PMID- 26623948
OWN - NLM
STAT- MEDLINE
DCOM- 20161005
LR  - 20161230
IS  - 1526-4602 (Electronic)
IS  - 1525-7797 (Linking)
VI  - 17
IP  - 1
DP  - 2016 Jan 11
TI  - Skin Penetrating Peptide as a Tool to Enhance the Permeation of Heparin through 
      Human Epidermis.
PG  - 46-55
LID - 10.1021/acs.biomac.5b01524 [doi]
AB  - This study aimed to identify a new skin penetrating peptide (SPP) able to enhance 
      unfractionated heparin (UFH) permeation through human epidermis by screening a 
      phage display peptide library. The effects of the synthesized heptapeptide 
      (DRTTLTN) on human stratum corneum organization were investigated by ATR-FTIR 
      spectroscopy and molecular dynamics simulation. The DRTTLTN penetration within 
      the human epidermis caused both a fluidization of the stratum corneum lipids and 
      the extension of keratins due to the increase of the contribution of alpha-helices. 
      The coadministration of DRTTLTN with UFH resulted ineffective in increasing skin 
      penetration due to UFH affinity for keratins. The conjugation of DRTTLTN to UFH 
      by N-(3-(dimethylamino)propyl)-N'-ethylcarbodiimide hydrochloride and sodium 
      N-hydroxysulfosuccinimide led to an increase of the flux of 24-36-fold with 
      respect to raw UFH, depending on the adopted synthetic procedure. The new 
      compounds showed a decrease of the antifactor Xa activity of about 4-5 times. 
      DRTTLTN also permitted to increase the fluxes of small model molecules. In 
      conclusion, these data support the use of SPP to enhance the skin penetration of 
      poorly absorbed compounds even in the case of macromolecules as polysaccharides.
FAU - Gennari, Chiara G M
AU  - Gennari CG
AD  - Department of Pharmaceutical Sciences, Universita degli Studi di Milano , Via 
      Giuseppe Colombo, 71-20133 Milan, Italy.
FAU - Franze, Silvia
AU  - Franze S
AD  - Department of Pharmaceutical Sciences, Universita degli Studi di Milano , Via 
      Giuseppe Colombo, 71-20133 Milan, Italy.
FAU - Pellegrino, Sara
AU  - Pellegrino S
AD  - Department of Pharmaceutical Sciences, Universita degli Studi di Milano , Via 
      Giuseppe Colombo, 71-20133 Milan, Italy.
FAU - Corsini, Emanuela
AU  - Corsini E
AD  - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi 
      di Milano , Via Giuseppe Balzaretti, 9-20133 Milan, Italy.
FAU - Vistoli, Giulio
AU  - Vistoli G
AD  - Department of Pharmaceutical Sciences, Universita degli Studi di Milano , Via 
      Giuseppe Colombo, 71-20133 Milan, Italy.
FAU - Montanari, Luisa
AU  - Montanari L
AD  - Department of Pharmaceutical Sciences, Universita degli Studi di Milano , Via 
      Giuseppe Colombo, 71-20133 Milan, Italy.
FAU - Minghetti, Paola
AU  - Minghetti P
AD  - Department of Pharmaceutical Sciences, Universita degli Studi di Milano , Via 
      Giuseppe Colombo, 71-20133 Milan, Italy.
FAU - Cilurzo, Francesco
AU  - Cilurzo F
AD  - Department of Pharmaceutical Sciences, Universita degli Studi di Milano , Via 
      Giuseppe Colombo, 71-20133 Milan, Italy.
LA  - eng
PT  - Journal Article
DEP - 20151214
PL  - United States
TA  - Biomacromolecules
JT  - Biomacromolecules
JID - 100892849
RN  - 0 (Lipids)
RN  - 0 (Peptide Library)
RN  - 0 (Peptides)
RN  - 68238-35-7 (Keratins)
RN  - 9005-49-6 (Heparin)
SB  - IM
MH  - Adult
MH  - Epidermis/*metabolism
MH  - Female
MH  - Heparin/chemistry/*metabolism
MH  - Humans
MH  - Keratins/metabolism
MH  - Lipids/physiology
MH  - Middle Aged
MH  - Peptide Library
MH  - Peptides/*metabolism
MH  - Permeability/drug effects
MH  - Skin/*metabolism
MH  - Skin Absorption/drug effects
MH  - Spectroscopy, Fourier Transform Infrared/methods
EDAT- 2015/12/02 06:00
MHDA- 2016/10/07 06:00
CRDT- 2015/12/02 06:00
PHST- 2015/12/02 06:00 [entrez]
PHST- 2015/12/02 06:00 [pubmed]
PHST- 2016/10/07 06:00 [medline]
AID - 10.1021/acs.biomac.5b01524 [doi]
PST - ppublish
SO  - Biomacromolecules. 2016 Jan 11;17(1):46-55. doi: 10.1021/acs.biomac.5b01524. Epub 
      2015 Dec 14.