Novel biopolymer applications as adsorbent, drug encapsulation and controlled drug release agents

Abstract

Biopolymers are polymers derived from biological sources. Biopolymers can be subdivided into plant-derived polysaccharides and animal-derived proteins. Firstly, cellulose and then chitin as a polysaccharide are among the most well-known biopolymers thanks to their high abundance, wide distribution on earth and low production costs. The group of proteins mainly includes silk, gelatin, collagen and albumin. Similarly, chitin derivative chitosan, alginate (Alg), gum (gum), carboxymethyl cellulose (CMC) and starch are also included in the category of polysaccharides, and these biopolymers have found numerous applications by using them in various forms. The fact that biopolymers are non-toxic, biodegradable and create composite materials with different additives easily increases their applicability. Considering their sustainability, biocompatibility and mostly hydrophilic properties, biopolymers generally have high advantages over synthetic polymers. Due to their unique properties such as their renewable resources, abundance, biodegradability and ease of functionalization, biopolymers are being investigated for both academic and industrial applications. Water treatment with biopolymers and biopolymer composites is one of the most sought-after research topics today. Reducing the resulting pollutants from wastewater is of vital importance for living organisms. Biopolymer-based adsorbents have the potential to replace traditional adsorbents such as silica, alumina, and activated carbon. They can compete with other adsorbents in terms of adsorption capacity, cost-effectiveness, and biocompatibility. In the first and second steps in this thesis, adsorption studies were carried out to remove harmful substances from the aqueous environment by means of biopolymer-based adsorbents. Different biopolymer-containing materials prepared as adsorbent materials in the physical form of films and beads were used in the removal studies from aqueous media. Biopolymers also have potential applications in the pharmaceutical industry for the development of controlled drug release systems. Biopolymers, with their abundance and natural content, are of great interest as carriers that will realize controlled drug release with the compatibility they will show in the stages of degradation in biological systems. In the ongoing third and fourth steps of this thesis study, drug encapsulation into new biopolymer materials and controlled release of drugs into the desired environment were investigated. In the first stage of the thesis, an anionic surfactant sodium dodecyl benzene sulfonate (SDBS) was chosen as the harmful substance to remove from the aqueous medium. The uncontrolled mixing of surfactants into the environment is an important problem today. Cross-linked chitosan biopolymer films were utilized to the removal of SDBS from the aqueous solution. Sodium sulfate was chosen as the cross-linker. Batch adsorption studies show that the positively charged chitosan has an interaction with the negatively charged surfactant SDBS. In experimental studies, adsorption parameters such as contact time, pH, cross-linker concentration and adsorbent dose were investigated. The maximum amount of adsorbed SDBS was reached at pH 2 and 180 minutes. Experimental data was modeled using kinetic and adsorption isotherm models and it was found that the adsorption system followed pseudo-second-order kinetics and the Langmuir adsorption isotherm model. The adsorption capacity of the films for SDBS adsorption was calculated as 714 mg/g. This study proposes a potential use of cross-linked chitosan films for the removal of anionic surfactants from the aqueous medium. The results of the study have been published in an SCI journal (Journal of Polymers and the Environment, 2018, 26, 2166-2172). In the second stage of the thesis, it was aimed to demonstrate the use of the novel composite material prepared by adding CeO2 nanoparticles to carboxymethyl cellulose (CMC) beads cross-linked with Ce3+ ions as being an efficient adsorbent in fluoride ions removal from water. The characterization of the beads was carried out by swelling experiments, scanning electron microscopy and Fourier transform infrared spectroscopy. The adsorption of fluoride ions from aqueous solutions was carried out with both cerium ions cross-linked CMC beads (CMC-Ce) and CeO2-nanoparticle loaded CMC-Ce beads (CeO2-CMC-Ce) in a batch system. Optimized adsorption conditions were obtained under experimental conditions where parameters such as pH, contact time, adsorbent dose and agitation speed were investigated and a constant temperature value was 25 °C. Experimental data on adsorption showed good agreement with the Langmuir isotherm and pseudo-second-order kinetics. The maximum adsorption capacity of the adsorbents was obtained as 105 and 312 mg F-/g adsorbent for CMC-Ce and CeO2-CMC-Ce beads, respectively. Reusability studies have shown that adsorbent beads exhibit excellent sustainable properties up to 9 cycles. This study revealed that the CeO2 nanoparticle doped CMC-Ce composite is a very effective adsorbent in removing fluoride from water. The results of the study have been published in a SCI journal (International Journal of Biological