Targeted Delivery Methods for Anticancer Drugs.

Several drug-delivery systems have been reported on and often successfully applied in cancer therapy. Cell-targeted delivery can reduce the overall toxicity of cytotoxic drugs and increase their effectiveness and selectivity. Besides traditional liposomal and micellar formulations, various nanocarrier systems have recently become the focus of developmental interest. This review discusses the preparation and targeting techniques as well as the properties of several liposome-, micelle-, solid-lipid nanoparticle-, dendrimer-, gold-, and magnetic-nanoparticle-based delivery systems. Approaches for targeted drug delivery and systems for drug release under a range of stimuli are also discussed.

The tissue-specific "ferromagnetic attack" on hyperactivation of ATP synthesis by magnesium-25 in mitochondria.

A (25)Mg(2+)-operated hyper-activation of ATP synthesis has been investigated in mitochondria (Mt) isolated from iron-rich and iron-poor rat tissues: spleen, liver, skeletal muscle, myocardium, kidneys, brain. Both magnetic ((25)Mg) and non-magnetic ((24)Mg) magnesium isotopes were separately administered to estimate the degree of the ATP production related to the magnetic isotope effect (MIE) of (25)Mg(2+)as a function of the amount of Mt-endogenous iron ions. A strong but negative (r = -0.88) correlation between the (25)Mg-MIE degree and the Mt[Fe(2+)] values was found. The physical and biophysical mechanisms behind these phenomena, as well as the possible impact of these data on further biochemical and pharmacological studies involving (25)Mg-promoted nuclear spin selectivity in mitochondrial function, are under discussion.

Brain targeting of nerve growth factor using poly(butyl cyanoacrylate) nanoparticles.

The nerve growth factor (NGF) is essential for the survival of both peripheral ganglion cells and central cholinergic neurons in the basal forebrain. The accelerated loss of central cholinergic neurons during Alzheimer's disease may be a determinant cause of dementia, and this observation may suggest a possible therapeutic benefit from treatment with NGF. In recent years, convincing data have been published involving neurotrophic factors for the modulation of dopaminergic transmission within the brain and concerning the ability of NGF to prevent the degeneration of dopaminergic neurons. In this connection, the administration of NGF may slow down the progression of Parkinson's disease. However, NGF, as well as other peptidic neurotrophic factors, does not significantly penetrate the blood-brain barrier (BBB) from the circulation. Therefore, any clinical usefulness of NGF as a potential CNS therapy will depend on the use of a suitable carrier system that enhances its transport through the BBB. The present study investigates brain delivery of NGF adsorbed on poly(butyl cyanoacrylate) (PBCA) nanoparticles coated with polysorbate 80 and the pharmacological efficacy of this delivery system in the model of acute scopolamine-induced amnesia in rats as well as in the model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonian syndrome. As shown by the passive avoidance reflex (PAR) test, the intravenous administration of the nanoparticle-bound NGF successfully reversed scopolamine-induced amnesia and improved recognition and memory. This formulation also demonstrated a significant reduction of the basic symptoms of Parkinsonism (oligokinesia, rigidity, tremor). In addition, the efficient transport of NGF across the BBB was confirmed by direct measurement of NGF concentrations in the murine brain. These results demonstrate that the PBCA nanoparticles coated with polysorbate 80 are an effective carrier system for the transport of NGF to the central nervous system across the BBB following intravenous injection. This approach may improve the NGF-based therapy of age-related neurodegenerative diseases.

Fullerene-based low toxic nanocationite particles (porphyrin adducts of cyclohexyl fullerene-C(60)) to treat hypoxia-induced mitochondrial dysfunction in mammalian heart muscle.

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.