enkapsülasyon etkinliği ve etken yükleme kapasitesi göz önüne alınarak salım deneyleri için optimum nanopartikül Rutin yüklü Kitosan Nanopartikül3 (R-Chi NPs3) olarak belirlenmiştir. In vitro salım çalışması 17 gün devam ettirilmiş ve bu sürenin sonunda %88.8 oranında rutin salımı gözlenmiştir. Sentezlenen nanopartiküllerin antioksidan aktivite çalışması ise DPPH yöntemi ile gerçekleştirilmiş olup R-Chi NPs3 nanopartiküllerin antioksidan aktivitesinin artan konsantrasyona bağlı olarak arttığı ve 0.8 mg/mL R-Chi NPs3 içeren örneğin %88.1 antioksidan aktivite gösterdiği belirlenmiştir. Bu çalışma, biyoyararlanımı düşük olan moleküllerin etkilerini arttırmak için kontrollü salım yapabilecek gelişmiş biyoteknolojik sistemlerin tasarlanabileceğini gösteren bir araştırma niteliğindedir.

Anahtar Kelimeler

Rutin, Kitosan, Nanopartikül, Antioksidan Aktivite

Kaynakça

• Referans1 Agrawal, R. D., A. A. Tatode, N. R. Rarokar and M. J. Umekar (2020). "Polymeric micelle as a nanocarrier for delivery of therapeutic agents: A comprehensive review." Journal of Drug Delivery and Therapeutics 10(1-s): 191-195.
• Referans2 Ananth, D. A., A. Rameshkumar, R. Jeyadevi, S. Jagadeeswari, N. Nagarajan, R. Renganathan and T. Sivasudha (2015). "Antibacterial potential of rutin conjugated with thioglycolic acid capped cadmium telluride quantum dots (TGA-CdTe QDs)." Spectrochimica acta part A: molecular and biomolecular spectroscopy 138: 684-692.
• Referans3 Bernkop-Schnürch, A. and S. Dünnhaupt (2012). "Chitosan-based drug delivery systems." European journal of pharmaceutics and biopharmaceutics 81(3): 463-469.
• Referans4 Bilia, A. R., B. Isacchi, C. Righeschi, C. Guccione and M. C. Bergonzi (2014). "Flavonoids loaded in nanocarriers: an opportunity to increase oral bioavailability and bioefficacy." Food and Nutrition Sciences 2014.
• Referans5 Blois, M. S. (1958). "Antioxidant determinations by the use of a stable free radical." Nature 181(4617): 1199-1200.
• Referans6 Budhian, A., S. J. Siegel and K. I. Winey (2007). "Haloperidol-loaded PLGA nanoparticles: systematic study of particle size and drug content." International journal of pharmaceutics 336(2): 367-375.
• Referans7 Cun, D., D. K. Jensen, M. J. Maltesen, M. Bunker, P. Whiteside, D. Scurr, C. Foged and H. M. Nielsen (2011). "High loading efficiency and sustained release of siRNA encapsulated in PLGA nanoparticles: quality by design optimization and characterization." European journal of pharmaceutics and biopharmaceutics 77(1): 26-35.
• Referans8 Davidson, R. S. and G. Kehoe (2015). Methods for modulating dissolution, bioavailability, bioequivalence and drug delivery profile of thin film drug delivery systems, controlled-release thin film dosage formats, and methods for their manufacture and use, Google Patents.
• Referans9 De Queiroz Antonino, R. S. C., L. Fook, B. R. Paschoal, V. A. De Oliveira Lima, R. Í. De Farias Rached, E. P. N. Lima, R. J. Da Silva Lima, C. A. Peniche Covas and M. V. Lia Fook (2017). "Preparation and characterization of chitosan obtained from shells of shrimp (Litopenaeus vannamei Boone)." Marine drugs 15(5): 141.
• Referans10 Derman, S. (2015). "Caffeic acid phenethyl ester loaded PLGA nanoparticles: effect of various process parameters on reaction yield, encapsulation efficiency, and particle size." Journal of Nanomaterials 2015.
• Referans11 Derman, S., K. Kızılbey and Z. M. Akdeste (2013). "Polymeric nanoparticles." Sigma 31: 107-120.
• Referans12 Ertugen, E., A. Tunçel and F. Yurt (2020). "Docetaxel loaded human serum albumin nanoparticles; synthesis, characterization, and potential of nuclear imaging of prostate cancer." Journal of Drug Delivery Science and Technology 55: 101410.
