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

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.

Keywords

• Biocomposite,Hydroxyapatite,Drug Release,Drug Loading,Gelatin,Chitosan

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

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.

Keywords

• Hidroksiapatit,Biyokompozit,İlaç Salım,İlaç Yükleme,Jelatin,Kitosan

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