Biyouyumlu Polimerik Kürelerden 5-Fluorourasilin Kontrollü Salımı

Yıl 2022, Cilt: 22 Sayı: 2, 366 - 376, 30.04.2022

Merve Olukman Şahin , Oya Şanlı

https://doi.org/10.35414/akufemubid.1066566

Cited By: 1

Öz

Primidin analoğu olan 5-Fluorourasil (5-FU) çok çeşitli kanserlerin (meme, kolorektal, gastrointestinal vb.) tedavisinde kullanılan bir kemoterapi ajanıdır. Ancak, plazma yarı ömrünün kısa olması, kanser hücrelerine karşı düşük seçiciliği ve ciddi yan etkilere sebep olması klinik kullanımını sınırlandırmıştır. Bu çalışmada 5-FU’nun kontrollü salım teknolojisi ile olumsuz özelliklerinin en aza indirilmesi hedeflendi. Bu amaçla 5-FU yüklü poli (vinil alkol)/sodyum aljinat (PVA/NaAlg) küreleri FeCl3 kullanılarak iyonik çapraz bağlanma yöntemiyle hazırlandı ve Fourier transform infrared spektroskopi (FTIR), taramalı elektron mikroskopi (SEM) ve diferansiyel taramalı kalorimetri (DSC) ile karakterize edildi. İn vitro salım çalışmaları 2’şer saat süre ile 3 farklı pH (1.2, 6.8 ve 7.4) değerinde toplam 6 saat olacak şekilde gerçekleştirildi. PVA/NaAlg (m/m) oranı, ilaç/polimer (m/m) oranı, çapraz bağlama süresi ve çapraz bağlayıcı derişiminin 5-FU salımı üzerine etkisi araştırıldı. Kürelerde PVA miktarının artmasıyla 5-FU salımının arttığı buna karşın çapraz bağlama süresinin ve çapraz bağlayıcı derişimin artmasıyla 5-FU salımının azaldığı belirlendi.

Anahtar Kelimeler

5-Fluorourasil, Antikanser İlaç, Kontrollü Salım, pH Duyarlı Salım

Controlled Release of 5-Fluorouracil from Biocompatible Polymeric Beads

Öz

5-Fluorouracil (5-FU), a pyrimidine analog, is a chemotherapy agent used in the treatment of a wide variety of cancers (breast, colorectal, gastrointestinal, etc.). However, its short plasma half-life, low selectivity against cancer cells and serious side effects limited its clinical use. In this study, it was aimed to minimize the negative properties of 5-FU with controlled release technology. For this purpose, 5-FU loaded poly(vinyl alcohol)/sodium alginate (PVA/NaAlg) beads were prepared by ionic crosslinking method using FeCl3 and beads were characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and differential scanning calorimetry (DSC). In vitro release studies were carried out for 2 hours at 3 different pH values (1.2, 6.8 and 7.4) for a total of 6 hours. The effects of PVA/NaAlg (w/w) ratio, drug/polymer (w/w) ratio, crosslinking time and crosslinker concentration on 5-FU release were investigated. It was determined that 5-FU release increased with increasing PVA amount in the beads, whereas 5-FU release decreased with increasing crosslinking time and crosslinker concentration.

