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Review
. 2014 Jun;11(6):901-15.
doi: 10.1517/17425247.2014.902047.

Therapeutic applications of hydrogels in oral drug delivery

Lindsey A Sharpe  1 , Adam M Daily, Sarena D Horava, Nicholas A Peppas
Affiliations
Review

Therapeutic applications of hydrogels in oral drug delivery

Lindsey A Sharpe et al. Expert Opin Drug Deliv. 2014 Jun.

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.

Keywords: controlled release; drug delivery; hydrogel; intelligent system; oral delivery.

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Conflict of interest statement

Declaration of interest

This work is supported by a grant from the National Institutes of Health (5-R01-EB-000246-20) and the Fletcher S. Pratt Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Figures

Figure 1
Figure 1
Representation of drug levels in the blood with traditional repeated dosing (solid line) and controlled delivery dosing (dashed line).
Figure 2
Figure 2. The complex physiology of the gastrointestinal tract poses challenges for oral delivery but can be exploited to achieve controlled drug release
Complexation hydrogels can deliver a therapeutic through the harsh environment of the stomach, protecting it from denaturation by acidic pH or digestive enzymes. Drug is released in the upper small intestine, which has a lower population of enzymes, neutral pH and a large surface area accounting for 95% of nutrient absorption, due to decomplexation and an increase in mesh size triggered by ionic repulsion and swelling of the polymer at a high pH. The colon is another commonly targeted site due to neutral pH and lower enzymatic activity. Adapted with permission from [4].
Figure 3
Figure 3. Representation of in vitro release of insulin from P(MAA-g-EG) microparticles in simulated gastric conditions (pH 1.2) and intestinal conditions (pH 6.8)
The formulations vary in ratios of MAA:PEG where (■) is 4:1, (●) is 1:1 and (○) is pure PMAA. Reproduced with permission from [70].
Figure 4
Figure 4. Typical Transwell® transport study setup and experimental data is shown
(A) Diagram of a Caco-2 monolayer grown onto a Transwell system to study the transport of therapeutics. The drug is delivered apically and samples are collected from the basolateral chamber. (B) Typical data from an experiment aiming to increase protein transport across the epithelium are presented. Insulin (●) is transported less effectively than insulin in the presence of P(MAA-g-EG) microparticles (■), whereas insulin conjugated to transferrin (▲) outperformed both due to transferrin receptor-mediated transcytosis. Reproduced with permission from [130]. P(MAA-g-EG): Poly(methacrylic acid) grafted with poly(ethylene glycol).
See this image and copyright information in PMC

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