Therapeutic applications of hydrogels in oral drug delivery

Abstract

Introduction Oral delivery of therapeutics, particularly protein-based pharmaceutics, is of great interest for safe and controlled drug delivery for patients. Hydrogels offer excellent potential as oral therapeutic systems due to inherent biocompatibility, diversity of both natural and synthetic material options and tunable properties. In particular, stimuli-responsive hydrogels exploit physiological changes along the intestinal tract to achieve site-specific, controlled release of protein, peptide and chemotherapeutic molecules for both local and systemic treatment applications. Areas covered This review provides a wide perspective on the therapeutic use of hydrogels in oral delivery systems. General features and advantages of hydrogels are addressed, with more considerable focus on stimuli-responsive systems that respond to pH or enzymatic changes in the gastrointestinal environment to achieve controlled drug release. Specific examples of therapeutics are given. Last, in vitro and in vivo methods to evaluate hydrogel performance are discussed. Expert opinion Hydrogels are excellent candidates for oral drug delivery, due to the number of adaptable parameters that enable controlled delivery of diverse therapeutic molecules. However, further work is required to more accurately simulate physiological conditions and enhance performance, which is important to achieve improved bioavailability and increase commercial interest.

Towards Developing Bioresponsive, Self-Assembled Peptide Materials: Dynamic Morphology and Fractal Nature of Nanostructured Matrices

“…Of the different systems, hydrogels that form nanofiber networks are promising in vivo carriers. Hydrogels offer dynamic and novel applications due to their unique properties, including: swelling with water, housing drugs and ligands, and being made into a multitude of mechanical and morphological configurations that provide multiple means of controlling release [4][5][6][7][8]. However, developing exact and tuneable release mechanisms and morphological features can be extremely complicated, needing additional chemical synthesis involving toxic co-solvents, chemical triggers, or full transplantation to provide a fully formed network in vivo [9].…”

pH-Responsive carriers for oral drug delivery: challenges and opportunities of current platforms

“…Mucoadhesion increases the residence time of the carrier at the site of absorption, which promotes increased bioavailability (Huang et al, 2000). It is important to note that pH-responsive of P(MAA-g-EG) hydrogel systems is designed for targeted release of drugs in the upper small intestine (Sharpe et al, 2014), as well as triggering the PEG tethers to promote mucoadhesion at the target absorption site. P(MAA-g-EG) hydrogel systems have been used for the oral delivery of proteins, including IFN-a (Kamei et al, 2009), calcitonin (Kamei et al, 2009) and insulin (Ichikawa & Peppas, 2003), while modifications are necessary for hydrophobic molecules, such as chemotherapeutics.…”

Transient flows in active porous media

“…1). Responsive hydrogels, i.e., hydrophilic polymers embedded and cross-linked into hydrophilic structures [4], can respond to a broad range of stimuli, e.g., pH [5][6][7][8][9][10][11][12][13], temperature [14,15], individual molecules (chemically driven) [16][17][18][19], shear stress [20][21][22][23][24][25], etc., that trigger a change of material properties. In pHinduced responses, hydrogel swelling and deswelling occurs when polymers are ionized by the dynamically changing environmental pH [5].…”

“…In pHinduced responses, hydrogel swelling and deswelling occurs when polymers are ionized by the dynamically changing environmental pH [5]. Hence, the charge buildup results in an electrostatic force generation within the hydrogel that ultimately leads to absorbance or expulsion of water [6,7]. Other workers have investigated temperature-dependent hydrogels utilizing the critical solubility temperature with applications in drug delivery [14] and tissue engineering [15].…”