Kitosan temelli hidrojellerin hazırlanması ve 5-Florourasil salımı davranışlarının incelenmesi

Yıl 2016, Cilt: 18 Sayı: 2, 12 - 24, 21.12.2016

Sema Ekici

Öz

Kitosan (CH), poli(2-akrilamido-2-metilpropansülfonik asit) (pAMPS) ve poliakrilamid
(pAAm) hidrojelleri içeren, üçlü, iç içe geçmiş ağ yapılı hidrojeller (IPNHs) ve sadece
kitosan hidrojelleri sentezlendi ve model ilaç olarak seçilen 5-Florourasil (5-FLU)
biyoetken moleküllerinin denetimli salımı için araştırıldı. IPNHs; çapraz bağlayıcı
olarak seçilen glutaraldehit (GLU) ve N,N’-metilenbisakrilamid (MBA) varlığında
monomerlerin radikalik polimerleşmesi ile hazırlandı. Hidrojellerin spektroskopik
analizleri; Fourier dönüşümlü infrared spektroskopisi ile yapıldı. IPNH’lerin kinetik ve
dinamik şişme çalışmaları 37 ◦
C’de; mide sıvısına (pH=1.1) ve ince bağırsak sıvısına
(pH=7.4) benzetilmiş tampon çözeltilerde gastrointestinal ilaç salımı çalışmaları için in
vitro olarak araştırıldı. Şişme ve ilaç salım deneysel verileri; şişme ve salım
proseslerinin ikinci dereceden kinetiğe uyduğunu gösterdi. Tutuklanan biyoetken
türlerin IPNH’lerden ve kitosan hidrojellerinden salımının; hidrojel bileşimi ve ortamın
pH’sına bağlı olduğu anlaşıldı. Sonuç olarak; kitosan temelli IPNH’lerin; oral
gastrointestinal salım sistemlerindeki formülasyonlar için ümit verici adaylar
olabileceği söylenebilir. 

Anahtar Kelimeler

Hidrojel, kitosan, akıllı jeller, denetimli salım, 5-Florourasil

Preparation of the hydrogels based chitosan and investigation of release behaviours of 5-Fluorouracil

Öz

Ternary interpenetrating polymeric networks hydrogels (IPNHs) containing chitosan
(CH), poly(2-acrylamido-2-methylpropanesulfonic acid) (PAMPS) and polyacrylamide (pAAm) polymers and bare chitosan hydrogels were synthesized and investigated for
controlled release of bioactive molecules utilizing a model drug, 5-Fluorouracil (5-
FLU). IPNHs were prepared by radical polymerization of monomers in presence of
glutaraldehyde (GLU) and N,N’-methylenebisacrylamide (MBA) selected as
crosslinkers. Spectroscopic analyses of these hydrogels were made with Fourier
transform infrared spectroscopy. Kinetic and dynamic swelling studies of IPNHs were
carried out in buffer solutions simulated gastric fluid (pH=1.1) and simulated intestinal
fluid (pH=7.4) at 37 ◦
C for studies of gastrointestinal drug delivery as in vitro. The
experimental data of swelling and drug release studies suggest clearly that the swelling
and release processes obey second-order kinetics. It was realized that the release of the
entrapped bioactive species from IPNHs and chitosan hydrogels depends on the
composition of the hydrogel and pH of the medium. As a result, it can be said that
IPNHs based chitosan could be promising candidates for formulations in oral
gastrointestinal delivery systems

