Oral administration has been the most common therapeutic regimen in various diseases because of its high safety, convenience, lower costs, and high compliance of patients. However, susceptible in hostile gastrointestinal (GI) environment, many drugs show poor permeability across GI tract mucus and intestinal epithelium with poor oral absorption and limited therapeutic efficacy. In recent years, nanoparticulate drug delivery systems (NDDS) have become a hot research spot because of their unique advantages including protecting drug from premature degrading and interacting with the physiological environment, increasing intracellular penetration, and enhancing drug absorption. However, a slight change in physicochemistry of nanoparticles can significantly impact their interaction with biological pathways and alter the oral bioavailability of drugs. Hence, this review focuses on the factors affecting oral bioavailability from two aspects. On the one hand, the factors are the biochemical and physiological barriers in oral drugs delivery. On the other hand, the factors are the nanoparticle properties including size, surface properties, and shape of nanoparticles.

Background: Combination chemotherapy of chemo-drugs and natural herbal drugs has been shown to be more advantageous than individual treatment with respect to enhancing cytotoxicity, alleviating toxicity and controlling the development of multidrug resistance (MDR). Purpose: The goal of this study is to construct a combined drug delivery system of curcumin liposomes (CUR-LPs) and paclitaxel liposomes (PTX-LPs) to enhance the anticancer activity and reverse the MDR of PTX. Methods: CUR-LPs and PTX-LPs were prepared by solvent evaporation method with optimal formulation composition. MTT assay was used to assess the effect of the combination of CUR-LPs and PTX-LPs treatments on the proliferation of A549/A549-T cells. In addition, the pharmacokinetic behaviors of the combination treatments were evaluated by HPLC. Results : The mixed liposomes were found to have negative zeta-potential (–17.91 ± 1.21 mV) and relatively uniform particle size (105.88 ± 3.19 nm) with a low polydispersity index (0.21 ± 0.016). IC50 of PTX for combination of CUR-LPs and PTX-LPs decreased in the range of 1.47–2.9 times and 1.59–2.5 times compared to the free-drug counterparts in A549 and A549-T cells, respectively. Superior cytotoxicity and higher synergy (CI< 0.4) were observed for the combination treatment with ratio of 40:1 (CUR-LPs:PTX-LPs) compared with the free-drug counterparts in both cell lines tested. Following intravenous administration in rats, liposomes presented higher bioavailability (CUR-LPs: 9.02 fold; PTX-LPs: 7.32 fold) compared to free drugs. Co-administration did not alter the respective pharmacokinetic behaviors. Conclusion: Overall, the present study presents a promising strategy for the development of compound formulations of CUR and PTX.

In this study, a pair of chiral baicalin (BA) derivatives were synthesized by combining BA with phenylalanine methyl ester based on molecular docking technology, namely BAD and BAL. Cell cytotoxicity trails showed that the cell growth inhibitory effects of both BAD and BAL were increased by 8- to 12-fold compared with BA on A549 cells. Flow cytometry showed that the apoptotic rates of 50 μg/mL BA, BAD, and BAL to A549 cells for 48 h were 17.94%, 24.32%, and 39.69%, respectively. Western blotting analysis showed that BAD and BAL could promote Bax, caspase-3, and caspase-9 expression and inhibit Bcl-2 expression by inhibiting the expression of p-Akt. The tumor inhibition rates of BA, BAD, and BAL in nude mice of tumor-bearing experiment lasting for 24 days were 35.01%, 53.30%, and 59.35%, respectively. These results in vitro and in vivo showed that BAL had higher antitumor activity than did BAD and BA, which were related to promotion of the apoptosis of tumor cells by inhibiting the expression of p-Akt on PI3K/Akt pathway. This study provides an experimental basis for the development of a new configuration of BA for the treatment of cancer.

Curcumin (CU) has shown broad anti-cancer effects. 5-fluorouracil (5-FU) has been a conventional chemotherapeutic agent for hepatocellular carcinoma. Unfortunately, the nonspecific cytotoxicity and multidrug resistance caused by long-term use limited the clinical efficacy of 5-FU. This study was aimed to investigate whether the combination of CU and 5-FU could generate synergistic effect in inhibiting the human hepatocellular carcinoma. The results of cytotoxicity test showed that compared with applying single drugs, the combination of CU and 5-FU (1:1, 1:2, 1:4, 2:1 and 4:1, mol/mol) presented stronger cytotoxicity in SMMC-7721, Bel-7402, HepG-2 and MHCC97H cells, while the combination groups are relatively insensitive to normal hepatocytes (L02). Among them, the molar ratio of 2:1 combination group showed strong synergistic effect in SMMC-7721cells. Then, western blotting assay further verified that the mechanism of the synergistic effect may be related to the inhibition of the expression of NF-κB (overall) and COX-2 protein. In addition, the synergistic effect was also validated in the xenograft mice in vivo. This research not only provides a novel and effective combination strategy for the therapy of hepatocellular carcinoma but also provides an experimental basis for the development of CU and 5-FU compound preparation.

Malignant tumor endangers seriously the health of all mankind. Multidrug resistance (MDR) is one of the main causes of clinical tumor chemotherapy failure. Curcumin (CUR) has not only antitumor activity but also reversing tumor MDR effect. CUR reverses tumor MDR via regulating related signal pathways or corresponding expressed proteins or gene. When combined with chemotherapeutic agents, CUR can be a chemotherapeutic sensitive agent to enhance chemotherapy efficacy and weaken tumor MDR. On the other hand, to improve the MDR reversal effect of CUR, its derivatives have been extensively studied. Therefore, this article mainly focuses on reviewing the application of CUR and its derivatives in MDR and its mechanism of reversing MDR.