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5-FU Drug Loading During the Production of Hydroxyapatite-Gelatin and Hydroxyapatite-Chitosan Biocomposites in the Simulated Body Fluid Medium and Drug Release Studies

Year 2018, Volume: 11 Issue: 3, 587 - 605, 30.12.2018
https://doi.org/10.18185/erzifbed.413332

Abstract

Hydroxyapatite, (HAp,Ca10(PO4)6(OH)2) is a bioceramic applied in different biomedical areas. In
recent studies, it has been concluded that hydroxyapatite nanoparticles has
inhibition effect on different kind of tumors. Therefore, HAp or composite
materials including HAp have been preferred in controlled drug delivery studies
as a drug carrier. However, hard structure and highly fragile structure
of hydroxyapatite limited its usage in clinical applications. This mechanical
disadvantages can be overcomed by using a polymer to produce a
hydroxyapatite-polymer biocomposite.In this study, hydroxyapatite-gelatin
(HAp-GEL) and hydroxyapatite-chitosan (HAp-CTS) biocomposites were produced by
wet precipitation method at pH 7.4 and 37°C implementing glutaraldehyde (GA) as a
cross-linking agent in the SBF (Simulated Body Fluid) medium. Drug loading
process was performed during the production of biocomposites by wet
precipitation method. By running experiments with different amounts (2% and 5%)
of glutaraldehyde (GA) and different biocomposites, the effect of
glutaraldehyde and type of composite on drug loading efficiency and drug
release profiles were investigated. All experiments were performed with
5-Fluorouracil (5-FU) drug. Drug loading performance of 5-FU at the HAp-GEL and
Hap-CTS biocomposites were determined in deionized water, phosphate buffer
solution (PBS) and HCl solution. To determine of drug loading and drug release
performace of the samples, UV spectrophotometer was used. Fourier transform
infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron
microscopy (SEM),
thermogravimetric analysis (TGA) and particle size analyses were performed to
characterize the produced biocomposites.

References

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Hidroksiapatit-Jelatin ve Hidroksiapatit-Kitosan Biyokompozitlerin Yapay Vücut Sıvısı Ortamında Üretimi Sırasında 5-FU İlacının Yüklenmesi ve İlaç Salım Çalışmaları

Year 2018, Volume: 11 Issue: 3, 587 - 605, 30.12.2018
https://doi.org/10.18185/erzifbed.413332

Abstract

Hidroksiapatit,
(HAp,
Ca10(PO4)6(OH)2) farklı medikal alanlarda uygulaması olan bir
biyoseramiktir. Son yapılan çalışmalarda,
nanoboyutlu HAp parçacıklarının farklı tümör türleri üzerinde gelişimi önleyici
etki gösterdiği görülmüştür. Bu nedenle, HAp veya HAp içeren kompozit
malzemeler kontrollü ilaç salımı uygulamalarında ilaç taşıyıcı ortam olarak
tercih edilmiştir. Ancak, sert yapısı ve yüksek kırılganlığı klinik
uygulamalarda kullanımını sınırlamaktadır. Bu mekanik dezavantajlar, polimer
kullanılarak hidroksiapatit-polimer biyokompozit üretilmesiyle aşılabilmektedir.Bu
çalışmada,
hidroksiapatit-jelatin
(HAp-GEL) ve hidroksiapatit-kitosan (HAp-CTS) biyokompozitler, pH 7.4 ve 37°C’
de yaş çöktürme yöntemiyle, çapraz bağlama ajanı olarak gluteraldehitin (GA)
kullanıldığı SBF (Yapay Vücut Sıvısı) ortamında üretilmiştir. İlaç yüklemi
işlemi, biyokompozitlerin yaş çöktürme yöntemi ile üretimi sırasında
gerçekleştirilmiştir. Farklı miktarlarda (%2 ve %5) gluteraldehit (GA) ve
farklı biyokompozitler ile yürütülen deneylerde gluteraldehitin ve biyokompozit
türünün ilaç yükleme verimi ve ilaç salım profili üzerine etkisi incelenmiştir.
Tüm deneyler 5-Fluorouracil (5-FU) ilacı ile gerçekleştirilmiştir. HAp-GEL ve
Hap-CTS biyokompozitlerde 5-FU ilacının yüklenme performansı deiyonize su,
fosfat tampon çözelti (PBS) ve HCl çözelti ortamında incelenmiştir. Numunelerin
5-FU ilaç yükleme ve ilaç salımı performansının belirlenmesinde UV
spektrofotometre kullanılmıştır. Üretilen biyokompozitleri karakterize etmek
için, Fourier dönüşümlü kızılötesi spektroskopi (FTIR), X-ışını kırınımı (XRD),
taramalı elektron mikroskobu (SEM), termogravimetrik analiz (TGA) ve partikül
boyut analizleri yapılmıştır.

