Highly porous cellulose beads (CBs) of various mean sizes were successfully prepared from regenerated cellulose of paper wastes. The drug delivery characteristics of CBs with different mean sizes were investigated using curcumin as the model drug under controlled conditions. The loading capacity and efficiency of curcumin onto CBs were substantially influenced by factors such as their morphological characteristics, curcumin concentration, and duration of loading. The release kinetic profiles of curcumin from CBs of different mean sizes were investigated in media of pH values resembling digestive juices and intestinal fluids. Release kinetic models were used to simulate and elucidate release kinetics and mechanisms of curcumin from CBs under specific conditions. The loading capacity and efficiency of curcumin onto CBs could be enhanced via the optimization of curcumin solution concentration and the morphological characteristics of CBs, whereas the release kinetic profiles of curcumin from CBs could be modulated by varying the mean diameter of CBs. Optimized CBs derived from regenerated cellulose of paper wastes are potentially useful as cost-effective drug delivery carriers.
In recent years, porous cellulose beads (CBs) derived from regenerated cellulose are receiving intense research interest for their potential biomedical and biotechnological applications such as chromatography system [
In the pharmaceutical field, CBs constitute the main component in the formulation of drug pellets using the extrusion-spheronization method [
In our previous study, we had reported a green chemistry approach for the fabrication of porous CBs from regenerated cellulose of paper wastes using nonderivatizing and environmental friendly ionic liquid as the reaction medium, and water as the antisolvent [
Printed paper waste was used as the source of cellulose fibres. 1-Allyl-3-methylimidazolium chloride (AMIMCl), sodium dihydrogen phosphate (NaH2PO4), and disodium hydrogen phosphate (Na2HPO4) were purchased from Sigma Aldrich, whereas hydrochloric acid (HCl), sodium hydroxide (NaOH), curcumin, and sodium dodecyl sulfate (SDS) were purchased from Merck. Phosphate buffer saline solution (PBS) was prepared from 1.0 M sodium dihydrogen phosphate (NaH2PO4) and 1.0 M disodium hydrogen phosphate (Na2HPO4) solutions. All chemicals were used without further purification. Ultrapure water (~18.2 MΩ·cm, 25°C) was obtained from the Water Purifying System (ELGA, Model Ultra Genetic).
50.0 g of ground paper wastes was treated with NaOH solution (12.0 wt%) for 24 h at room temperature in order to swell cellulose fibres, as well as to remove residual ink particles and hemicelluloses. Pretreated cellulose fibres were then immersed in HCl solution (1.0 M) at 80°C for 2 h to remove lignin residuals. Purified cellulose fibres were obtained by washing thoroughly with deionized water and then dried until constant weight in an oven at 60°C [
CBs were prepared based on the method reported in our previous paper [
The surface and bulk morphology of as prepared and curcumin-loaded beads were characterized by using scanning electron microscope (JEOL JSM-6390 LA) at accelerating voltages of 5–10 kV. The mean mass and diameter of CBs were determined by measuring mass and diameter of at least 100 individual cellulose beads using an electronic balance and a microgauge, respectively. Specific surface areas (
Curcumin was loaded onto CBs using the absorption method as reported by Athira and Jyothi [
The in vitro curcumin release from CBs was studied in media of different pH values simulating digestive juices (phosphate buffer, pH = 1.23) and intestinal fluids (phosphate buffer, pH = 6.40). 50 mg CBs of different mean sizes were added to 50 mL of phosphate buffer saline (PBS) solution containing 8 g/L of sodium dodecyl sulfate (SDS) at
The release of curcumin from CBs was further analyzed by fitting experimental data to various kinetic models [
In addition, curcumin release kinetics data were fitted to selected empirical kinetic models including the Higuchi, Hixson-Crowell, and Korsmeyer-Peppas models as shown by [
CBs of three different mean diameters were prepared from regenerated cellulose derived from printed paper wastes. Droplets of cellulose solution were extruded from syringe needle nozzles of varying diameter through incorporated gravity force and constant applied pressure. The mean sizes of droplets extruded were varied and controlled based on the diameter of syringe needle nozzle used. CBs were formed from droplets of cellulose solution as they were being extruded into a coagulation bath of ultrapure water. The formation of CBs could be regulated by relative diffusion rates of ultrapure water and cellulose solution into the gelling zone [
All CBs fabricated were observed to possess specific surface area which varied within the range of 101–478 m2/g depending on their mean diameters (Table
Physical properties CPD-dried porous cellulose beads CBs of different mean diameters.
Size code | Mean diameter (mm) | Specific surface area |
Porosity (%) |
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S1 |
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478 | 90.4 |
S2 |
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305 | 88.9 |
S3 |
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101 | 87.3 |
Pore size distribution (a) and (b) swelling ratio of cellulose beads with different diameter ranges.
As prepared dried CBs were of regular spherical shape and white in color (Figure
Schematic representation of curcumin loaded onto cellulose beads.
Porous cellulose beads (CBs) of different mean sizes derived from printed paper wastes: (a) As prepared; S1, S2, and S3 (left to right), (b) curcumin-loaded CBs; S1, S2, and S3 (left to right); SEM micrographs of cross sectional view for (c) as prepared CBs (S1), and (d) curcumin-loaded CBs (S1).
The effect of curcumin concentration on the loading capacity and associated loading efficiency of curcumin for CPD-dried CBs (S2) was shown in Figure
The effect of curcumin solution concentration on the loading capacity and loading efficiency of curcumin for CPD-dried CBs (S2).
