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Local delivery to the affected area represents the optimal means by which advantageous pharmacological properties of curcumin may be fully exploited as currently, due to the biopharmaceutical limitations associated with this polyphenol, its full beneficial effects remain limited. Curcumin-containing liposomes coated with bioadhesive polymers of natural and synthetic origin (chitosan and Carbopol) were evaluated in vitro. For these purposes, an in vitro model of vaginal mucus was developed allowing the monitoring of curcumin permeability in the conditions mimicking vaginal environment. The model was optimized by varying the amounts of glycoproteins, as compared to the permeabilities determined through isolated bovine mucus. The strength of bioadhesion was evaluated using the isolated bovine mucosa. Both curcumin solution and non-coated curcumin liposomes served as controls. Bioadhesive polymers enabled significantly higher (p<0.05) curcumin permeability through the artificial and isolated bovine mucus compared to the controls. Polymer coating of liposomes resulted in an increase in their bioadhesiveness. Mucoadhesive liposomes can be considered as potential novel drug delivery systems intended for vaginal administration of curcumin.

Due to the observed in vitro pharmacokinetic interactions between AGE and investigated cardiovascular, antidiabetic and antiviral drugs, in vivo absorption changes are possible, but the magnitude of change depends on the most profound process involved (influx, efflux, passive diffusion) in compounds permeability.

The therapeutic efficacy of saquinavir and darunavir is affected by the presence of xenobiotics (such as garlic compounds) capable of modifying transporter-enzyme interplay. To ascertain the mechanism of interactions between antiretroviral drugs and garlic supplements and to identify the garlic constituents responsible, the hepatic pharmacokinetics of two antiretroviral drugs was investigated in the presence of garlic phytochemicals and aged garlic extract. For this purpose, rat liver slices and isolated rat hepatocytes were used. Aged garlic extract significantly inhibited saquinavir efflux from rat hepatocytes, while the efflux of darunavir significantly increased. Phytochemicals inducing distribution changes of saquinavir and darunavir were most probably flavonoids and lipophilic organosulfur compounds, respectively. All tested phytochemicals (except S-allyl L-cysteine) and aged garlic extract inhibited CYP3A4 metabolism of both drugs and modulated hepatic distribution of the corresponding saquinavir and darunavir metabolites. The competition between saquinavir and garlic constituent(s) for the same binding site on the efflux transporter and the positive cooperative effect between darunavir and garlic phytochemical(s), which bind to separate binding places on transporter, are the most probable mechanisms explaining the plasma profile changes, which could occur in vivo during concomitant consumption of antiretrovirals and garlic supplements.

Bioactive natural products are consumed as food, dietary supplements and to a lesser extent as pharmaceutical products. A vast number of phytochemicals present in plant-based functional foods and dietary supplements exert not only desired biological effects but also complex interactions, which demonstrate themselves as pharmacological effects. Phytochemicals can alter the pharmacokinetic properties of conventional pharmaceuticals by enzyme inhibition/activation (cytochrome P450, glutathione S-transferase, glucuronyl transferase), P-glycoprotein (Pgp) activation or inhibition, altered Pgp expression and membrane fluidity, modulated drug solubility and uptake, and others.1,2) The most common users of herbal medicines are elderly patients prone to conditions treated by chronic therapy with conventional medicines. Therefore, the interactions of herbal medicines with prescribed drugs are very likely in this subpopulation and could result in cases of clinically adverse reactions. 3,4) It is also important since the consumption of herbal medicines (such as the best selling representatives St. John's worth, ginseng, garlic, Echinacea, saw palmetto and kava) is rising continuously. 3,5) P-glycoprotein and multidrug resistance associated protein 2 (MRP-2) are ATP-dependent multidrug transporter proteins, expressed in several cancer cell lines and in normal tissues of liver, kidney, blood-brain barrier, placenta and small intestine.2,6,7) The intestinal secretion of drugs and/or their metabolites from enterocytes into the intestinal lumen by apically located efflux proteins constitutes a potential biochemical barrier that can limit the rate and extent of drug absorption.2,7) The modulatory effect of several food components has been established, especially on Pgp, while data on MRP-2 are sparse.2,8) High-throughput screening essays, utilizing Pgp, human liver microsomes and cDNA expressed cytochromes, have shown the influence of garlic, garlic preparations and other phytochemicals on Pgp activity and on cytochrome P (CyP) 450 2C9, 2C19, 2D, and 3A4 enzyme function.2,5,9,10) Garlic also significantly increased the activity of lipase and amylase, and decreased the activity of chymotrypsin, lactase and maltase.11) An interaction of garlic with CyP3A4 metabolism and Pgp transport was even suspected to cause the case of extreme gastrointestinal toxicity of ritonavir. 12)Garlic and its extracts are used in particular because of their cholesterol and blood pressure lowering effects and their ability to prevent infections, atherosclerotic processes and to improve circulation.3) Garlic supplements are available as powder, garlic essential oil, macerated garlic oil and as aged garlic extract (AGE).2,5,13) AGE is formulated by soaking sliced raw garlic (Allium sativum) in 5-20% aqueous ethanol for up to 20 months at room temperature. The extract is then filtered and concentrated under reduced pressure at low temperature. The content of water soluble compounds is relatively high, while that of oil-soluble compounds is low. 14) In the m...

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