References

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  • Arami, H., Mohajerani, M., Mazloumia, M., Khalifehzadeh, R., Laka, A. Sadrnezhaad, S.K. 2008. Rapid Formation of Hydroxyapatite Nanostrips Via Microwave Irradiation. Journal of Alloys and Compounds, 469, 391–394.
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  • Başargan, T., Erdol Aydin, N., Nasun-Saygılı, G. 2017. Hydroxyapatite-chitosan Biocomposites Synthesized in the Simulated Body Fluid and Their Drug Loading Studies. Journal of Material Science: Materials in Medicine, 28, 180 (10).
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  • Elhassan, G.O. 2017. Design and Evaluation of Controlled Release Matrix Tablet of Aspirin by Using Hydrophobic Polymer. International Journal of Pharmaceutical Research and Allied Sciences, 6(4), 32-41.
  • El-Tahlawy, K.F., El-bendary, M.A., Elhendawy, A.G., Hudson, S.M. 2005. The Antimicrobial Activity of Cotton Fabrics Treated with Different Crosslinking Agents and Chitosan. Carbohydrate Polymers, 60, 421-430.
  • Fomin, A.S., Barinov, S., Ievlev, V.M., Smirnov, V.V., Mikhailov, B.P., Belonogov, E.K., Drozdova, N.A. 2008. Nanocrystalline Hydroxyapatite Ceramics Produced by Low-Temperature Sintering After High-pressure Treatment. Chemical Technology, 418 (3), 352–355.
  • Fournier, E., Passirani, C., Colin,N., Breton, P., Sagodira, S., Benoit, J. 2004. Development of Novel 5-FU-loaded Poly(methylidene malonate 2.1.2)-based Microspheres for the Treatment of Brain Cancers. European Journal of Pharmaceutics and Biopharmaceutics, 57, 189–197.
  • Ganguly, K., Aminabhavi, T.M., Kulkarni, A.R. 2011. Colon targeting of 5-Fluorouracil Using Polyethylene Glycol Cross-linked chitosan Microspheres Enteric Coated with Cellulose Acetate Phthalate, Industrial & Engineering Chemistry Research, 50, 11797–11807.
  • Gomez-Guillen, M.C., Gimenez, B., Caballero, M., Montero, M.P. 2011. Functional and Bioactive Properties of Collagen and Gelatin from Alternative Sources: A Review, Biochemical Journal, 25(8), 1813-1827.
  • Gouda, R., Baishya, H., Qing, Zhao 2017. Application of Mathematical Models in Drug Release Kinetics of Carbidopa and Levodopa ER Tablets. Journal of Developing Drugs, 6(2).
  • Guang, W.Y. 2002. The effect of Chitosan and Its Derivatives on the Dyeability of Silk. Ph.D. Thesis, Hong Kong Polytechnic University. Hasret, E. 2010. Hidroksiapatit Sentezi, Karakterizasyonu ve Adsorban Özelliğinin İncelenmesi. Yüksek Lisans Tezi, İTÜ Fen Bilimleri Enstitüsü, İstanbul, 10-22.
  • Hench, L. 1991.Bioceramics from Concept to Clinic. Journal of the American Ceramic Society, 74 (7), 1487-1510.
  • Jain, A., Jain, S.K. 2016. In vitro release kinetics model fitting of liposomes: An insight. Chemistry and Physics of Lipids, 201, 28-40.
  • Janes, K.A., Calvo, P., Alonso, M.J. 2001. Polysaccharide Colloidal Particles as Delivery Systems for Macromoleculs. Advanced Drug Delivery Reviews, 47, 83- 97.
