Orally active-targeted drug delivery systems for proteins and peptides

Li, Xiuying; Yu, Miaorong; Fan, Weiwei; Gan, Yong; Hovgaard, Lars; Yang, Mingshi

doi:10.1517/17425247.2014.924500

Cited by 36 publications

(18 citation statements)

References 83 publications

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“…Unlike their small-molecule counterparts, it is not currently viable to deliver the necessary doses of protein pharmaceuticals via oral routes such as capsules and tablets [2,3]. As a result, proteins are almost invariably delivered via liquid injections (intravenous IV, intramuscular IM, or sub-cutaneous SC), although delivery via other routes is an active area of research [4].…”

Section: Introductionmentioning

confidence: 99%

Protein aggregation and its impact on product quality

Roberts

2014

Current Opinion in Biotechnology

256

175

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Protein pharmaceutical products are typically active as folded monomers that are composed of one or more protein chains, such as the heavy and light chains in monoclonal antibodies that are a mainstay of current drug pipelines. There are numerous possible aggregated states for a given protein, some of which are potentially useful, while most of which are considered deleterious from the perspective of pharmaceutical product quality and performance. This review provides an overview of how and why different aggregated states of proteins occur, how this potentially impacts product quality and performance, fundamental approaches to control aggregate formation, and the practical approaches that are currently used in the pharmaceutical industry.

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Section: Introductionmentioning

confidence: 99%

Protein aggregation and its impact on product quality

Roberts

2014

Current Opinion in Biotechnology

256

175

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“…This means that there is an interaction between the targeting ligands on the nanocarrier and the receptors on the cell membranes. This recognition is specific, promoting particle internalization [120,121]. Thus, modifying the surface of nanomaterials with particular ligands is one way to improve their cellular uptake and endosomal escape [39].…”

Section: Functionalized Nanomaterialsmentioning

confidence: 99%

Strategies for the enhanced intracellular delivery of nanomaterials

Azevedo

Macedo

Sarmento

2018

Drug Discovery Today

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The intracellular delivery of nanomaterials and drugs has been attracting increasing research interest, mainly because of their important effects and functions in several organelles. Targeting specific organelles can help treat or decrease the symptoms of diabetes, cancer, infectious, and autoimmune diseases. Tuning biological and chemical properties enables the creation of functionalized nanomaterials with enhanced intracellular uptake, ability to escape premature lysosome degradation, and to reach a specific target. Here, we provide an update of recent advances in the intracellular delivery mechanisms that could help drugs reach their target more efficiently.

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“…Over the last decades, many studies have described attempts to hijack these systems for oral delivery of therapeutic peptides and proteins by conjugating the protein of interest to the natural ligands of these receptors in the hope of increasing oral absorption and this topic has been the subject of many focused reviews. 2,27,37 As the metabolic requirements for the different essential nutrients differ, so does the capacity of their transporter systems. For example, the capacity for iron uptake via transferrin complex formation is high and it is estimated that up to 100 mg of transferrin gets secreted every day from the liver into the bile which is subsequently, upon binding of iron, reabsorbed into circulation via the lymph system.…”

Section: Ligand-modifications Targeting Transporters and Receptorsmentioning

confidence: 99%

Chemically modified peptides and proteins - critical considerations for oral delivery

2016

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Numerous approaches have been explored to date in the pursuit of delivering peptides or proteins via the oral route. One such example is chemical modification, whereby the native structure of a peptide or protein is tailored to provide a more efficient uptake across the epithelial barrier of the gastrointestinal tract via incorporation of a chemical motif or moiety. In this regard, a diverse array of concepts have been reported, ranging from the exploitation of endogenous transport mechanisms to incorporation of physicochemical modifications in the molecule, which promote more favorable interactions with the absorptive membrane at the cell surface. This review provides an overview of the modification technologies described in the literature and offers insights into some pragmatic considerations pertaining to their translation into clinically viable concepts.

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Orally active-targeted drug delivery systems for proteins and peptides

Cited by 36 publications

References 83 publications

Protein aggregation and its impact on product quality

Protein aggregation and its impact on product quality

Strategies for the enhanced intracellular delivery of nanomaterials

Chemically modified peptides and proteins - critical considerations for oral delivery

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