Design, synthesis, characterization and evaluation of Chitosan-based hydrogel for controlled drug delivery system
- Authors: Safari, Justin Bazibuhe
- Date: 2022-04
- Subjects: Chitosan , Drug delivery systems , Drugs Controlled release , Tenofovir , Colloids , Hepatitis B Chemotherapy , Hydrogel
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/232182 , vital:49969
- Description: Hepatitis B infection is a deadly infectious disease caused by the hepatitis B virus and is responsible for many deaths every year worldwide. Despite medication and vaccines against hepatitis B infection, it still presents high morbidity and mortality among populations. This is partly due to factors such as a long medication period of the existing treatments, resulting in poor patient compliance and leading to treatment failure. In addition, this situation can be responsible for the observed emerging drug resistance. Hence, novel drugs and drug delivery systems are needed to tackle this matter. Many strategies have been used to develop long-acting drug delivery systems treatment for several infectious diseases. Hydrogel drug delivery systems have shown interesting results as controlled drug delivery systems for several drugs. Therefore, the present study aimed to develop chitosan grafted poly (acrylamide-co-acrylic acid) hydrogel and apply it as a pH-sensitive controlled delivery system of tenofovir disoproxil fumarate (TDF). TDF is a nucleoside reverse transcriptase inhibitor used as first-line treatment of hepatitis B chronic infection and in the treatment of other viral infections. The free-radical polymerization method was utilized to modify chitosan by grafting acrylamide and acrylic acid and using N, N’-methylene bisacrylamide as the crosslinking agent to prepare the hydrogel, followed by an optimization of parameters that could affect the swelling capacity. The prepared chitosan-g-poly(acrylamide-co-acrylic acid) hydrogel was characterized using Fourier Transmission Infra-red spectroscopy (FTIR), X-Ray Diffraction (XRD), Thermal Gravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC), Energy-dispersive X-ray spectroscopy (EDS), Scanning Electron Microscopy (SEM), and was evaluated for cytotoxicity using a HeLa cell assay. TDF was used as a drug model, it was loaded by the swelling equilibrium method, following by the investigation of the release profile of TDF-loaded hydrogel at pH 1.2 and 7.4. A successful synthesis of chitosan grafted poly(acrylamide-co-acrylic acid) hydrogel was confirmed by Fourier Transmission Infra-red spectroscopy (FTIR), X-Ray Diffraction Spectroscopy (XRD), Thermal Gravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC), Energy-dispersive X-ray spectroscopy (EDS) and Scanning Electron Microscopy (SEM). Optimization results showed that the ratio of monomers impacted the swelling ratio of the hydrogel and both the concentration of the crosslinking agent, and the reaction initiator also affected the swelling ratio. The synthesized hydrogels were sensitive to pH and ionic strength. Hydrogel swelling was lower in acidic solutions and higher in neutral and basic solutions and decreased with the increasing ionic strength. Furthermore, SEM results revealed that hydrogel have a rough and fibrous surface structure with numerous pores. Cytotoxicity studies demonstrated that the hydrogel was non-cytotoxic at 50 μg/ml against HeLa cells which suggested a good biocompatibility of the material. TDF was loaded and released from the hydrogels and showed an encapsulation efficiency and drug loading percentage ranging from 81-96% and 8-10%, respectively. TDF release profile was found to be low in buffer solution of pH 1.2 (in the range of 5-10%) and much higher (38-53%) at pH 7.4 within 96 hours. TDF maintained its chemical integrity after release and the hydrogels can therefore be proposed as a new controlled-release drug delivery system for hepatitis B treatment. , Thesis (MSc) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-04
- Authors: Safari, Justin Bazibuhe
- Date: 2022-04
- Subjects: Chitosan , Drug delivery systems , Drugs Controlled release , Tenofovir , Colloids , Hepatitis B Chemotherapy , Hydrogel
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/232182 , vital:49969
- Description: Hepatitis B infection is a deadly infectious disease caused by the hepatitis B virus and is responsible for many deaths every year worldwide. Despite medication and vaccines against hepatitis B infection, it still presents high morbidity and mortality among populations. This is partly due to factors such as a long medication period of the existing treatments, resulting in poor patient compliance and leading to treatment failure. In addition, this situation can be responsible for the observed emerging drug resistance. Hence, novel drugs and drug delivery systems are needed to tackle this matter. Many strategies have been used to develop long-acting drug delivery systems treatment for several infectious diseases. Hydrogel drug delivery systems have shown interesting results as controlled drug delivery systems for several drugs. Therefore, the present study aimed to develop chitosan grafted poly (acrylamide-co-acrylic acid) hydrogel and apply it as a pH-sensitive controlled delivery system of tenofovir disoproxil fumarate (TDF). TDF is a nucleoside reverse transcriptase inhibitor used as first-line treatment of hepatitis B chronic infection and in the treatment of other viral infections. The free-radical polymerization method was utilized to modify chitosan by grafting acrylamide and acrylic acid and using N, N’-methylene bisacrylamide as the crosslinking agent to prepare the hydrogel, followed by an optimization of parameters that could affect the swelling capacity. The prepared chitosan-g-poly(acrylamide-co-acrylic acid) hydrogel was characterized using Fourier Transmission Infra-red spectroscopy (FTIR), X-Ray Diffraction (XRD), Thermal Gravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC), Energy-dispersive X-ray spectroscopy (EDS), Scanning