Autologous stem cell therapy is the most promising alternative treatment in patients with chronic ischemic diseases, including ischemic heart disease and critical limb ischemia, which are characterized by poor prognosis related to serious impair of quality of life, high risk of cardiovascular events and mortality rates. However, one of the most serious shortcomings of stem cell transplantation are low survival after transplantation to the site of injury, as large number of stem cells are lost within 24 hours after delivery. Multiple studies suggest that combination of lipid-lowering drugs, statins, and stem cell transplantation might improve therapeutic efficacy in regenerative medicine. Statins are inhibitors of HMG-CoA reductase and belong to recommended therapy in all patients suffering from critical limb ischemia. Statins possess non-lipid effects which involve improvement of endothelial function, decrease of vascular inflammation and oxidative stress, anti-cancer and stem cell modulation capacities. These non-lipid effects are explained by inhibition of mevalonate synthesis via blocking isoprenoid intermediates synthesis, such as farnesylpyrophospate and geranylgeranylpyrophospate and result in modulation of the PI3K/Akt pathway. Moreover, statin-mediated microRNA regulation may contribute to the pleiotropic functions. MicroRNA interplay in gene regulatory network of IGF/Akt pathway may be of special significance for the treatment of critical limb ischemia. We assume further studies are needed for detailed analysis of statin interactions with microRNA at the molecular level and their link to PI3K/Akt and IGF/Akt pathway in stem cells, which are currently the most promising treatment strategy used in chronic ischemic diseases.

• MeSH
• atorvastatin * farmakologie   terapeutické užití   MeSH
• chronická kritická ischemie končetin * farmakoterapie   terapie   MeSH
• fosfatidylinositol-3-kinasy * metabolismus   MeSH
• ischemie * farmakoterapie   terapie   MeSH
• končetiny * krevní zásobení   MeSH
• kvalita života MeSH
• lidé MeSH
• statiny * farmakologie   terapeutické užití   MeSH
• transplantace kmenových buněk * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• atorvastatin * MeSH
• statiny * MeSH

Different batches of atorvastatin, represented by two immediate release formulation designs, were studied using a novel dynamic dissolution apparatus, simulating stomach and small intestine. A universal dissolution method was employed which simulated the physiology of human gastrointestinal tract, including the precise chyme transit behavior and biorelevant conditions. The multicompartmental dissolution data allowed direct observation and qualitative discrimination of the differences resulting from highly pH dependent dissolution behavior of the tested batches. Further evaluation of results was performed using IVIVC/IVIVR development. While satisfactory correlation could not be achieved using a conventional deconvolution based-model, promising results were obtained through the use of a nonconventional approach exploiting the complex compartmental dissolution data.

• MeSH
• atorvastatin chemie   terapeutické užití   MeSH
• farmaceutická chemie MeSH
• gastrointestinální trakt účinky léků   fyziologie   MeSH
• lidé MeSH
• tenké střevo účinky léků   MeSH
• uvolňování léčiv * MeSH
• zdravotnické prostředky MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• atorvastatin MeSH

The solubility, absorption and distribution of a drug are involved in the basic aspects of oral bioavailability Solubility is an essential characteristic and influences the efficiency of the drug. Over the last ten years, the number of poorly soluble drugs has steadily increased. One of the progressive ways for increasing oral bioavaibility is the technique of nanoparticle preparation, which allows many drugs to thus reach the intended site of action. Candesartan cilexetil and atorvastatin, belonging to class II of the biopharmaceutical classification system, were chosen as model active pharmaceutical ingredients in this study. Forty samples were prepared either by antisolvent precipitation/solvent evaporation method or by the emulsion/solvent evaporation technique with various commonly used surface-active excipients as nanoparticle stabilizers. All samples were analyzed by means of dynamic light scattering. The particle size of the determined 36 nanoparticle samples was to 574 nm, whereas 32 samples contained nanoparticles of less than 200 nm. Relationships between solvents and excipients used and their amount are discussed. Based on the results the investigated solvent evaporation methods can be used as an effective and an affordable technique for the preparation of nanoparticles.

• MeSH
• aceton chemie   MeSH
• atorvastatin MeSH
• benzimidazoly chemie   MeSH
• bifenylové sloučeniny MeSH
• dextrany chemie   MeSH
• dodecylsíran sodný chemie   MeSH
• kyseliny heptylové chemie   MeSH
• methylenchlorid chemie   MeSH
• nanokuličky chemie   MeSH
• polyethylenglykoly chemie   MeSH
• polysorbáty chemie   MeSH
• pomocné látky chemie   MeSH
• povrchově aktivní látky chemie   MeSH
• pyrroly chemie   MeSH
• rozpouštědla chemie   MeSH
• rozpustnost MeSH
• sodná sůl karboxymethylcelulosy chemie   MeSH
• tetrazoly chemie   MeSH
• velikost částic MeSH
• vysoušení MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aceton MeSH
• atorvastatin MeSH
• benzimidazoly MeSH
• bifenylové sloučeniny MeSH
• candesartan MeSH Prohlížeč
• carboxymethyl dextran MeSH Prohlížeč
• dextrany MeSH
• dodecylsíran sodný MeSH
• kyseliny heptylové MeSH
• methylenchlorid MeSH
• polyethylenglykoly MeSH
• polysorbáty MeSH
• pomocné látky MeSH
• povrchově aktivní látky MeSH
• pyrroly MeSH
• rozpouštědla MeSH
• sodná sůl karboxymethylcelulosy MeSH
• tetrazoly MeSH