PREPARATION, CHARACTERISATION AND EVALUATION OF HYDROXYAPATITE-SODIUM ALGINATE NANOCOMPOSITES FOR APPLICATION IN ANTICANCER DRUG DELIVERY
PREPARATION, CHARACTERISATION AND EVALUATION OF HYDROXYAPATITE-SODIUM ALGINATE NANOCOMPOSITES FOR APPLICATION IN ANTICANCER DRUG DELIVERY
No Thumbnail Available
Date
2016-12
Authors
ONOYIMA, Christian Chinweuba
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
Chemotherapy is one of the leading means of treating cancer. However, the side effects and complications arising from the dose-dependent toxicity of anticancer drugs are often as severe as the disease itself. This research was aimed at preparation and characterization of nanocomposites from hydroxyapatite (HA) and sodium alginate (SA), and evaluation of their applications in controlled delivery of doxorubicin (DOX) and methotrexate (MTX). In situ preparation of hydroxyapatite-sodium alginate (HASA) nanocomposite was carried out by the wet precipitation methods. The prepared HA and the nanocomposite were characterized by Fourier Transform Infrared spectroscopy (FTIR), Scanning Electron Microscopy (SEM), X-Ray Fluorescence (XRF) and X-Ray Diffraction (XRD) analyses. Drug loading was carried out at neutral pH, while in vitro drug release study was carried out in synthetic body fluid (SBF) at pH 7.4 and 37oC. Four different loading methods were investigated. Method 1 involved adsorbing the drug in already prepared nanocomposites. In method 2, the dried HA was cross-linked with SA in the drug solution using calcium chloride solution; in method 3 the hydroxyapatite was first incubated in the drug solution before the cross-linking stage; while in method 4 the freshly prepared hydroxyapatite was cross-linked with sodium alginate in the drug solution. The effect of pH of the release medium on release profile was studied using pH 3.0, pH 5.0 and pH 7.4; and drug combination study was also carried out. FTIR study showed peaks that confirmed the formation of HA as well as the formation of the composite. Image analysis revealed that the HA and the nanocomposites were of nanometre size (24.67 nm – 997.09 nm) with irregular morphologies as shown by the circularity (0.119 – 0.988) and aspect ratio (0.149 – 1). The particle size decreased with increase in SA composition from 359.46 nm for HASA-1%wt to 109.98 nm for HASA-50%wt. A similar trend was observed for crystallite size (28.39 nm – 9.47 nm) and degree of crystallinity (49.29% - 1.82%), while circularity and aspect ratio did not show any noticeable change with SA addition. XRD analysis showed the apatite phase to be composed of pure HA and carbonate-HA. Both phases were responsible for the major peaks at 2𝜃 = 25.880 (d-value = 3.4394 Å), 31.770 (d-value = 2.8144 Å), and 32.150 (d-value = 2.7818 Å), which were assigned Miller indices of (002), (121), and (112) planes, respectively. These planes were also present in all the HASA samples. There was no notable effect on the peak positions with the addition of SA. The result of drug loading study showed that the nanocomposites have high loading efficiency for DOX, which increased with increase in SA composition reaching a
vii
maximum value of 92.03% for HASA-50%wt, while for MTX the loading efficiency was relatively low and decreased with increase in SA composition with the highest loading efficiency of 35.24% for pure hydroxyapatite. There was sustained release of DOX by the nanocomposites with SA composition of 5%wt and above for about 57 hours, while MTX showed short release time for all the formulations with maximum release time of 5 hours for HASA-5%wt. Except for HA and HASA-1%wt, the DOX release followed first order release kinetics, with Fickian diffusion as the predominant release mechanism. Nanocomposite prepared in aqueous medium had higher loading efficiency (83.69%) compared with those prepared in organic solvents (52.46%, 47.50%, and 46.50%). The release profiles also showed that nanocomposites from aqueous medium had least burst release effect and more sustained release. The release kinetics and mechanism however, did not depend on the synthetic medium. DOX was loaded well (above 80% loading efficiency) by all the four loading methods studied, while for MTX, method 2 and 4 had better loading efficiency (39.98% and 37.10% respectively) than method 1 and 3 (10.39% and 15.21% respectively). Release study for DOX, indicated that the adsorption method had faster release rate than other methods; while for MTX, only method 4 sustained the release of the drug for about 9 hours, while other methods had high burst release effects. DOX release rate was initially faster at acidic conditions than at physiologic condition, but became slower at later release times. From the drug combination study, the release profiles for all the combination ratios showed high burst release for MTX with total release time not exceeding five hours. However for DOX, there was sustained release throughout the thirty three hours of the study. In conclusion, HASA nanocomposite was successfully prepared and characterised. Its ability to load and release the drugs depended on the nature of the drug as well as the synthetic medium and the loading method employed. The nanocomposite if prepared under optimal conditions is a potential carrier for effective delivery of DOX.
Description
A THESIS SUBMITTED TO THE SCHOOL OF POSTGRADUATE STUDIES,
AHMDU BELLO UNIVERSITY, ZARIA
IN PARTIAL FULFILMENT OF THE REQUIREMENT FOR THE AWARD
OF A
Ph. D. DEGREE IN ANALYTICAL CHEMISTRY
DEPARTMENT OF CHEMISTRY,
FACULTY OF PHYSICAL SCIENCE,
AHMADU BELLO UNIVERSITY, ZARIA
NIGERIA
DECEMBER,
Keywords
PREPARATION,, CHARACTERISATION,, EVALUATION,, HYDROXYAPATITE-SODIUM ALGINATE NANOCOMPOSITES,, APPLICATION,, ANTICANCER DRUG DELIVERY,