Electron Microscopy (SEM), and was evaluated for cytotoxicity using a HeLa cell assay. TDF was used as a drug model, it was loaded by the swelling equilibrium method, following by the investigation of the release profile of TDF-loaded hydrogel at pH 1.2 and 7.4. A successful synthesis of chitosan grafted poly(acrylamide-co-acrylic acid) hydrogel was confirmed by Fourier Transmission Infra-red spectroscopy (FTIR), X-Ray Diffraction Spectroscopy (XRD), Thermal Gravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC), Energy-dispersive X-ray spectroscopy (EDS) and Scanning Electron Microscopy (SEM). Optimization results showed that the ratio of monomers impacted the swelling ratio of the hydrogel and both the concentration of the crosslinking agent, and the reaction initiator also affected the swelling ratio. The synthesized hydrogels were sensitive to pH and ionic strength. Hydrogel swelling was lower in acidic solutions and higher in neutral and basic solutions and decreased with the increasing ionic strength. Furthermore, SEM results revealed that hydrogel have a rough and fibrous surface structure with numerous pores. Cytotoxicity studies demonstrated that the hydrogel was non-cytotoxic at 50 μg/ml against HeLa cells which suggested a good biocompatibility of the material. TDF was loaded and released from the hydrogels and showed an encapsulation efficiency and drug loading percentage ranging from 81-96% and 8-10%, respectively. TDF release profile was found to be low in buffer solution of pH 1.2 (in the range of 5-10%) and much higher (38-53%) at pH 7.4 within 96 hours. TDF maintained its chemical integrity after release and the hydrogels can therefore be proposed as a new controlled-release drug delivery system for hepatitis B treatment. , Thesis (MSc) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-04
Optimising the polymer solutions and process parameters in the electrospinning of Chitosan
- Authors: Jacobs, Nokwindla Valencia
- Date: 2012
- Subjects: Textile fibers, Synthetic , Nanofibers , Chitosan , Polymer solutions
- Language: English
- Type: Thesis , Doctoral , DPhil
- Identifier: vital:10449 , http://hdl.handle.net/10948/d1010762 , Textile fibers, Synthetic , Nanofibers , Chitosan , Polymer solutions
- Description: Electrospinning is a technique, which can be used to produce nanofibrous materials by introducing electrostatic fields into the polymer solution. Due to their intrinsic properties, such as small fiber diameter, small pore size and large surface area, nanofibres are suitable for use in a variety of applications including wound dressing, filtration, composites and tissue engineering. The study demonstrates the successful and optimised production of Poly(ethylene oxide) (PEO) and chitosan nanofibres by electrospinning. The biocidal effects of chitosan, chitosan-silver nanofibres and silver nanoparticles were successfully investigated. To set up a functional electrospinning apparatus, the PEO solution parameters (concentration, molecular weight, solvent, and addition of polyelectrolyte) and applied potential voltage on the structural morphology and diameter of PEO nanofibres were studied. At lower PEO concentrations, the fibres had morphology with a large variation in fibre diameter, whereas at the higher concentrations, the nanofibres exhibited ordinary morphology with uniform but larger fibre diameters. Higher molecular weight showed larger average diameters when compared to that obtained with the same polymer but of a lower molecular weight. The addition of polyelectrolyte to the polymer solution had an influence on the structural morphology of the PEO. Flow simulation studies of an electrically charged polymer solution showed that an increase in the flow rate was associated with an increase in poly(allylamine hydrochloride) (PAH) concentration for the low molecular weight polymer, the shape and size of the Taylor cone increasing with an increase in PAH concentration for the low molecular weight polymer. During optimization of the PEO nanofibres, based on statistical modelling and using the Box and Behnken factorial design, the interaction effect between PAH concentration and the tip-to-collector distance played the most significant role in obtaining uniform diameter of nanofibres, followed by the interaction between the tip-to-collector distance and the applied voltage and lastly by the applied voltage. The production and optimization of chitosan nanofibres indicated that the interactions between electric field strength and the ratio of trifluoroacetic acid (TFA) and dichloromethane (DCM), TFA/DCM solvents as well as between electric field strength and chitosan concentration had the most significant effect, followed by the concentration of chitosan in terms of producing nanofibres with uniform diameters. Chitosan and chitosan-silver nanofibres could be successfully electrospun by controlling the solution properties, such as surface tension and electrical conductivity with the silver nanoparticles in the chitosan solutions affecting the electrospinnability. The silver nanoparticles in the chitosan solution modified the morphological characteristics of the electrospun nanofibres, while the conductivity and the surface tension were elevated. The fibre diameter of the chitosan and chitosan-silver nanoparticles decreased with an increase in the silver content. The electrospun chitosan nanofibres had a smooth surface and round shape as compared to the silver-chitosan nanofibres with a distorted morphology. The chitosan and chitosan-silver nanofibres as well as the silver nanoparticles exhibited antimicrobial or inhibition activity against S. aureus than against E. coli. S. aureus bacterial culture showed good cell adhesion and spreading inwards into the chitosan nanofibrous membrane. The chitosan-silver nanofibres exhibited a greater minimum inhibitory concentration (MIC), followed by silver nanoparticles and then chitosan nanofibres; suggesting a synergistic effect between the chitosan and silver nanoparticles.
