Hydrogels For Biomedical Applications: From Bio-adhesive to Drug Delivery

Abstract

There is a need for materials to replace the use of sutures and staples in surgical procedures. Amongst all the alternatives, special attention has been paid to hydrogels because of their unique and interesting mechanical and physiochemical properties which can meet the requirements of an ideal wound sealant. Specifically, a wound sealant may attach to tissue by molecular cross-linking or through mechanical interlocking with the underlying tissue. Commercially available adhesive sealants are limited by inadequate adhesion, biocompatibility and degradability. So, it is desired to introduce a novel biodegradable and biocompatible surgical adhesive with high strength and minimal immune or inflammatory response. The first part of this dissertation (Chapter 2 and 3) focuses on the use of novel hydrogels as bio-adhesives. For this purpose, various polymers were employed and characterized with different characterization techniques such as 1H, 13C NMR, GPC, FTIR analysis. In order to increase the adhesion of these materials to the target tissue, a positively charged functional group, guanidinium, was immobilized on to the polymer backbones. The electrostatic interactions of these cationic groups on polymers with negatively charged molecules presenting at the tissue surface and cell membrane might cause strong adhesion. Hydrogels were prepared in-situ, simply by mixing two different polymer solutions without the need for any catalyst or initiator. The mechanical properties of the gels were studied which showed not enough strength of these hydrogels for being used as surgical glues. Some approaches were taken to improve the mechanical properties; however, this area of biomedical application needs more investigation.

Another biomedical application of hydrogels investigated in this study was drug delivery. Controlled drug release enhances the safety and efficiency of drug administration. Using hydrogels as delivery platforms is a new technology which can improve and control the release rate of bioactive compounds. Hydrogels closely resemble living tissues due to their high water content. So, these networks exhibit a reduced risk of toxicity and inflammation which is ideal for a drug carrier. The second part of this thesis (Chapter 4 and 5) describes the ability of hydrogels in sustained/controlled release studies applying two different model drugs. The hydrogels were formed in-situ, with different levels of cross-linking by Schiff-base chemistry, which is a reversible reaction, and could be hydrolysed and result in degradation of the cross-linked matrices. The cross-linking density was the key factor in the characteristics of the gels such as degradation rate, swelling and rheological behaviour. The precursors of the hydrogels were injectable fluids which can be presented into the body in a minimally invasive manner followed by solidification at the target site/tissue. Release of a hydrophilic model drug was studied in Chapter 4, where the drug was dissolved into the precursor solution and then entrapped inside the cross-linked system during the hydrogel formation. However, current polymeric systems (e.g. the gels made in Chapter 4) encounter difficulties with loading hydrophobic molecules into their aqueous networks and the subsequent release of the drug from the gel matrices. Cyclodextrins offer a potential solution to the hydrophobic drug delivery challenge. These supramolecules possess internal hydrophobic cavities which can partially or entirely accommodate hydrophobic molecules. Chapter 5 explores the ability of cyclodextrin-based hydrogels in encapsulation and release of a hydrophobic model drug. The interaction of cyclodextrin-functionalized polymers with the hydrophobic drug was analyzed using 1H NMR, FTIR, DSC and SEM and showed the capacity of these polymers in encapsulation of the model drug.

Overall, different types of cross-linking chemistry were studied in this project to produce hydrogels with potential application in the biomedical area. Some of the hydrogels showed weak mechanical properties and need to be studied in greater detail in order to make a stronger surgical adhesive. Some other hydrogels exhibited good properties which make them interesting materials in drug delivery and the subject of further in vivo studies.