Chemistry Reference
In-Depth Information
Sodium diclofenac (Na-DFC) is a common NSAID (nonsteroid anti-
infl ammatory drug) used to treat mild to moderate pain, particularly when
infl ammation is also present. This study utilized the advantages of the H
II
mesophase as a transdermal vehicle, in addition to those of the CPPs as skin
penetration enhancers, for the development of improved drug delivery vehi-
cles in which the drug diffusion rate might be carefully controlled.
The selected CPPs, representing prominent members of these families,
were chosen for their great effi ciency and short length; their amino acid
sequences are the following: RALA
, RALARALARALRALAR, is a 16-
amino-acid peptide belonging to a synthetic family of CPPs, based on GALA,
amphipatic peptides named after their alanine-leucine-alanine repeats that
exhibit improved membrane permeability. “PEN,” penetratin (RQIKI-
WFQNRRMKWKK), is a 16-amino-acid sequence based on the active pen-
etrating peptide produced by the homeodomain of the antennapedia
homeoprotein. “NONA,” nonaarginine, RRRRRRRRR. Arginine was shown
to play a key role in CPP attachment to membranes; thus, much research was
done concerning the penetrating activity of polyarginine through membranes.
The maximal solubilization load of Na-DFC, RALA, and PEN into the H
II
structures were found to be 5 wt %, while NONA solubilization capacity was
6 wt %.
Small - angle X - ray scattering (SAXS) data of the Na - DFC - loaded systems
revealed that the drug caused shrinkage of the hexagonal channel diameter.
The lattice parameter sharply decreases from 57.55
″
±
0.5 Å in the blank system
to 51.55
0.5 Å in the 5-wt % loaded system (Fig. 8.7), leading at to denser
packing of the system. The investigators assumed that such a “kosmotropic
effect” of the Na-DFC might originate from the drug's location between the
GMO molecules, causing an enhancement of the interactions between them.
This assumption was supported by the slight increase in the domain lengths
of the hexagonal clusters in the presence of Na-DFC from 392 to 493
±
5 0 Å
(Fig. 8.7), hinting a stabilizing effect. The main effect appeared in the low
concentration regime, whereas the additional Na-DFC quantities had a weaker
infl uence. These effects were noticed until the system transformed into a micel-
lar structure.
In addition, differential scanning calorimety (DSC) results suggested
enhanced water binding in the presence of the drug. Shrinkage of the aqueous
columnar cylinders (as detected also by SAXS) caused a change in the struc-
ture curvature (curvature more concave toward the inner water phase) and
an increase in the fraction of the bound water at the expense of the free water
that populated the inner channels. It also indicated that Na-DFC interacts with
the surfactant tails, reducing the number of molecules that are free to partici-
pate in the melting process. Combined DSC measurements and attenuated
total refl ection (ATR)-Fourier transform infrared (FTIR) analysis led the
authors to conclude that Na-DFC solubilization effect was primarily mani-
fested at the interfacial region, when the drug intercalated between the GMO
molecules. Na - DFC infl uenced the intermolecular bonding at this molecular
region. It strengthened the interactions between GMO tails, loosened the
±
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