PMID- 25655714
OWN - NLM
STAT- MEDLINE
DCOM- 20151130
LR  - 20150309
IS  - 1873-3476 (Electronic)
IS  - 0378-5173 (Linking)
VI  - 481
IP  - 1-2
DP  - 2015 Mar 15
TI  - Influence of chemical and structural features of low molecular weight heparins 
      (LMWHs) on skin penetration.
PG  - 79-83
LID - S0378-5173(15)00086-1 [pii]
LID - 10.1016/j.ijpharm.2015.02.001 [doi]
AB  - Low molecular weight heparins (LMWHs) are obtained from unfractionated heparin 
      (UFH) through different depolymerization methods (DM), which produce compounds 
      having specific chemical features and biological activity. It is then supposed 
      that LMWHs also exhibit different skin permeability properties. The current work 
      aimed to get an insight on the in vitro passive diffusion through human epidermis 
      of six commercially available LMWHs in comparison with UFH. The in vitro studies 
      were performed using Franz diffusion cells. Heparins samples were assayed 
      measuring the anti-factor Xa activity. Circular dichroism was used to evaluate 
      the effect of the counter-ion (sodium or calcium) on the chain flexibility. The 
      penetrated amounts after 24h (Q24) of sodium LMWHs were related to Mw by an 
      exponential relationship (R=-0.758). The flux resulted dependent by DM following 
      the rank order: beta-elimination (8-11 mIU/cm(2)h range)>deaminative cleavage (5-7 
      mIU/cm(2)h range)>radical depolymerization (0.1mIU/cm(2)h). Finally, the calcium 
      ion, reducing the chain flexibility, significantly affected the Q24 (0.001 +/- 
      0.000 and 0.157 +/- 0.049 IU/cm(2) for calcium and sodium nadroparin, 
      respectively). Both the lower Mw and the introduction of new residues at the 
      chain ends improved the skin penetration of LMWHs with respect to UFH (Q24=0.001 
      +/- 0.001 IU/cm(2)), with bemiparin and enoxaparin being the most interesting 
      compounds.
CI  - Copyright (c) 2015 Elsevier B.V. All rights reserved.
FAU - Franze, S
AU  - Franze S
AD  - Department of Pharmaceutical Sciences - Universita degli Studi di Milano, Via 
      Giuseppe Colombo 71, 20133 Milan, Italy.
FAU - Gennari, C G M
AU  - Gennari CG
AD  - Department of Pharmaceutical Sciences - Universita degli Studi di Milano, Via 
      Giuseppe Colombo 71, 20133 Milan, Italy.
FAU - Minghetti, P
AU  - Minghetti P
AD  - Department of Pharmaceutical Sciences - Universita degli Studi di Milano, Via 
      Giuseppe Colombo 71, 20133 Milan, Italy.
FAU - Cilurzo, F
AU  - Cilurzo F
AD  - Department of Pharmaceutical Sciences - Universita degli Studi di Milano, Via 
      Giuseppe Colombo 71, 20133 Milan, Italy. Electronic address: 
      francesco.cilurzo@unimi.it.
LA  - eng
PT  - Journal Article
DEP - 20150202
PL  - Netherlands
TA  - Int J Pharm
JT  - International journal of pharmaceutics
JID - 7804127
RN  - 0 (Heparin, Low-Molecular-Weight)
SB  - IM
MH  - Circular Dichroism
MH  - Heparin, Low-Molecular-Weight/chemistry/*metabolism
MH  - Humans
MH  - In Vitro Techniques
MH  - Permeability
MH  - Skin/*metabolism
MH  - Skin Absorption
OTO - NOTNLM
OT  - Chain flexibility
OT  - Circular dichroism
OT  - Human epidermis
OT  - LMWHs
OT  - Skin penetration
EDAT- 2015/02/07 06:00
MHDA- 2015/12/15 06:00
CRDT- 2015/02/07 06:00
PHST- 2014/12/16 00:00 [received]
PHST- 2015/01/30 00:00 [revised]
PHST- 2015/02/01 00:00 [accepted]
PHST- 2015/02/07 06:00 [entrez]
PHST- 2015/02/07 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
AID - S0378-5173(15)00086-1 [pii]
AID - 10.1016/j.ijpharm.2015.02.001 [doi]
PST - ppublish
SO  - Int J Pharm. 2015 Mar 15;481(1-2):79-83. doi: 10.1016/j.ijpharm.2015.02.001. Epub 
      2015 Feb 2.