The morphological effects of CBs on their loading capacity of curcumin were investigated using CBs prepared by different drying techniques: CPD-, air-, and oven-dried CBs. Figures
SEM micrographs of CBs prepared using different drying techniques (a) CPD-dried, (b) air-dried at room temperature, (c) oven-dried at 60°C, and (d) BET specific surface areas of CBs prepared using different drying techniques.
Figure
The loading capacity and efficiency of curcumin for CBs (S3) as prepared (in water swollen state), and prepared using different drying techniques.
In the case of as prepared water swollen CBs, comparatively higher loading and loading efficiency (0.47 mg/g; 61%) than both of air- and oven-dried CBs were observed. This could be attributed to diffusion driven processes which occurred continuously until an equilibrium state was established between curcumin solution and adsorbed water within the CBs.
The effect of mean bead diameter on the loading capacity of curcumin was investigated for CBs of three different mean diameters (Table
Effect of bead size on the loading capacity of curcumin for CPD-dried CBs with mean diameter of CBs (S1 =
The loading of curcumin onto CBs was conducted by dispersing a known amount of CBs in a given volume of ethanolic curcumin solution of known concentration upon incubation at room temperature and in darkness for various predetermined durations. Figure
Effect of incubation duration on the curcumin loading of CBs (a) UV-Vis spectra of curcumin, (b) loading capacity of curcumin-loaded CBs.
As shown in Figure
The release kinetics of curcumin from CBs of different mean sizes was investigated in media of pH 1.23 and pH 6.40 as simulated digestive juices and intestinal fluids, respectively (Figure
Release kinetic profiles of curcumin for CBs with different mean sizes in PBS solution at (a) pH 1.23 and (b) pH 6.40.
The release kinetics and mechanisms of curcumin for CBs of different mean sizes were further evaluated by fitting to both zero and first-order kinetic equations, as well as various empirical kinetics models, namely, the Hixson-Crowell, Higuchi, and Korsmeyer-Peppas models. All kinetic parameters for the release of curcumin from CBs of different mean sizes and at different media pH values are presented in Table
Released kinetics parameters for curcumin from CBs in media of different pH values.
Kinetic model | Bead size | Medium pH | |||||
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pH = 1.2 | pH = 6.4 | ||||||
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Zero order | S1 | 0.8134 | 5.3761 | 0.9478 | 7.0722 | ||
S2 | 0.9561 | 5.0045 | 0.9684 | 5.6761 | |||
S3 | 0.9722 | 4.3256 | 0.9740 | 5.1764 | |||
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First Oder | S1 | 0.9769 |
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0.9662 |
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S2 | 0.9950 |
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0.9966 |
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S3 | 0.9934 |
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0.9979 | 0.0404 | |||
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Higuchi | S1 | 0.9274 | 22.795 | 0.9958 | 27.470 | ||
S2 | 0.9983 | 20.307 | 0.9993 | 22.897 | |||
S3 | 0.9987 | 17.410 | 0.9994 | 20.823 | |||
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Hixson and Crowell | S1 | 0.7613 |
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0.8987 |
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S2 | 0.9064 |
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0.9098 |
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S3 | 0.9159 |
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0.9129 |
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Korsmeyer- |
S1 | 0.9716 | 0.31 | 1.7008 | 0.9990 | 0.35 | 1.6659 |
S2 | 0.9992 | 0.38 | 1.4834 | 0.9988 | 0.45 | 1.4205 | |
S3 | 0.9989 | 0.50 | 1.2331 | 0.9989 | 0.51 | 1.3093 |
The release kinetics of curcumin for CBs was observed to conform better to the first-order kinetic equation without prominent effects by both bead mean size and medium pH value. CBs of different mean sizes exhibited regression coefficient values of 0.99, indicating that the rate of curcumin release from CBs was mainly dependent upon the total loading of curcumin within CBs. The release of drug molecules from a polymeric substrate could be controlled though three important mechanisms which included swelling followed by diffusion, erosion, and diffusion [
Highly porous cellulose beads of different mean sizes were prepared from regenerated cellulose of paper wastes via a facile and green process. These cellulose beads were subsequently loaded with a model drug, curcumin, under specific experimental conditions. The loading capacity and loading efficiency of curcumin for CBs were prominently affected by their morphological characteristics, notably porosity, specific surface area, and mean diameter. CPD-dried CBs exhibited the highest loading capacity of curcumin at 0.86 mg/g with a loading efficiency exceeding 80%. The release kinetic profiles of curcumin for CPD-dried CBs were substantially affected by the bead mean diameter, and to a lesser extent the pH of releasing medium. Fitting of empirical kinetic models had led to the elucidation of a Fickian diffusion controlled process as the main underlying release mechanisms of curcumin for CPD-dried CBs. The loading capacity and efficiency of curcumin for CBs could be modulated and enhanced via the optimization of curcumin solution concentration and the morphological characteristics of CBs, whereas the release kinetic profiles of curcumin could be modulated by varying the mean diameter of CBs. The potential utility of optimized CBs as cost-effective drug deliver carriers derived from regenerated cellulose via facile and green processes is therefore envisaged.
The authors declare that they have no conflicts of interest.
The authors wish to acknowledge the financial support rendered by the Ministry of Higher Education, Malaysia, via the award of fundamental research grants (Grant nos. FRGS/ST01(01)/967/2013(08) and F07/FRGS/1495/2016), as well as research management and support services provided by the Research Innovation and Management Center (RIMC), Universiti Malaysia Sarawak. The authors also wish to acknowledge Professor Dr. Colin L. Raston, School of Chemical and Physical Sciences, Flinders University, Australia, for his suggestions and comments on the manuscript.