  • Kahraman, E. 2017. SBF Ortamında Üretilen Hidroksiapatit-Jelatin Kompozit Malzemelerin İlaç Salım Performansının İncelenmesi, Yüksek Lisans Tezi, İTÜ-Fen Bilimleri Enstitüsü, İstanbul.
  • Kalita, S.J., Bhardwaja, A. 2007. Nanocrystalline Calcium Phosphate Ceramics in Biomedical Enginering. Material Science Engineeering: C, 27(3), 441-449.
  • Kim, H.W., Knowles, J.C., Kim, H.E. 2005. Porous Scaffolds of Gelatin-Hydroxyapatite Nanocomposites Obtained by biomimetic approach: Characterization and Antibiotic Drug Release. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 74 (2) 686-698.
  • Kumar, S., Koh, J. 2012. Physiochemical, Optical and Biological Activity of Chitosan-Chromone Derivative for Biomedical Applications. International Journal of Molecular Sciences, 13, 6102-6116.
  • Kumari, S., Rath, P., Kumar, A.S.H., Tiwari, T.N. 2015. Extraction and characterization of chitin and chitosan from fishery waste by chemical method. Environmental Technology & Innovation, 3, 77-85.
  • Li, Y., Liu, T., Zheng, J., Xu, X. 2013. Glutaraldehyde-crosslinked Chitosan/hydroxyapatite Bone Repair Scaffold and Its Application as Drug Carrier for Icariin. Journal of Applied Polymer Science, 130 (3), 1539-1547.
  • Lin, Y., Li, Y., Ooi, C.P. 2012. 5-Fluorouracil Encapsulated HA/PLGA Composite Microspheres for Cancer Therapy. Journal of Materials Science: Materials in Medicine, 23, 2453–2460.
  • Liu, Y., Hou, D., Wang, G., 2004. A Simple Wet Chemical Synthesis and Characterization of Hydroxyapatite Nanorods. Materials Chemistry and Physics, 86, 69–73.
  • Lopez-Macipe, A., Rodriguez-Clemente, R., Hidalgo-Lopez, A., Arita, I., Garcia-Garduno, M.V., Rivera, E. ve Castano, V.M. 1998. Wet Chemical Synthesis of Hydroxyapatite Particles from Nonstoichiometric Solutions. Journal of Materials Synthesis and Processing, 6(1), 21-26.
  • Misra, A., Shahiwala, A. 2014. Applications of Polymers in Drug Delivery, Smithers Rapra, US, Ch.2, 1-38.
  • Mobasherpour, I., Soulati Heshajin, M., Kazemzadeh, A., Zakeri, M. 2007. Synthesis of Nanocrystalline Hydroxyapatite by Using Precipitation Method. Journal of Alloys and Compounds, 430(1-2), 330–333.
  • Murugan R. ve Ramakrishna, S.2005. Development of Nanocomposites for Bone Grafting. Composites Science and Technology, 65, 2385-2406.
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There are 58 citations in total.

Details

Primary Language Turkish
Subjects Engineering
Journal Section Makaleler
Authors

Nalan Erdöl Aydın

Publication Date December 30, 2018
Published in Issue Year 2018 Volume: 11 Issue: 3

Cite

APA Erdöl Aydın, N. (2018). Hidroksiapatit-Jelatin ve Hidroksiapatit-Kitosan Biyokompozitlerin Yapay Vücut Sıvısı Ortamında Üretimi Sırasında 5-FU İlacının Yüklenmesi ve İlaç Salım Çalışmaları. Erzincan University Journal of Science and Technology, 11(3), 587-605. https://doi.org/10.18185/erzifbed.413332