Chemically modified peptides and proteins - critical considerations for oral delivery

Buckley, Stephen T.; Hubálek, František; Rahbek, Ulrik Lytt

doi:10.1080/21688370.2016.1156805

Cited by 36 publications

(15 citation statements)

References 53 publications

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“…Consequently, pharmaceutical and biotechnological companies are conducting numerous studies and testing new techniques to find the ideal modification [97]. Short chains of both chitosan and polyethylene glycol (PEG) represent the most utilized conjugates because they overcome the issue of low solubility and improve the formulation stability in the GIT [102]. Lee et al developed a conjugate of insulin and low molecular weight chitosan (LMWC) in an attempt to enhance the oral delivery of insulin.…”

Section: Protein-polymer Conjugationmentioning

confidence: 99%

Review of recently used techniques and materials to improve the efficiency of orally administered proteins/peptides

et al. 2019

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Objectives The main objective of present review is to explore and evaluate the effectiveness of recently developed methods to improve the bioavailability of orally administered biopharmaceutical drugs. Methods A systematic search of sciencedirect, tandfonline and Google Scholar databases based on various sets of keywords was performed. All results were evaluated based on their abstracts, and irrelevant studies were neglected during further evaluation. Results At present, biopharmaceuticals are used as injectable therapies as they are not absorbed adequately from the different routes of drug administration, particularly the oral one. Their insufficient absorption is attributed to their high molecular weight, degradation by proteolytic enzymes, high hydrophilicity and rigidity of the absorptive tissues. From industrial aspect incorporation of enzyme inhibitors (EIs) and permeation enhancers (PEs) and mucoadhesive polymers into conventional dosage forms may be the easiest way of formulation of orally administered macromolecular drugs, but the effectiveness of protection and absorption enhancement here is the most questionable. Conjugation may be problematic from regulatory aspect. Encapsulation into lipid-based vesicles sufficiently protects the incorporated macromolecule and improves intestinal uptake but have considerable stability issues. In contrast, polymeric nanocarriers may provide good stability but provides lower internalization efficacy in comparison with the lipid-based carriers. Conclusion It can be concluded that the combination of the advantages of mucoadhesive polymeric and lid-based carriers in hybrid lipid/polymer nanoparticles may result in improved absorption and might represent a potential means for the oral administration of therapeutic proteins in the near future.

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Section: Protein-polymer Conjugationmentioning

confidence: 99%

Review of recently used techniques and materials to improve the efficiency of orally administered proteins/peptides

et al. 2019

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“…Chemical modification could provide a more efficient uptake of cargoes across the epithelial barrier of the gastrointestinal tract (Buckley et al, 2016). Chemical modification could provide a more efficient uptake of cargoes across the epithelial barrier of the gastrointestinal tract (Buckley et al, 2016).…”

Section: Structural Modificationmentioning

confidence: 99%

“…Numerous approaches were explored to date for delivery of proteins or peptides through the oral route. Chemical modification could provide a more efficient uptake of cargoes across the epithelial barrier of the gastrointestinal tract (Buckley et al, 2016). Generally, structural modifications of proteins and peptides include prodrug, analogous formation, modification of C-or N-terminals (e.g., polymer conjugation, post-terminal modification, site specific modification), conjugation with fatty acids (e.g., irreversible lipidization, reversible lipidization), combination of both site-specific modification and lipidization, hydrophobic ion pairing, complexation with cyclodextrins, and current technologies (e.g., Nobex technology, Emisphere technology) (Mahajan et al, 2014).…”

Section: Structural Modificationmentioning

confidence: 99%

Improvements in chemical carriers of proteins and peptides

Bolhassani

2019

Cell Biology International

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The successful intracellular delivery of biologically active proteins and peptides plays an important role for therapeutic applications. Indeed, protein/peptide delivery could overcome some problems of gene therapy, for example, controlling the expression levels and the integration of transgene into the host cell genome. Thus, protein/peptide drug delivery showed a promising and safe approach for treatment of cancer and infectious diseases. Due to the unique physical and chemical properties of proteins, their production (e.g., isolation, purification & formulation) and delivery represented significant challenges in pharmaceutical studies. Modification in the structural moieties of these protein/peptide drugs could improve their solubility, stability, crystallinity, lipophilicity, enzymatic susceptibility and targetability, and subsequently, therapies and cures against various diseases. Using the structural modification of protein/peptide, their delivery provided overall higher success rates including high specificity, high activity, bioreactivity and safety. Recently, biotechnological and pharmaceutical companies have tried to find novel techniques for the modifications and improve delivery systems/carriers. However, each carrier has its own benefits and drawbacks, and an appropriate carrier is often established by the physicochemical properties of protein or peptide, the ideal route of injection, and clinical characteristics of therapy. In this review, an attempt was made to give an overview on the chemical carriers for proteins and peptides as well as the recent advances in this field.

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“…Furthermore, due to its role in the treatment of diabetes and concomitant diseases insulin is perhaps the protein, the chemistry of which has been investigated most intensively. Accordingly, the corresponding literature is vast, and it is impossible to give due attention to seminal contributions about insulin modifications, herein; for some more or less randomly chosen, more general review articles published in the last two decades see references . The goal of investigations of insulin is, of course, to improve its bioavailability and activity profile, and to possibly make it orally available.…”

Section: Introductionmentioning

confidence: 99%

Labeling and Protecting N‐Terminal Protein Positions by β‐Peptidyl Aminopeptidase‐Catalyzed Attachment of β‐Amino‐Acid Residues – Insulin as a First Example

Kolesińska

Waśko

Kamiński

et al. 2018

Helvetica Chimica Acta

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Dedicated to Elias J. Corey on the occasion of his 90th birthdayWe have shown for the first time that a natural protein (human insulin) can be acylated at the N-terminus with a b-amino acid (H-b 3 hAla-), in a process catalyzed by the b-peptidyl aminopeptidase 3-2W4-BapA. This selective modification, which could also be applied for protein labeling and tagging, should be generally useful, also to protect peptides and proteins from attack by common aminopeptidases.

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Chemically modified peptides and proteins - critical considerations for oral delivery

Cited by 36 publications

References 53 publications

Review of recently used techniques and materials to improve the efficiency of orally administered proteins/peptides

Review of recently used techniques and materials to improve the efficiency of orally administered proteins/peptides

Improvements in chemical carriers of proteins and peptides

Labeling and Protecting N‐Terminal Protein Positions by β‐Peptidyl Aminopeptidase‐Catalyzed Attachment of β‐Amino‐Acid Residues – Insulin as a First Example

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