Mats of PVA nanofibres were successfully prepared by the electrospinning process
and were developed as carriers of drugs for a transdermal drug delivery system.
Four types of non-steroidal anti-inflammatory drug with varying water solubility
property, i.e. sodium salicylate (freely soluble in water), diclofenac sodium (sparingly
soluble in water), naproxen (NAP), and indomethacin (IND) (both insoluble
in water), were selected as model drugs. The morphological appearance of the
drug-loaded electrospun PVA mats depended on the nature of the model drugs. The
1H-nuclear magnetic resonance results confirmed that the electrospinning process did not
affect the chemical integrity of the drugs. Thermal properties of the drug-loaded
electrospun PVA mats were analysed by differential scanning calorimetry and
thermogravimetric analysis. The molecular weight of the model drugs played a major role
on both the rate and the total amount of drugs released from the as-prepared drug-loaded
electrospun PVA mats, with the rate and the total amount of the drugs released decreasing
with increasing molecular weight of the drugs. Lastly, the drug-loaded electrospun PVA
mats exhibited much better release characteristics of the model drugs than drug-loaded
as-cast films.
The optimization of DNA-cationic polymer complexation is crucial for nonviral gene delivery. Although physicochemical characterization of the interaction between DNA and cationic polymers has recently attracted more attention in the nonviral DNA delivery field, the literature on the effect of varying polycation charge density on DNA-cationic polymer complexation is still scarce. Thus, the aim of this study was to systematically assess the influence of the degree of ionization of a weak cationic polyelectrolyte (poly[2-(dimethylamino)ethyl methacrylate] or DMAEMA homopolymer) on its ability to form complexes with DNA. This was achieved by varying the solution pH from 4.0 to 8.0 and analyzing the resulting effects on the binding affinity, thermodynamic properties, complex size, and morphology. Lowering the solution pH led to higher degrees of ionization for the cationic polymer and hence greater binding affinities with DNA, as judged by the increased propensity of the former to displace ethidium bromide from DNA and also by relatively low monomer:nucleotide molar ratio (0.8:1) required to retard the migration of free DNA. Isothermal titration microcalorimetry studies further confirmed that a stronger interaction occurred at low pH than at high pH. By decreasing the pH from 8.0 to 6.6, K(obs) increased from 7.8 x 10(5) to 20.4 x 10(5) M(-1). More efficient condensation at low pH was demonstrated by the reduction of ethidium bromide fluorescence in the loading wells from gel electrophoresis, decreased complex sizes without agglomeration occurring at high polymer/DNA ratios, together with discrete and dense spherical complexes observed in TEM studies. This may be attributed to the presence of electrostatic stabilization from excess cationic polymer chains, which provide a repulsive shell around the polymer/DNA complex. The physicochemical data indicate that the increased degree of ionization for the DMAEMA homopolymer at lower pH results in higher binding affinity, smaller and more compact complexes, and more efficient condensation. These findings therefore highlight the importance of the degree of ionization on DNA complex formation for weak cationic polyelectrolytes.
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