Semisynthesis of a Controlled Stimuli-Responsive Alginate Hydrogel

Abstract

Benefits of the use of natural polymers include biodegradability, biocompatibility, natural abundance, and unique physicochemical/biological properties. Native alginate was used to semisynthesize a new class of biomaterial in which the physical properties such as swelling and pore size can be chemically tailored for desired end use. Semisynthetic network alginate polymer (SNAP) was prepared by reaction with glutaraldehyde, forming an acetal-linked network polymer gel with carboxylate moieties preserved as stimuli-responsive sensors. The molecular structure of the hydrogel was confirmed by cross-polarization magic-angle spinning (13)C solid state NMR, and reaction parameters affecting the polymer synthesis, including reactant, catalyst concentrations, and solvent composition, were characterized by gel equilibrium swelling. The acetalization reaction can be thermodynamically controlled, offering fine-tuned control of gel swelling and pore properties. In addition, SNAP demonstrated pronounced swelling at alkaline pH and contraction in acidic environment with oscillatory response to repeated pH-stimuli, yielding a potential pulsatile, oral drug delivery vehicle. Through selection of reaction conditions, gel swelling, pore size, and stimuli-responsive characteristics can be specifically tailored for applications such as a tissue scaffold in regenerative medicine, as a targeted delivery vehicle, and as a superabsorbent in environmental cleanup.

Modeling the controllable pH-responsive swelling and pore size of networked alginate based biomaterials

“…Alginate, a linear polysaccharide consisting of anionic block copolymer of b-D-mannuronic acid (M) and a-L-guluronic acid (G) residues, can form physical gels by cooperative binding with divalent cations such as calcium, or form chemical gels by reacting the hydroxyl functional groups with a di-aldehyde via acid-catalyzed acetalization [1,2], with an epoxide via base-catalyzed ring-opening polymerization [3], or by an amine reaction targeting the carboxylic acid functional site, forming imide or amide bond linkages [4,5]. Semisynthetic network alginate polymer (SNAP) hydrogel formed by reaction of hydroxyl functional sites with glutaraldehyde, is stable in ionic media containing chelating agents or monovalent ions such EDTA, citrates, sodium and potassium.…”

“…In contrast, calcium alginate hydrogels are unstable under these conditions. In addition, SNAP hydrogel is pH-responsive, swelling in alkaline and contracting in acid solutions, exhibiting oscillatory swelling/ contraction response under alternating pH step change between 1.2 and 7.8 [2]. SNAP hydrogel has potential applications as biosensors, and as encapsulation matrices for wide range molecular sizes of biologicals and as an oral drug delivery vehicle for protein therapeutics such as insulin.…”

A self-regulating antimicrobial model based on the ion-exchange stimuli

“…, leading to an ordered conformational structure called ''egg-box'' array. The property of Alg hydrogels being sensitive to pH and calcium ions showed potential applications in the field of intelligent DDSs [20][21][22][23][24][25][26][27][28]. However, few studies about the controlling release of nano-silver regulated by the intelligent response of Alg have been reported in the field of antimicrobial wound dressing.…”

Drug loading into and drug release from pH‐ and temperature‐responsive cylindrical hydrogels

“…[4][5][6][7][8] Several beneficial characteristics of hydrogels 9,10 allow their use as drug delivery systems for oral, nasal, buccal, rectal, vaginal, ocular, and parenteral routes of administration. 1,5 Polymers from natural, synthetic, or semisynthetic sources can be used for synthesizing hydrogels for delivery of both hydrophilic and hydrophobic drugs, 4,7,[10][11][12][13][14][15][16] with cylindrical and spherical hydrogels being commonly used. 1,5 Drugs are commonly incorporated into hydrogels by physical entrapment, by either placing a preformed hydrogel in a suitable drug solution or letting the hydrogel monomer(s), mixed with drug, an initiator, and, if necessary, a crosslinker, polymerize.…”

“…PNIPAAm hydrogels and their modifications swell after absorbing water below the LCST and shrink upon expelling water above LCST. 3,7,9,12,18,[24][25][26] pH-responsive hydrogels are composed of polymeric backbones with ionic pendant groups. Anionic hydrogels swell at a pH above the pKa of the hydrogel polymer, and the reverse is the case for cationic hydrogels.…”