• Referans13 Frutos, M. J., L. Rincón-Frutos and E. Valero-Cases (2019). Rutin. Nonvitamin and Nonmineral Nutritional Supplements, Elsevier: 111-117.
• Referans14 Hao, S., et al., Rapid preparation of pH-sensitive polymeric nanoparticle with high loading capacity using electrospray for oral drug delivery. Materials Science and Engineering: C, 2013. 33(8): p. 4562-4567.
• Referans15 Hooresfand, Z., S. Ghanbarzadeh and H. Hamishehkar (2015). "Preparation and characterization of rutin-loaded nanophytosomes." Pharm Sci 21(3): 145-151.
• Referans16 Kim, H. P., K. H. Son, H. W. Chang and S. S. Kang (2004). "Anti-inflammatory plant flavonoids and cellular action mechanisms." Journal of pharmacological sciences: 0411110005-0411110005.
• Referans17 Kirik, T. and K. Kızılbey "Rutin yüklü PLGA Nanopartiküller; Farklı Yöntemler Kullanılarak Sentezi ve Karakterizasyonu." Iğdır Üniversitesi Fen Bilimleri Enstitüsü Dergisi 9(2): 922-932.
• Referans18 Kızılbey, K. (2019). "Optimization of Rutin-Loaded PLGA Nanoparticles Synthesized by Single-Emulsion Solvent Evaporation Method." ACS Omega 4(1): 555-562.
• Referans19 Kreft, I., N. Fabjan and K. Yasumoto (2006). "Rutin content in buckwheat (Fagopyrum esculentum Moench) food materials and products." Food chemistry 98(3): 508-512.
• Referans20 Kumar, A., H. M. Mansour, A. Friedman and E. R. Blough (2013). Nanomedicine in drug delivery, CRC Press.
• Referans21 Lawrie, G., I. Keen, B. Drew, A. Chandler-Temple, L. Rintoul, P. Fredericks and L. Grøndahl (2007). "Interactions between alginate and chitosan biopolymers characterized using FTIR and XPS." Biomacromolecules 8(8): 2533-2541.
• Referans22 Nagarwal, R. C., S. Kant, P. Singh, P. Maiti and J. Pandit (2009). "Polymeric nanoparticulate system: a potential approach for ocular drug delivery." Journal of Controlled Release 136(1): 2-13.
• Referans23 Nguyen, T. A., B. Liu, J. Zhao, D. S. Thomas and J. M. Hook (2013). "An investigation into the supramolecular structure, solubility, stability and antioxidant activity of rutin/cyclodextrin inclusion complex." Food chemistry 136(1): 186-192.
• Referans24 Peniche, H. and C. Peniche (2011). "Chitosan nanoparticles: a contribution to nanomedicine." Polymer International 60(6): 883-889.
• Referans25 Pilorget, A., V. Berthet, J. Luis, A. Moghrabi, B. Annabi and R. Béliveau (2003). "Medulloblastoma cell invasion is inhibited by green tea (−) epigallocatechin‐3‐gallate." Journal of cellular biochemistry 90(4): 745-755.
• Referans26 Qi, L., Z. Xu, X. Jiang, C. Hu and X. Zou (2004). "Preparation and antibacterial activity of chitosan nanoparticles." Carbohydrate research 339(16): 2693-2700.
• Referans27 Sharma, S., A. Ali, J. Ali, J. K. Sahni and S. Baboota (2013). "Rutin: therapeutic potential and recent advances in drug delivery." Expert opinion on investigational drugs 22(8): 1063-1079.
• Referans28 Sun, W., S. Mao, Y. Wang, V. B. Junyaprasert, T. Zhang, L. Na and J. Wang (2010). "Bioadhesion and oral absorption of enoxaparin nanocomplexes." International journal of pharmaceutics 386(1-2): 275-281.
• Referans29 Yeo, Y. and K. Park (2004). "Control of encapsulation efficiency and initial burst in polymeric microparticle systems." Archives of pharmacal research 27(1): 1.
• Referans30 Zandi, K., B. T. Teoh, S. S. Sam, P. F. Wong, M. R. Mustafa and S. AbuBakar (2011). "In vitro antiviral activity of fisetin, rutin and naringenin against dengue virus type-2." Journal of Medicinal Plants Research 5(23): 5534-5539.