Controlled rheology and drug release of natural polymer-based complex biofluids

Abstract

Natural polymer-based complex fluids have gained a great deal of attention because they have biocompatibility, biodegradability, and sustainability. In addition, natural polymer chains, such as hyaluronic acid and cellulose fibrils, form 3 dimensional networks in aqueous media, thus showing viscoelastic properties. They exhibit mechanical response to external stress or strain, which stems from reversible inter-chain interactions. Thanks to these features, they have high potentials for applications in the biomedical, pharmaceutical and cosmetic fields. For successful application, the rheological property of complex fluids should be controlled depending on the purpose. In this study, the effective techniques to control the viscoelastic properties of natural polymer solution were developed using tunable physical interaction including electrostatic attraction, chain entanglement, and hydrogel bonding. Finally, we demonstrated that the natural polymer with controlled rheological property can be applied to the hydrogel composite for drug delivery system. In chapter 2, we report a facile but straightforward way to control the rheological properties of hyaluronic acid (HA) solutions by taking advantage of the interchain association of electrostatically attractive polymeric micelles (APMs). For this, we synthesized an amphiphilic triblock copolymer, poly(2-aminoethyl methacrylate)-block-poly(3-caprolactone)-block-poly(2-aminoethyl methacrylate) (PAMA-b-PCL-b-PAMA), via atomic transfer radical polymerization and co-assembled it with amphiphilic poly(ethylene oxide)-block-poly(ε-caprolactone) (PEO-b-PCL) to produce APMs with cationic charges. The incorporation of the APMs into a gel-type HA solution not only readily transitioned the viscous flow to elastic flow but also easily led to the deformation of the gel microstructure in response to the shear rate, which is comparable to the case of a linear HA solution. We identified that the unique rheological behavior of the gel-type HA solutions stemmed from the APM-mediated particulate crosslinking. Finally, we demonstrated that the fine tuning of the interchain association by manipulation of the electrostatic interactions between APMs and HA molecules enabled the diversification of the rheological properties of HA solutions, making this system a promising hydrogel rheology controller. In chapter 3, we propose a hydrogel composite that has high mechanical stability and ability to apply for on-demand drug delivery system, in which polyacrylamide (PAM) based hydrogel is reinforced with bacterial cellulose nanofibers (BCNFs) using semi-IPN technique. The physical properties of PAM/BCNF hybrid hydrogel are characterized by controlling the aspect ratio of BCNFs. The hybrid hydrogel containing BCNF with larger aspect ratio showed 4.3-fold higher in elastic modulus compared with that fabricated with PAM only. It is determined that this reinforcement stemmed from inter-fibrillary interaction between PAM and BCNF chains. Water swelling kinetic studies suggested that the chain-chain interactions within hydrogel led to the formation of strong gel phase, which was controllable by BCNF aspect ratio-dependent manner. From further study on drug release, we have confirmed that hybrid hydrogel can not only remarkably retard drug releasing, but also enable on-demand drug release in response to an external mechanical stimulation.