- Full Text:
- Date Issued: 2012
- Authors: Jacobs, Nokwindla Valencia
- Date: 2012
- Subjects: Textile fibers, Synthetic , Nanofibers , Chitosan , Polymer solutions
- Language: English
- Type: Thesis , Doctoral , DPhil
- Identifier: vital:10449 , http://hdl.handle.net/10948/d1010762 , Textile fibers, Synthetic , Nanofibers , Chitosan , Polymer solutions
- Description: Electrospinning is a technique, which can be used to produce nanofibrous materials by introducing electrostatic fields into the polymer solution. Due to their intrinsic properties, such as small fiber diameter, small pore size and large surface area, nanofibres are suitable for use in a variety of applications including wound dressing, filtration, composites and tissue engineering. The study demonstrates the successful and optimised production of Poly(ethylene oxide) (PEO) and chitosan nanofibres by electrospinning. The biocidal effects of chitosan, chitosan-silver nanofibres and silver nanoparticles were successfully investigated. To set up a functional electrospinning apparatus, the PEO solution parameters (concentration, molecular weight, solvent, and addition of polyelectrolyte) and applied potential voltage on the structural morphology and diameter of PEO nanofibres were studied. At lower PEO concentrations, the fibres had morphology with a large variation in fibre diameter, whereas at the higher concentrations, the nanofibres exhibited ordinary morphology with uniform but larger fibre diameters. Higher molecular weight showed larger average diameters when compared to that obtained with the same polymer but of a lower molecular weight. The addition of polyelectrolyte to the polymer solution had an influence on the structural morphology of the PEO. Flow simulation studies of an electrically charged polymer solution showed that an increase in the flow rate was associated with an increase in poly(allylamine hydrochloride) (PAH) concentration for the low molecular weight polymer, the shape and size of the Taylor cone increasing with an increase in PAH concentration for the low molecular weight polymer. During optimization of the PEO nanofibres, based on statistical modelling and using the Box and Behnken factorial design, the interaction effect between PAH concentration and the tip-to-collector distance played the most significant role in obtaining uniform diameter of nanofibres, followed by the interaction between the tip-to-collector distance and the applied voltage and lastly by the applied voltage. The production and optimization of chitosan nanofibres indicated that the interactions between electric field strength and the ratio of trifluoroacetic acid (TFA) and dichloromethane (DCM), TFA/DCM solvents as well as between electric field strength and chitosan concentration had the most significant effect, followed by the concentration of chitosan in terms of producing nanofibres with uniform diameters. Chitosan and chitosan-silver nanofibres could be successfully electrospun by controlling the solution properties, such as surface tension and electrical conductivity with the silver nanoparticles in the chitosan solutions affecting the electrospinnability. The silver nanoparticles in the chitosan solution modified the morphological characteristics of the electrospun nanofibres, while the conductivity and the surface tension were elevated. The fibre diameter of the chitosan and chitosan-silver nanoparticles decreased with an increase in the silver content. The electrospun chitosan nanofibres had a smooth surface and round shape as compared to the silver-chitosan nanofibres with a distorted morphology. The chitosan and chitosan-silver nanofibres as well as the silver nanoparticles exhibited antimicrobial or inhibition activity against S. aureus than against E. coli. S. aureus bacterial culture showed good cell adhesion and spreading inwards into the chitosan nanofibrous membrane. The chitosan-silver nanofibres exhibited a greater minimum inhibitory concentration (MIC), followed by silver nanoparticles and then chitosan nanofibres; suggesting a synergistic effect between the chitosan and silver nanoparticles.
- Full Text:
- Date Issued: 2012
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