The combination of mechanochemical activation and self-propagating high-temperature synthesis (SHS) have widened the possibilities for both methods. For metallic systems, the investigation showed that a short-term mechanochemical activation of heterophase SHS products leads to singlephase and ultrafine intermetallides obtained from the elements by mechanical alloying. It was demonstrated that metastable phases, usually obtained by mechanical alloying, can be obtained from the equilibrium intermetallic compounds synthesized by SHS. Besides this, the investigations showed that preliminary mechanical activation, during which layered composites are formed from the initial elements, allows one to extend the concentration limits of SHS processes up to a solid solution region. The preliminary mechanical activation also allows production of single-phase ultrafine complex oxides.
Praziquantel
(PZQ) is one of the most widespread anthelmintic drugs. However, the frequent insufficient
application of PZQ after oral administration is associated with its
low solubility, penetration rate, and bioavailability. In the present
study, the permeation of PZQ through a 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) membrane was investigated to probe
glycyrrhizin-assisted transport. Glycyrrhizin (or glycyrrhizic acid,
GA), a natural saponin, shows the ability to enhance the therapeutic
activity of various drugs when it is used as a drug delivery system.
However, the molecular mechanism of this effect is still under debate.
In the present study, the transport rate was measured experimentally
by a parallel artificial membrane permeation assay (PAMPA) and molecular
dynamics (MD) simulation with DOPC lipid bilayers. The formation of
the noncovalent supramolecular complex of PZQ with disodium salt of
GA (Na2GA) in an aqueous solution was proved by the NMR relaxation
technique. PAMPA experiments show a strong increase in the amount
of the penetrating praziquantel molecules in comparison with a saturated
aqueous solution of pure drug used as a control. MD simulation of
PZQ penetration through the bilayer demonstrates an increase in permeability
into the membrane in the presence of a glycyrrhizin molecule. A decrease
in the free energy barrier in the middle of the lipid bilayer was
obtained, associated with the hydrogen bond between PZQ and GA. Also,
GA reduces the local bilayer surface resistance to penetration of
PZQ by rearranging the surface lipid headgroups. This study clarifies
the mechanism of increasing the drug’s bioavailability in the
presence of glycyrrhizin.
Inclusion complexes of albendazole (ABZ) with the polysaccharide arabinogalactan from larch wood Larix sibirica and Larix gmelinii were synthesized using a solid-state mechanochemical technology. We investigated physicochemical properties of the synthesized complexes in the solid state and in aqueous solutions as well as their anthelmintic activity against Trichinella spiralis, Hymenolepis nаna, Fasciola hepatica, Opisthorchis felineus, and mixed nematodoses of sheep. Formation of the complexes was demonstrated by means of intrinsic solubility and the NMR relaxation method. The mechanochemically synthesized complexes were more stable in comparison with the complex produced by mixing solutions of the components. The complexes of ABZ showed anthelmintic activity at 10-fold lower doses than did free ABZ. The complexes also showed lower acute toxicity and hepatotoxicity. These results suggest that it is possible to design new drugs on the basis of the ABZ:arabinogalactan complex that are safer and more effective than albendazole.
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