Factors of importance for a successful delivery system for proteins

Weert, Marco van de; Jørgensen, Lene; Moeller, Eva Horn; Frøkjær, Sven

doi:10.1517/17425247.2.6.1029

Cited by 36 publications

(18 citation statements)

References 77 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…No curative treatment is yet available for these amyloid diseases, which include Alzheimer's disease and type II diabetes [3]. Also, in the pharmaceutical development of stable protein drugs against life-threatening and seriously debilitating diseases such as diabetes, cancer, and rheumatoid arthritis [4], fibrillation is an undesirable phenomenon. Fibril formation is unwanted both from the point of view of adequate shelf life of the pharmaceutical and from the point of view of patient safety [5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Binding mode of Thioflavin T and other molecular probes in the context of amyloid fibrils—current status

2009

View full text Add to dashboard Cite

Because understanding amyloid fibrillation in molecular detail is essential for development of strategies to control amyloid formation and overcome neurodegenerative disorders, increased understanding of present molecular probes as well as development of new probes are of utmost importance. To date, the binding modes of these molecular probes to amyloid fibrils are by no means adequately described or understood, and the large number of studies on Thioflavin T (ThT) and Congo Red (CR) binding have resulted in models that are incomplete and conflicting. Different types of binding sites are likely to be present in amyloid fibrils with differences in binding modes. ThT may bind in channels running parallel to the long axis of the fibril. In the channels, ThT may bind in either a monomeric or dimeric form of which the molecular conformation is likely to be planar. CR may bind in grooves formed along the β-sheets as a planar molecule in either a monomeric or supramolecular form.

show abstract

Section: Introductionmentioning

confidence: 99%

Binding mode of Thioflavin T and other molecular probes in the context of amyloid fibrils—current status

2009

View full text Add to dashboard Cite

show abstract

“…Micron-sized needles porate skin in a minimally invasive manner to enable delivery of proteins. Similarly, all the enhancement methods enable delivery of drugs in different ways and bioavailabilites of ≥50% may be possible (3).…”

Section: Introductionmentioning

confidence: 99%

Transdermal Delivery of Proteins

2011

View full text Add to dashboard Cite

Abstract. Transdermal delivery of peptides and proteins avoids the disadvantages associated with the invasive parenteral route of administration and other alternative routes such as the pulmonary and nasal routes. Since proteins have a large size and are hydrophilic in nature, they cannot permeate passively across the skin due to the stratum corneum which allows the transport of only small lipophilic drug molecules. Enhancement techniques such as chemical enhancers, iontophoresis, microneedles, electroporation, sonophoresis, thermal ablation, laser ablation, radiofrequency ablation and noninvasive jet injectors aid in the delivery of proteins by overcoming the skin barrier in different ways. In this review, these enhancement techniques that can enable the transdermal delivery of proteins are discussed, including a discussion of mechanisms, sterility requirements, and commercial development of products. Combination of enhancement techniques may result in a synergistic effect allowing increased protein delivery and these are also discussed.

show abstract

“…Despite many attempts for transdermal, buccal, pulmonary or nasal delivery the common way to apply protein drugs is by subcutaneous injection or intravenous infusion [1,2]. As most proteins exhibit only short half-lives in-vivo [3], frequent injections/infusions are required to guarantee a sufficient plasma level of the drug. Implants offer a number of advantages over subcutaneous injection or intravenous infusion including longer dosing intervals, site-specific delivery of the drug, lower total drug loads, better patience compliance and more constant drug levels [2,4,5].…”

Section: Introductionmentioning

confidence: 99%