Despite in vitro effect of PG on CYP A the

Despite in vitro effect of PG on CYP3A4, the pharmacokinetics of CBZ was not affected in rabbits. In vitro results are not necessarily extrapolated to in vivo model. St John’s Wort, in vitro CYP3A4 inducer, did not significantly affect the pharmacokinetic parameters of CBZ (Burstein et al., 2000).
We think that the suitable interpretation of our results that pioglitazone has the potential to cause drug–drug interactions through induction of CYP3A4 if sufficient concentration (50μM) is achieved in the liver.


Conflict of Interest


Anthracycline-based buy Gefitinib such as doxorubicin (DOX), pirarubicin and daunorubicin have found widespread application in cancer chemotherapy. DOX is an anthracycline commonly used to treat several solid tumors, acute leukemia and malignant lymphoma (Kawano et al., 2003; Daemen et al., 1997; Mady et al., 2012). DOX can inhibit the replication process of cells by crossing the tumor cellular membrane and intercalating into the base pairs of DNA (Shi et al., 1993). However, severe clinical side effects, such as cardiotoxicity and myelosuppression, are of major concern. The prevailing liposomal drug delivery system can provide a solution to this problem.
Three basic requirements need to be fulfilled if liposomes are to be successful in delivering drugs specifically to cancerous tissue: (i) prolonged blood circulation, (ii) sufficient tumor accumulation, (iii) controlled drug release and uptake by tumor cells with a release profile matching the pharmacodynamics of the drug. Passive targeting can result in increases in drug concentrations in solid tumors of several-fold relative to those obtained with free drugs (Rahman et al., 1986; Sapra and Allen, 2003). The mechanism of action of the liposomal drugs is thought to be due to sustained release of drug from the liposomes and diffusion of the released drug throughout the tumor interstitial fluid, with subsequent uptake of the released drug by tumor cells.
However, liposomes have been found to be plagued by rapid opsonization and by their being taken up by the reticuloendothelial system (RES) cells located mainly in the liver and spleen. In general, this rapid uptake of the liposomes leads to their having a short circulation time. This problem has been resolved by incorporating lipid-grafted polyethyleneglycol (PEG) into the liposome membrane. The incorporation of lipid-grafted PEG reportedly reduced the opsonization of the liposomes and consequently increased their circulation time (Allen et al., 1991; Papahadjopoulos et al., 1991; Mercadal et al., 1999; Lu et al., 2004).
PEG liposomal DOX has revealed an increased therapeutic efficacy and reduced cardiotoxicity compared to free DOX (Gabizon et al., 2003; Ogawara et al., 2008). However, there is little information on the therapeutic efficacy of PEG liposomal DOX in multidrug-resistant tumor-bearing animal model.
Generally, chemotherapeutic drugs are administered to cancer patients for a long term with low dosage to prevent severe side effects, which often causes the cancer cells to acquire the resistance against the chemotherapeutic drug and the effectiveness of the drug gradually decreases. Resistance acquisition of the cancer cells by long-term exposure of the chemotherapeutic drugs, called “multidrug resistance”, has been considered as a major obstacle in the current clinical cancer chemotherapy (Chung et al., 1997).
However, except for the limited number of successful approaches that have launched into the clinical trial (Barraud et al., 2005), the outcomes from most of the approaches especially in the in vivo studies have been found to be still unsatisfactory to overcome the multidrug resistance of cancer cells.

Materials and methods

Results and discussion
The efficacy of drug delivery system has been assessed in vitro using cell viability assay (SBR assay). The cytotoxicity of free DOX and DOX loaded liposomes on HCT-15 colon cancer cell line has been measured. Compared with free drug, the synthesized Dox liposomes buy Gefitinib exhibit remarkable cytotoxicity. Two days post drug application, the IC50 values of free drug and DOX loaded liposomes formulation were 4.5μg/ml and 35.5μg/ml, respectively, (Fig. 1). For free doxorubicin treated cells, the percentage of cell viability decreased as the drug concentration increased. This is due to the anticancer effect of doxorubicin. For DOX loaded liposome treated cells, the marked increase in the IC50 value may be attributed to the sustained release of doxorubicin from liposomes. So, as the concentration of the encapsulated drug increases, the amounts of released drug also increase and consequently the cell viability decreases when the encapsulated drug concentration increases.