Anahtar Kelimeler

5-Fluorouracil, Anticancer Drug, Controlled Drug Release, pH Responsive Release

Kaynakça

• A.AL-Kahtani, A, Sherigara, BS, 2014. Semi-interpenetrating network of acrylamide grafted-sodium alginate microspheres for controlled release of diclofenac sodium, preparation and characterization. Colloids and Surfaces B: Biointerfaces, 115, 132–138.
• Agarwal, T, Gautham Hari Narayana, SN, Pal, K, Pramanik, K, Giri, S, Banerjee, I, 2015. Calcium alginate-carboxymethyl cellulose beads for colon-targeted drug delivery. International Journal of Biological Macromolecules, 75, 409-417.
• Arafat, M, Prestidge, CA, Fouladian, P, Wignall, A, Song, Y, Parikh, A, Albrecht, H, Garg, S, Blencowe A, 2021. Development and In Vitro Evaluation of 5-Fluorouracil-Eluting Stents for the Treatment of Colorectal Cancer and Cancer-Related Obstruction. Pharmaceutics, 13, 17.
• Babu, VR, Sairam, M, Hosamani, KM, Aminabhavi, TM, 2007. Preparation of sodium alginate–methylcellulose blend microspheres for controlled release of nifedipine. Carbohydrate Polymers, 69, 241-250.
• Bulut, E, Şanlı O, 2013. Delivery of Alzheimer's Drug Donepezil Hydrochloride from Ionically Crosslinked Alginate Microspheres Prepared by Water-in-oil Emulsion Technique: Optimization of Release Conditions. Asian Journal of Chemistry, 25, 3993-4000.
• Bulut, E, Şanlı, O, 2016. Novel ionically crosslinked acrylamide-grafted poly(vinyl alcohol)/sodium alginate/sodium carboxymethyl cellulose pH-sensitive microspheres for delivery of Alzheimer’s drug donepezil hydrochloride: Preparation and optimization of release conditions. Artificial Cells, Nanomedicine, and Biotechnology, 44(2), 431-442.
• Cutrim, ESM, Vale, AAM, Manzani, D, Barud, HS, Rodriguez-Castellon, E, Santos, APSA, Alcantra, ACS, 2021. Preparation, characterization and in vitro anticancer performance of nanoconjugate based on carbon quantum dots and 5-fluorouracil. Materials Science & Engineering C, 120, 111781.
• Dai, YN, Li, P, Zhang, JP, Wang, AQ, Wei, Q, 2008. “Swelling Characteristics and Drug Delivery Properties of Nifedipine-Loaded pH Sensitive Alginate–Chitosan Hydrogel Beads. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 86, 493-500.
• Dev, A, Mohan, JC, Sreeja, V, Tamura, H, Patzke, GR, Hussain, F, Weyeneth, S, Nair, SV, Jayakumar, R, 2010. Novel carboxymethyl chitin nanoparticles for cancer drug delivery applications. Carbohydrate Polymers, 79, 1073-1079.
• He, T, Wang, W, Chen, B, Wang, J, Liang, Q, Chen, B, 2020. 5-Fluorouracil monodispersed chitosan microspheres: microfluidic chip fabrication with crosslinking, characterization, drug release and anticancer activity, Carbohydrate Polymers, 236, 116094.
• Işıklan, N, 2006. Controlled Release of Insecticide Carbaryl from Sodium Alginate, Sodium Alginate/Gelatin, and Sodium Alginate/ Sodium Carboxymethyl Cellulose Blend Beads Crosslinked with Glutaraldehyde, Journal of Applied Polymer Science, 99, 1310-1319.
• Lin, CC, Fu, CH, 2009. Controlled release study of 5-fluorouracil-loaded chitosan/polyethylene glycol microparticles. Drug Delivery 16, 274-279.
• Olukman, M, Şanlı, O, Kondolot Solak, E, 2012. Release of anticancer drug 5-fluorouacil from different ionically crosslinked alginate beads. Journal of Biomaterials and Nanobiotechnology, 3, 469-479.
• Rama Subba Reddy, P, Eswaramma, S, Krishna Rao, KSV, Ill Lee, Y, 2014. Dual responsive pectin hydrogels and their silver nanocomposites: swelling studies, controlled drug delivery and antimicrobial applications. Bulletin of Korean Chemical Society, 35, 2391-2399.
• Ramesh Babu, V, Hosamani, KM, Aminabhavi TM, 2008. Preparation and in-vitro release of chlorothiazide novel pH-sensitive chitosan-N,N-dimethylacrylamide semi-interpenetrating network microspheres, Carbohydrate Polymers, 71, 208–217.
• Soppirnath, KS, Aminabhavi, TM, 2002. Water transport and drug release study from cross-linked polyacrylamide grafted guar gum hydrogel microspheres for the controlled release application. European Journal of Pharmaceutics and Biopharmaceutics, 53, 87–98.
• Swamy, BY, Yun, YS, 2015. In vitro release of metformin from iron (III) cross-linked alginate-carboxymethyl cellulose hydrogel beads. International Journal of Biological Macromolecules, 77, 114-119.
• Şanlı, O, Ay, N, Işıklan, N, 2007. Release characteristics of diclofenac sodium from poly(vinyl alcohol)/sodium alginate and poly(vinyl alcohol)-grafted- poly(acrylamide)/sodium alginate blend beads. European Journal of Pharmaceutics and Biopharmaceutics, 65, 204-214.
• Şanlı, O, Olukman, M, 2014. Preparation of ferric ion crosslinked acrylamide grafted poly (vinyl alcohol)/sodium alginate microspheres and application in controlled release of anticancer drug 5-fluorouracil. Drug Delivery, 21(3), 213-220.
• Şanlı, O, Kahraman, A, Kondolot Solak, E, Olukman, M, 2016. Preparation of magnetite-chitosan/methylcellulose nanospheres by entrapment and adsorption techniques for targeting the anti-cancer drug 5-fluorouracil. Artificial Cells, Nanomedicine, and Biotechnology, 44, 950-959.
• World Health Organization, 2019. World Health Organization Model List of Essential Medicines, 21st List ed., Geneva, Switzerland.
• Yerri Swamy, B, Venkata Prasad, C, Reddy, CLN, Sudhakara, P, Chung, I, Subha, MCS, Chowdoji Rao, K, 2012. Preparation of Sodium Alginate/Poly(vinyl alcohol) BlendMicrospheres for Controlled Release Applications. Journal of Applied Polymer Science 125, 555–561.
• Zeng, W, Hui, H, Liu, Z, Chang, Z, Wang, M, He, B, Hao, D, 2021. TPP ionically cross-linked chitosan/PLGA microspheres for the delivery of NGF for peripheral nerve system repair. Carbohydrate Polymers, 258, 117684.