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therapeutics for the treatment of viral diseases and cancer. Simultaneously,
nucleotides can constitute a promising choice to promote molecular recogni-
tion. However, these substances need to be protected since they can be easily
recognized and degraded by different extracellular nucleases, resulting in poor
in vivo pharmacokinetic properties. The usually severe cytotoxic side effects
of nucleoside and nucleotide analogs, particularly myelotoxicity, can be par-
tially relieved by lipid derivatization of the phosphate group of the active
nucleotide. The resulting drug is amphiphilic and can be delivered to the
therapeutic target by incorporation in lipid-based nanovectors.
In this regard these investigators used simple models for both hydro-
philic and hydrophobic modifi ed/functionalized nucleotide - based drugs,
adenosine monophosphate (AMP), guanosine monophosphate (GMP), uri-
dine monophosphate (UMP), and cytidine monophosphate (CMP) (xantho-
sine monophosphates [XMPs]), along with two hydrophobically functionalized
nucleotides (nucleolipids), that is, the 1 - palmitoyl - 2 - oleoyl -
sn
- glycerol - 3 -
phosphoadenosine (POPA) and the hexadecylphosphoadenosine (HPA)
(Fig. 8.20). In these nucleolipids a nucleic base is enzymatically exchanged
with the choline head group of a lipid precursor. The resulting systems were
investigated mainly through SAXS and
31
P - nuclear
magnetic
resonance
(NMR) techniques.
The GMO-based LC phases used here can be easily regarded as membrane
models as a result of lipid type and bilayer occurrence. These lipid LC systems
have been shown to constitute suitable matrices to entrap either hydrophilic
nucleotides or amphiphilic nucleolipids and are therefore promising lipid-
based nanovectors to protect and deliver nucleotide-analog drugs. However,
a drastically different behavior regarding the long-term stability of the nanode-
vice is displayed. All these molecules contain a phosphate moiety. It has been
ascertained that in the case of the amphiphilic additives (POPA and HPA),
which locate at the GMO polar-apolar interface, the LC systems were found
endowed of high stability, more than 2 years. Differently, the hydrophilic XMP
molecules, which are located in the aqueous domain of the GMO LC phases,
undergo a hydrolysis process at the phosphoester bond due to a preferential
orientation with respect to the MO interface. The XMP degradation, within
about 4 months, causes an impressive alteration of the interface arrangement,
resulting in structural transition from cubic to hexagonal mesophase. It was
demonstrated that the relatively small amount of
HPO
2−
anion resulting from
the XMP hydrolysis were suffi cient to induce a cubic-to-hexagonal phase
transition as a result of different, and specifi c, interactions at the polar-apolar
interface that favored a reverse curvature. Murgia et al. (2009) concluded that
the presence of unesterifi ed phosphate groups in fully hydrophilic drug mol-
ecules (e.g., XMPs) may have dramatic effects on the stability of the lipid
bilayer of a biological membrane.
Amar-Yuli et al. (2011b) combined the potential of both liquid crystalline
structure as well as glycerol as cosolvent to enhance insulin thermal stability
and moderate the aggregation progress. Insulin was incorporated into several
modifi ed reverse hexagonal systems based on friendly surfactant and polyols
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