Assessment of poly(methacrylic acid‐<i>co</i>‐<i>N</i>‐vinyl pyrrolidone) as a carrier for the oral delivery of therapeutic proteins using Caco‐2 and HT29‐MTX cell lines

Carr, Daniel A.; Peppas, Nicholas A.

doi:10.1002/jbm.a.32395

Cited by 38 publications

(24 citation statements)

References 28 publications

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“…High insulin loading efficiencies were observed and the release profile (shown in Fig. 2) shows no insulin release at low pH and complete insulin release within 10 min after exposure to neutral pH [86]. Also promising is the fact that the P(MAA-co-NVP) hydrogel microparticles appear to have no cytotoxic effect on two model cell lines, Caco-2 colon adenocarcinoma cells and HT29-MTX mucus-secreting goblet cells [86].…”

Section: Ph-responsive Hydrogelsmentioning

confidence: 99%

Stimulus-responsive hydrogels: Theory, modern advances, and applications

Koetting

Peters

Steichen

et al. 2015

Materials Science and Engineering: R: Reports

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923

688

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Over the past century, hydrogels have emerged as effective materials for an immense variety of applications. The unique network structure of hydrogels enables very high levels of hydrophilicity and biocompatibility, while at the same time exhibiting the soft physical properties associated with living tissue, making them ideal biomaterials. Stimulus-responsive hydrogels have been especially impactful, allowing for unprecedented levels of control over material properties in response to external cues. This enhanced control has enabled groundbreaking advances in healthcare, allowing for more effective treatment of a vast array of diseases and improved approaches for tissue engineering and wound healing. In this extensive review, we identify and discuss the multitude of response modalities that have been developed, including temperature, pH, chemical, light, electro, and shear-sensitive hydrogels. We discuss the theoretical analysis of hydrogel properties and the mechanisms used to create these responses, highlighting both the pioneering and most recent work in all of these fields. Finally, we review the many current and proposed applications of these hydrogels in medicine and industry.

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Section: Ph-responsive Hydrogelsmentioning

confidence: 99%

Stimulus-responsive hydrogels: Theory, modern advances, and applications

Koetting

Peters

Steichen

et al. 2015

Materials Science and Engineering: R: Reports

Self Cite

923

688

View full text Add to dashboard Cite

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“…Studies seeking to overcome these delivery barriers using pH-responsive hydrogels such as poly(methacrylic acid-grafted-poly(ethylene glycol)) (P(MAA- g -EG)) or poly(methacrylic acid- co -N-vinylpyrrolidone) (P(MAA- co -NVP) to deliver proteins such as insulin and human growth hormone have been relatively successful, but still suffer from low bioavailability compared to injection, resulting in wasted drug and therefore higher cost (Lowman et al, 1999; Carr et al, 2010; Carr and Peppas, 2010; Foss and Peppas, 2004; Kamei et al, 2009; Kavimandan et al, 2006). Additionally, studies seeking to deliver proteins exhibiting high isoelectric points (pI) have been hampered by coulombic interactions in the small intestine between the anionic hydrogel and cationic protein, resulting in binding rather than release for uptake into the bloodstream (Carr et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

pH-Responsive poly(itaconic acid-co-N-vinylpyrrolidone) hydrogels with reduced ionic strength loading solutions offer improved oral delivery potential for high isoelectric point-exhibiting therapeutic proteins

Koetting

Peppas

2014

International Journal of Pharmaceutics

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pH-Responsive hydrogels comprised of itaconic acid copolymerized with N-vinylpyrrolidone (P(IA-co-NVP)) were synthesized and tested as carriers for the oral delivery of high isoelectric point (pI) exhibiting therapeutic proteins. Swelling studies show that P(IA-co-NVP) hydrogels exhibit significantly greater and faster pH-responsive swelling than previously studied methacrylic acid-based hydrogels, achieving up to 68% greater equilibrium swelling and 10.4 times greater swelling in time-limited experiments. Using salmon calcitonin as a model high pI protein therapeutic, we show that P(IA-co-NVP) hydrogels exhibit significantly greater delivery potential than methacrylic acid-based hydrogels. Additionally, we show that utilizing a lower ionic strength solution during drug loading significantly improves drug delivery potential for high pI therapeutics. By using a 1.5 mM PBS buffer rather than the standard 150 mM PBS buffer during loading, up to 83 times as much calcitonin can be delivered in neutral conditions, with up to a 9.6 fold improvement in percent release. Using P(IA-co-NVP) hydrogel microparticles and a low ionic strength loading solution, up to 48 μg calcitonin/mg hydrogel can be delivered in small intestinal conditions. Based on expected absorption in the small intestine, this is sufficient delivery potential for achieving therapeutic dosage via a single, regularly-sized pill taken daily.

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“…P(MAA-g-EG), P(MAA-g-EG-co-Dextran 6,000), P(MAA-g-EG-co-Dextran 100,000) and P(MAA-dg-EG-Pullulan 75,000) microgels of 90 – 120 μm were loaded with insulin according to published protocol [64]. During the loading process, the initial insulin and final insulin concentration were sampled and measured by aqueous high throughput liquid chromatography (HPLC).…”

Section: Methodsmentioning

confidence: 99%

Advanced molecular design of biopolymers for transmucosal and intracellular delivery of chemotherapeutic agents and biological therapeutics

Liechty

Caldorera‐Moore

Phillips

et al. 2011

Journal of Controlled Release

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Hydrogels have been instrumental in the development of polymeric systems for controlled release of therapeutic agents. These materials are attractive for transmucosal and intracellular drug delivery because of their facile synthesis, inherent biocompatibility, tunable physicochemical properties, and capacity to respond to various physiological stimuli. In this contribution, we outline a multifaceted hydrogel-based approach for expanding the range of therapeutics in oral formulations from classical small-molecule drugs to include proteins, chemotherapeutics, and nucleic acids. Through judicious materials selection and careful design of copolymer composition and molecular architecture, we can engineer systems capable of responding to distinct physiological cues, with tunable physicochemical properties that are optimized to load, protect, and deliver valuable macromolecular payloads to their intended site of action. These hydrogel carriers, including complexation hydrogels, tethered hydrogels, interpenetrating networks, nanoscale hydrogels, and hydrogels with decorated structures are investigated for their ability respond to changes in pH, to load and release insulin and fluorescein, and remain non-toxic to Caco-2 cells. Our results suggest these novel hydrogel networks have great potential for controlled delivery of proteins, chemotherapeutics, and nucleic acids.

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Assessment of poly(methacrylic acid‐co‐N‐vinyl pyrrolidone) as a carrier for the oral delivery of therapeutic proteins using Caco‐2 and HT29‐MTX cell lines

Cited by 38 publications

References 28 publications

Stimulus-responsive hydrogels: Theory, modern advances, and applications

Stimulus-responsive hydrogels: Theory, modern advances, and applications

pH-Responsive poly(itaconic acid-co-N-vinylpyrrolidone) hydrogels with reduced ionic strength loading solutions offer improved oral delivery potential for high isoelectric point-exhibiting therapeutic proteins

Advanced molecular design of biopolymers for transmucosal and intracellular delivery of chemotherapeutic agents and biological therapeutics

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