Enhanced transdermal peptide delivery and stability by lipid conjugation: epidermal permeation, stereoselectivity and mechanistic insights

Namjoshi, Sarika, Toth, Istvan, Blanchfield, Joanne T., Trotter, Nicholas, Mancera, Ricardo L. and Benson, Heather A. E. (2014) Enhanced transdermal peptide delivery and stability by lipid conjugation: epidermal permeation, stereoselectivity and mechanistic insights. Pharmaceutical Research, 31 12: 3304-3312. doi:10.1007/s11095-014-1420-5


Author Namjoshi, Sarika
Toth, Istvan
Blanchfield, Joanne T.
Trotter, Nicholas
Mancera, Ricardo L.
Benson, Heather A. E.
Title Enhanced transdermal peptide delivery and stability by lipid conjugation: epidermal permeation, stereoselectivity and mechanistic insights
Journal name Pharmaceutical Research   Check publisher's open access policy
ISSN 0724-8741
1573-904X
Publication date 2014-12
Year available 2014
Sub-type Article (original research)
DOI 10.1007/s11095-014-1420-5
Open Access Status
Volume 31
Issue 12
Start page 3304
End page 3312
Total pages 9
Place of publication New York, NY, United States
Publisher Springer New York
Collection year 2015
Language eng
Formatted abstract
Purpose

Efficient delivery of therapeutic peptides to the skin will facilitate better outcomes in dermatology. The tetrapeptide AAPV, an elastase inhibitor with potential utility in the management of psoriasis was coupled to short chain lipoamino acids (Laa: C6-C10) to enhance the peptide permeation into and through human epidermis.

Methods

AAPV was conjugated to Laas by solid phase synthesis. Peptide stability, skin distribution and permeation, elastase activity and surface activity were determined.

Results

Laas increased peptide permeation into the skin. The permeation lag time and amount of peptide remaining in the skin increased with the carbon chain length of the Laa conjugate. We also demonstrated stereoselective permeation enhancement in favour of the D-diastereomer. Importantly, the elastase inhibition activity of the peptide was largely retained after coupling to the Laa conjugates, showing potential therapeutic utility. The Laa-peptide structures were shown to be surface active, suggesting that this surfactant-like activity coupled with enhanced lipophilicity may contribute to their interaction with and permeation through the lipid domains of the stratum corneum.

Conclusions

This study suggests that the Laa conjugation approach may be useful for enhancing the permeation of moderately sized peptide drugs with potential application in the treatment of skin disorders.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Chemistry and Molecular Biosciences
 
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