Macromolecules, 2023, 242(1), 124595). In the third phase of the thesis, it was aimed to reduce the drug release in the acidic stomach environment and to transport the drug to the colon environment with the highest possible encapsulation amount. Protein-type drugs are disrupted at extremely acidic stomach pH. If such drugs reach the intestine without being degraded in the stomach environment, they can be absorbed by the intestinal mucosa. Therefore, research focuses on new approaches for colon-targeted delivery systems. The pH-sensitive properties of some polysaccharides make them colon-targeting agents. One of them is the biopolymer alginate. Alginate (Alg) shrinks in the stomach environment and mostly retains the drug encapsulated in the gel. In the thesis study, the biopolymer alginate was modified with sodium dodecyl sulfate (SDS), an agent whose interaction with protein is known. Bovine serum albumin (BSA) protein selected as the model drug was loaded onto SDS-modified calcium alginate beads (SDS/Ca-Alg). The encapsulation efficiency of BSA in SDS/Ca-Alg beads was found to be 96.3% with a high yield, which can be called complete confinement. The second remarkable result from the experimental studies is that the protein release from the SDS-modified calcium alginate beads into the artificial gastric fluid medium is significantly reduced compared to the protein release from the calcium alginate beads. At the same time, the release time of the entire drug from the SDS/Ca-Alg beads into the artificial intestinal medium was significantly prolonged compared to the Ca-Alg beads. SDS-modified alginate beads are recommended as suitable carriers for the passage of oral protein-type drugs into the colonic environment by preventing their degradation in acidic gastric fluid. The results of the study have been published in an SCI journal (Carbohydrate Polymers, 2019, 224, 115165). In the fourth phase of the thesis, barium alginate-carboxymethyl cellulose composite hydrogel beads were prepared as a controlled release agent that retards the release of the cancer drug methotrexate (MTX) into a phosphate-buffered saline (PBS) medium with a pH value of 7.4. The biggest advantage of alginate as a drug carrier in oral drug applications is its low level of swelling in the acidic gastric fluid environment. Thus, the drug entrapped in the alginate gel and taken orally is largely transported to the intestinal environment. However, in the basic pH environment, uncontrolled and rapid release of the drug is observed with sudden swelling and disintegration of the alginate gel. Recent innovative studies have focused on slowing the swelling rate of alginate in basic medium with suitable additives or forming composites of alginate and other polysaccharides. According to the literature review, this is the first study on MTX release from an alginate-carboxymethyl cellulose matrix into a PBS medium. Ba-Alg/CMC beads to be used in drug release experiments were prepared by adding the solution, which is a mixture of sodium alginate (NaAlg)/sodium carboxymethyl cellulose (NaCMC) biopolymers, into barium chloride solution. As a method in the preparation of the beads, dropping the polymer solution with a syringe into the solution containing barium ions was applied. Since MTX has low water solubility, the drug was first dissolved in DMSO and added to the polymer solution. The amount of DMSO added to the beads to dissolve the drug in the biopolymer solution (10% v/v) positively affected the morphology, swelling and release profiles of the beads. Scanning electron microscopy (SEM) and Fourier-transformed infrared (FTIR) spectroscopy analysis were used to characterize Ba-Alg/CMC composites. The results showed that the release of almost all the amount of MTX loaded on the beads was completed in 5 hours in PBS (pH 7.4 and 37 oC) with a release percentage of 98.1±2.64%. In addition, the synthesized Cu(II) (MXT-Cu) and Zn(II) (MXT-Zn) metal complexes of the drug were also loaded onto Ba-Alg/CMC beads and subjected to drug release studies. The entrapment efficiency of metal complexes of MTX in Ba-Alg-CMC and their release behaviour into PBS were compared with MTX. The data of the controlled release experiments was process to the first-order, Higuchi and Hixson-Crowell kinetic models, which are the most widely used drug release kinetic models. The results of the study have been published in an SCI journal (Journal of Drug Delivery Science and Technology, 2019, 54, 101324). The successive steps of this thesis study were completed in four stages on the applicability of new biopolymer-based materials for adsorption and controlled drug release. The results obtained from the experiments at each stage were presented to the literature as four original research articles published in journals within the scope of SCI in the Q1 (3) and Q2 (1) category. The fact that the materials containing biopolymer, which are successful adsorbent and controlled drug release agents, prepared in line with the outputs of the thesis study, will be beneficial to humanity in the coming years will be a complete indicator of the realization of the purpose. It is foreseen that the thesis will contribute to scientific knowledge through the articles published as a result of the research carried out within the scope of the thesis.