Anahtar Kelimeler

Hydrogel, chitosan, intelligent gels, controlled release, 5-Fluorouracil

Kaynakça

• Koetting, M. C., Peters, J. T., Steichen, S. D. and Peppas, N. A., Stimulusresponsive hydrogels: Theory, modern advances, and applications, Materials Science and Engineering: R: Reports, 93, 1-49, (2015).
• Ullah, F., Othman, M. B. H., Javed, F., Ahmad, Z. and Akil, H. M., Classification, processing and application of hydrogels: A review, Materials Science and Engineering: C, 57, 1, 414-433, (2015).
• Caló, E. and Khutoryanskiy, V.V., Biomedical applications of hydrogels: A review of patents and commercial products, European Polymer Journal, 65, 252-267, (2015).
• Ozay, H. and Ozay, O.,Rhodamine based reusable and colorimetric naked-eye hydrogel sensors for Fe3+ ion, Chemical Engineering Journal, 232, 364-371, (2013).
• El-Aassar, M. R., El Fawal, G. F., Kamoun, E. A. and Fouda, M. M. G., Controlled drug release from cross-linked κ-carrageenan/hyaluronic acid membranes, International Journal of Biological Macromolecules, 77, 322-329, (2015).
• Lee, J. H. and Yeo, Y., Controlled drug release from pharmaceutical nanocarriers, Chemical Engineering Science, 125, 24, 75-84, (2015).
• Weiser, J. R. and Saltzman, W. M., Controlled release for local delivery of drugs: barriers and models, Journal of Controlled Release,190, 28, 664-673, (2014).
• Kyddonieus, A.F., Fundamental concepts of controlled release, CRC Press, vol I., Florida, US., (1980).
• Hu, X., Wei, W. and Qi, X., Preparation and characterization of a novel pHsensitive Salecan-g-poly(acrylicacid) hydrogel for controlled release of doxorubicin, Journal of Materials Chemistry B, 3, 13, 2685-2697, (2015).
• Zhu, Q. and Li, Z., Hydrogel-supported nano sized hydrous manganese dioxide: Synthesis, characterization, and adsorption behavior study for Pb2+, Cu2+, Cd2+ and Ni2+ removal from water, Chemical Engineering Journal, 281, 69-80, (2015).
• Utkarsh, B., Anindita, L., Kishalay, M. and Saptarshi, M., Sodium alginate and gelatin hydrogels: Viscosity effect on hydrophobic drug release, Materials Letters, 164, 76–79, (2016).
• Kim, M. K., Sundaram, K. S., Iyengar, G. A. and Lee, K., A novel chitosan functional gel included with multiwall carbon nano tube and substituted polyaniline as adsorbent for efficient removal of chromiumion, Chemical Engineering Journal, 267, 51-64, (2015).
• Kandile, N. G., Mohamed, H .M. and Mohamed, M. I., New heterocycle modified chitosan adsorbent for metal ions (II) removal from aqueous systems, International Journal of Biological Macromolecules, 72, 110-116, (2015).
• Gerola, A.P., Silva, D.C., and Jesus, S., Synthesis and controlled curcumin supramolecular complex release from pH-sensitive modified gum-arabic-based hydrogels, RSC Advances, 5, 115, 94519-94533, (2015).
• Wang, J., and Li, J., One-pot synthesis of IPN hydrogels with enhancedmechanical strength for synergistic adsorption of basicdyes, Soft Materials ¸13, 3, 160-166, (2015).
• Ozbas, Z., and Gurdag, G., Swelling kinetics, mechanical properties, and release characteristics of chitosan-based semi-IPN hydrogels, Journal of Applied Polymer Science, 132, 16, 41886, (2015).
• Lohani, A., Singh, G., Bhattacharya, S. S., Hegde, R. R. and Verma, A., Tailored-interpenetrating polymer network beads of κ-carrageenan and sodium carboxymethyl cellulose for controlled drug delivery, Journal of Drug Delivery Science and Technology, 31, 53-64, (2016).
• Wang, J. and He, R., Formation and evaluation of interpenetrating networks of anion exchange membranes based on quaternized chitosan and copolymer poly(acrylamide)/polystyrene, Solid State Ionics, 78, 1, 49-57, (2015).
• Munoz-Pinto, D. J., Jimenez-Vergara, A. C., Gharat, T. P. and Hahn, M. S., Characterization of sequential collagen-poly(ethylene glycol) diacrylate interpenetrating networks and initial assessment of their potential for vascular tissue engineering, Biomaterials, 40, 32-42, (2015).
• Fu, Z., He, C., Li, H., Yan, C., Chen, L., Huang, J. and Liu, Y., A novel hydrophilic–hydrophobic magnetic interpenetrating polymer networks (IPNs) and its adsorption towards salicylic acid from aqueous solution, Chemical Engineering Journal, 279, 1, 250-259, (2015).
• Peppas, N. A., Zach, H. J., Khademhosseini, A. and Langer, R., Hydrogels in biology and medicine: from molecular principles to bionanotechnology, Advanced Materials, 18, 1345–1360, (2006).
• Pairatwachapun, S., Paradee, N. and Sirivat, A., Controlled release of acetylsalicylic acid from polythiophene/carrageenan hydrogel via electrical stimulation, Carbohydrate Polymers, 137, 214–221, (2016).
• Peppas, N. A. and Ritger, P. L., A simple equation for description of solute release I. Fickian and Non-Fickian from non-swellable devices in the from of slabs, spheres, cylinders or dics, Journal of Controlled Release, 5, 23-26, (1987).
• Bajpai, A. K., Bajpai, J. and Shukla, S., Water sorption through a semiinterpenetrating polymer network (IPN) with hydrophilic and hydrophobic chains, Reactive and Functional Polymers, 50, 9-21, (2001).
• Frish, H.L., Sorption and transport in glassy polymers, Polymer Engineering and Science, 20, 2-13, (1980).
• Peppas, N. A. and Franson, N. M., The swelling interface number as a criterion for prediction of diffusional solute release mechanisms in swellable polymers, Journal of Polymer Science, 21, 983–997, (1983).
• Koizhaiganova, R. B., Kudaibergenov, S. E. and Geckeler, K. E., A novel class of betaine-type polyampholytes with stimuli-responsive and complexing properties, Macromolecular Rapid Communications, 23, 1041-1044, (2002).
• Mohan, Y. M. and Geckeler, K. E., Polyampholytic hydrogels: Poly(Nisopropylacrylamide)-based stimuli-responsive networks with poly(ethyleneimine), Reactive and Functional Polymers, 67, 144–155, (2007).
• Ekici, S., Intelligent poly(N-isopropylacrylamide)-carboxymethyl cellulose full interpenetrating polymeric networks for protein adsorption studies, Journal of Materials Science, 46, 2843–2850, (2011).
• Lorenzo, C. A. and Concheiro, A., Reversible adsorption by a pH- and temperature-sensitive acrylic hydrogel, Journal of Controlled Release, 80, 247-257, (2002).
• Shamim, N., Hong, L., Hidajat, K. and Udin, M. S., Thermosensitive-polymercoated magnetic nanoparticles: Adsorption and desorption of bovine serum albümin, Journal of Colloid and Interface Science, 304, 1-6, (2006).
• Brazel, C. S. and Peppas, N. A., Mechanism of solute and drug transport in relaxing, swellable, hydrophilic glassy polymers, Polymer, 40, 3383–3398, (1999).
• Khan, H., Shukla, R. N. and Bajpai, A. K., Genipin-modified gelatin nanocarriers as swelling controlled drug delivery system for in vitro release of cytarabine, Materials Science and Engineering: C, 61, 1, 457-465, (2016).
• Zhang, X. and Cresswell, M., Inorganic controlled release technology, 30, Butterworth-Heinemann Press, Elsevier Ltd., (2016).