ArticleJournal of controlled release : official journal of the Controlled Release Society2016
pH-responsive and enzymatically-responsive hydrogel microparticles for the oral delivery of therapeutic proteins: Effects of protein size, crosslinking density, and hydrogel degradation on protein delivery.
Article in Journal of controlled release : official journal of the Controlled Release Society, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 115 citations in OpenAlex.
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- Recent Developments in Protein-Based Hydrogels for Advanced Drug Delivery Applications.Pharmaceutics · 2026Review
- Hydrogel Network Architecture Design Space: Impact on Mechanical and Viscoelastic Properties.Gels (Basel, Switzerland) · 2025Review
- From Basic to Breakthroughs: The Journey of Microfluidic Devices in Hydrogel Droplet Generation.Gels (Basel, Switzerland) · 2025Review
- New Dawn in the Treatment of Rheumatoid Arthritis: Advanced Insight into Polymer Hydrogel Research.Gels (Basel, Switzerland) · 2025Review
- IgG-Binding Peptidomimetic Mixed-Charge Polymer-Modified Resins for Chromatographic Purification of Antibodies.ACS applied materials & interfaces · 2024Article
- The Current and Promising Oral Delivery Methods for Protein- and Peptide-Based Drugs.International journal of molecular sciences · 2024Review
- A Comprehensive Review of Small Interfering RNAs (siRNAs): Mechanism, Therapeutic Targets, and Delivery Strategies for Cancer Therapy.International journal of nanomedicine · 2023Review
- Redox-Responsive Hydrogels for Tunable and "On-Demand" Release of Biomacromolecules.Bioconjugate chemistry · 2022Article
- Fragmenting Bulk Hydrogels and Processing into Granular Hydrogels for Biomedical Applications.Journal of visualized experiments : JoVE · 2022Article
- Hydrogels and Hydrogel Nanocomposites: Enhancing Healthcare through Human and Environmental Treatment.Advanced healthcare materials · 2022Review
- Current and Future Prospective of Injectable Hydrogels-Design Challenges and Limitations.Pharmaceuticals (Basel, Switzerland) · 2022Review
- One-Step Fabrication of Hollow Spherical Cellulose Beads: Application in pH-Responsive Therapeutic Delivery.ACS applied materials & interfaces · 2022Article
- Enhancement of bioactivity, thermal stability and tumor retention by self-fused concatenation of green fluorescent protein.Biochemistry and biophysics reports · 2021Article
- The therapeutic importance of acid-base balance.Biochemical pharmacology · 2021Review
- Recent Advances in Smart Biomaterials for the Detection and Treatment of Autoimmune Diseases.Advanced functional materials · 2020Article
- Solid Lipid Microparticles for Oral Delivery of Catalase: Focus on the Protein Structural Integrity and Gastric Protection.Molecular pharmaceutics · 2020Article
- Antibody drug separation using thermoresponsive anionic polymer brush modified beads with optimised electrostatic and hydrophobic interactions.Scientific reports · 2020Article
- Micro and nanoscale technologies in oral drug delivery.Advanced drug delivery reviews · 2020Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Two potential platform technologies for the oral delivery of protein therapeutics were synthesized and tested. pH-responsive poly(itaconic acid-co-N-vinyl-2-pyrrolidone) (P(IA-co-NVP)) hydrogel microparticles were tested in vitro with model proteins salmon calcitonin, urokinase, and rituximab to determine the effects of particle size, protein size, and crosslinking density on oral delivery capability. Particle size showed no significant effect on overall delivery potential but did improve percent release of encapsulated protein over the micro-scale particle size range studied. Protein size was shown to have a significant impact on the delivery capability of the P(IA-co-NVP) hydrogel. We show that when using P(IA-co-NVP) hydrogel microparticles with 3 mol% tetra(ethylene glycol) dimethacrylate crosslinker, a small polypeptide (salmon calcitonin) loads and releases up to 45 μg/mg hydrogel while the mid-sized protein urokinase and large monoclonal antibody rituximab load and release only 19 and 24 μg/mg hydrogel, respectively. We further demonstrate that crosslinking density offers a simple method for tuning hydrogel properties to variously sized proteins. Using 5 mol% TEGDMA crosslinker offers optimal performance for the small peptide, salmon calcitonin, whereas lower crosslinking density of 1 mol% offers optimal performance for the much larger protein rituximab. Finally, an enzymatically-degradable hydrogels of P(MAA-co-NVP) crosslinked with the peptide sequence MMRRRKK were synthesized and tested in simulated gastric and intestinal conditions. These hydrogels offer ideal loading and release behavior, showing no degradative release of encapsulated salmon calcitonin in gastric conditions while yielding rapid and complete release of encapsulated protein within 1h in intestinal conditions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.