Engineering Strategies for Oral Therapeutic Enzymes to Enhance Their Stability and Activity

  • Philipp Lapuhs
  • Gregor FuhrmannEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1148)


Oral application of therapeutic enzymes is a promising and non-invasive administration that improves patient compliance. However, the gastrointestinal tract poses several challenges to the oral delivery of proteins, including harsh pH conditions and digestive proteases. A promising way to stabilise enzymes during their gastrointestinal route is by modification with polymers that can provide both steric shielding and selective interaction in different digestive compartments. We give an overview of modification technologies for oral enzymes ranging from functionalisation of native proteins, to site-specific mutation and protein-polymer engineering. We specifically focus on enzymes that are active directly in the gastrointestinal lumen and not systemically absorbed. In addition, we discuss examples of microparticle and nanoparticle encapsulated enzymes for improved oral delivery. The modification of orally administered enzymes offers a broad chemical variability and may be a promising tool for enhancing their gastrointestinal stability.


Exogenous enzymes Gastrointestinal tract Oral delivery Enzyme therapy Protein-polymer conjugates Non-invasive imaging Gastro-resistant coating Pharmaceutical formulation Stomach-resistant coatings 



2-bromoisobutyryl bromide


Alkaline phosphatase


Atom transfer radical polymerization


Bicinchoninic acid


Benzoyl-l-tyrosine p-nitroanilide


Cellulose acetate phthalate


Circular dichroism


Confocal laser scanning microscopy






Dynamic light scattering


Differential scanning calorimetry


1-ethyl-3-(3-dimethyl-aminopropyl) carbodiimide


Food and drug administration USA


Fluorescein isothiocyanate conjugate - bovine serum albumin


Fourier-transform infrared spectroscopy




Gel permeation chromatography




Hyaluronic acid




High performance liquid chromatography


Hydroxyl propyl methyl cellulose phthalate


Horseradish peroxidase


Liquid chromatography–mass spectrometry


Lower critical solution temperature


Matrix assisted laser desorption ionization time-of-flight mass spectrometry




Branched PEG N-hydroxysuccinimide


Molecular weight


Nanoceramic cores






Nuclear magnetic resonance








Polymer-based protein engineering


Poly (carboxybetaine acrylamide)


Poly(2-(dimethylamino)ethyl methacrylate)


Poly[N,N′-dimethyl (methacryloylethyl) ammonium propane sulfonate]


Polyethylene glycol


Proline-specific endopeptidase


Poly (N-isopropylacry-lamide)


Poly(oligoethylene glycol monomethylether methacry-late)


Poly-(quarternary ammonium methacrylate


Poly-(sulfonate methac-rylate)


Room temperature


Sodium dodecyl sulfate–polyacrylamide gel electrophoresis


Size exclusion chromatography


Scanning electron microscopy


Simulated gastric conditions


Simulated gastric fluid


Simulated intestinal tract conditions


Simulated intestinal fluid




Transmission electron microscopy


Denaturation midpoint


Triple mutant-Anabaena variabilis phenylalanine ammonia lyase


2,4,6-trinitrobenzene sulfonic acid


Upper critical solution temperature


Ultraviolet-visible α1-anti




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Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Biogenic Nanotherapeutics Group (BION)SaarbrückenGermany
  2. 2.Department of PharmacySaarland UniversitySaarbrückenGermany

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