ABSTRACT
A non-Markovian theory of population dynamics is to simulate the anti-cancer drug distribution between malignant and the hosting normal cell pools. The model takes into account both the cell life span and the proliferation rate differences. This new simulation approach looks promising for its potential to optimize a chemotherapeutic strategy by choosing the scheme with a higher degree of the drug-tumor selectivity. The pre-test designed simulation mode fits nicely the experimental data on Porphylleren-MC16 (PMC16) pharmacokinetics patterns including the allometric plots revealed for this novel medicinal nanoparticle possessing some anti-cancer potential and intervening into the oxygen-independent ATP production mechanisms.
ABSTRACT
BACKGROUND: This is the first report on the targeted delivery of fullerene-based low toxic nanocationite particles (porphyrin adducts of cyclohexyl fullerene-C(60)) to treat hypoxia-induced mitochondrial dysfunction in mammalian heart muscle. METHODS: The magnetic isotope effect generated by the release of paramagnetic (25)Mg(2+) from these nanoparticles selectively stimulates the ATP overproduction in the oxygen-depleted cell. RESULTS: Because nanoparticles are membranotropic cationites, they will only release the overactivating paramagnetic cations in response to hypoxia-induced acidic shift. The resulting changes in the heart cell energy metabolism result in approximately 80% recovery of the affected myocardium in <24 h after a single injection (0.03-0.1 LD(50)). CONCLUSIONS: Pharmacokinetics and pharmacodynamics of the nanoparticles suggest their suitability for safe and efficient administration in either single or multi-injection (acute or chronic) therapeutic schemes for the prevention and treatment of clinical conditions involving myocardial hypoxia.
