Development of nanocomposite hydrogels for controlled release of proteins

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2016
Sivri, Seda
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Owing to the fact that a vast number of biological functions are performed via proteins in living tissues, many human diseases are resulted from the malfunction or deficiency of particular proteins. Hence, there has been extensive work on industrial production of therapeutic proteins for the treatment of diseases in recent years. However, proteins could be denatured or degraded in vivo in a short time before reaching target site due to their fragile nature. Additionally, owing to the renal clearance and short half-lives of proteins, frequent injection or excessive protein loading is required to reach a therapeutically effective dose in vivo. Therefore, there has been necessity of controlled release systems which effectively deliver proteins in a targeted, controlled manner while preserving their structure and function. In this study, alginate based injectable nanocomposite hydrogels with hydrazone bonds were prepared. Due to the incorporation of Laponite XLG, a synthetic clay, these hydrogels were presumed to have higher drug loading capacity and provide a better control of protein release. vi Adsorption studies were conducted for Bovine Serum Albumin (BSA) and Laponite XLG in the weight ratio ranging from 0.33 to 10 for various pH and molarity values. The maximum adsorption percentage of BSA was found to be 99.2±0.57 % while the highest adsorption capacity was attained as 1.1±0.01 mg BSA for per mg Laponite XLG. BSA-Laponite XLG complexes were evaluated via Fourier Transform Infrared Spectroscopy (FTIR) and X-Ray Diffraction technique (XRD). It was found from FTIR analysis that secondary structure of BSA in the complexes was conserved. The results of XRD analysis showed that BSA molecules formed intercalated structure with Laponite XLG. Alginate based injectable hydrogels were produced with hydrazone chemistry and polymer concentrations ranging from 1.7% to 5.75% (w/v). Stability of hydrazone bond at neutral medium and degradation of hydrogels were investigated via swelling test for pure hydrogels and Laponite XLG containing nanocomposite hydrogels. Hydrogels containing 3.2% (w/v) polymer concentration conserved hydrogel morphology in the period of 3 months and demonstrated a stable swelling profile. Laponite XLG incorporation with 0.1% (w/v) into hydrogels contributed to increased degradation time and a controlled release profile. Protein containing hydrogels were produced with 2.55% (w/v) polymer concentration and 0.2% (w/v) BSA addition. Protein containing nanocomposite hydrogels were generated with 2.55% (w/v) polymer concentration and the addition of BSA-Laponite XLG complexes, in which 59% (w/w) of the protein was in adsorbed to Laponite XLG, with 0.2% (w/v) BSA, 0.2% (w/v) Laponite XLG. Influence of Laponite XLG and adsorption mechanism on release of BSA from hydrogels were evaluated with Bradford Assay. Burst release was minimized via addition of BSA-Laponite XLG complexes. After 3 days, protein entrapped in the hydrogel matrix for protein containing hydrogel. However, release of BSA was continued for protein containing nanocomposite hydrogels. BSA release was comparably higher but more stable in the protein containing nanocomposite hydrogels. 
Colloids., Proteins., Alginates., Nanocomposites (Materials).
http://etd.lib.metu.edu.tr/upload/12620391/index.pdf
https://hdl.handle.net/11511/26093
Graduate School of Natural and Applied Sciences, Thesis

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Citation Formats
S. Sivri, “Development of nanocomposite hydrogels for controlled release of proteins,” M.S. - Master of Science, Middle East Technical University, 2016.
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