The overall goal of this paper was to develop poly(lactic-co-glycolic acid) nanoparticles (PLGA-NPs) of curcumin (CUR), named CUR-PLGA-NPs, and to study the effect and mechanisms enhancing the oral bioavailability of CUR. CUR-PLGA-NPs were prepared according to a solid-in-oil-in-water (s/o/w) solvent evaporation method and exhibited a smooth and spherical shape with diameters of about 200 nm. Characterization of CUR-PLGA-NPs showed CUR was successfully encapsulated on the PLGA polymer. The entrapment efficiency and loading rate of CUR were 91.96 and 5.75%, respectively. CUR-PLGA-NPs showed about 640-fold in water solubility relative to that of n-CUR. A sustained CUR release to a total of approximately 77% was discovered from CUR-PLGA-NPs in artificial intestinal juice, but only about 48% in artificial gastric juice. After oral administration of CUR-PLGA-NPs, the relative bioavailability was 5.6-fold and had a longer half-life compared with that of native curcumin. The results showed that the effect in improving oral bioavailability of CUR may be associated with improved water solubility, higher release rate in the intestinal juice, enhanced absorption by improved permeability, inhibition of P-glycoprotein (P-gp)-mediated efflux, and increased residence time in the intestinal cavity. Thus, encapsulating hydrophobic drugs on PLGA polymer is a promising method for sustained and controlled drug delivery with improved bioavailability of Biopharmaceutics Classification System (BCS) class IV, such as CUR.

To achieve superior therapeutic efficacy, the combination chemotherapy using two or more anticancer drugs in clinical practice has been generally accepted as a feasible strategy. On account of the concept of combination chemotherapy, co-delivery of anticancer drugs with nanotechnology gradually becomes a desired strategy and one of the research frontiers on modern drug delivery. In recent years, nano drug co-delivery system (NDCDS), which loads at least two anticancer drugs with different physicochemical and pharmacological properties into a combination delivery system, has achieved rapid development. NDCDS synergistically inhibited the growth of the tumor compared with the free drugs. In this review, we highlighted the current state of co-delivery nanoparticles and the most commonly used nanomaterial, discussed challenges and strategies, and prospect future development. ARTICLE HISTORY

Over recent decades, many studies have reported that hypocrellin A (HA) can eliminate cancer cells with proper irradiation in several cancer cell lines. However, the precise molecular mechanism underlying its anticancer effect has not been fully defined. HA-mediated cytotoxicity and apoptosis in human lung adenocarcinoma A549 cells were evaluated after photodynamic therapy (PDT). A temporal quantitative proteomics approach by isobaric tag for relative and absolute quantitation (iTRAQ) 2D liquid chromatography with tandem mass spectrometric (LC–MS/MS) was introduced to help clarify molecular cytotoxic mechanisms and identify candidate targets of HA-induced apoptotic cell death. Specific caspase inhibitors were used to further elucidate the molecular pathway underlying apoptosis in PDT-treated A549 cells. Finally, down-stream apoptosis-related protein was evaluated. Apoptosis induced by HA was associated with cell shrinkage, externalization of cell membrane phosphatidylserine, DNA fragmentation, and mitochondrial disruption, which were preceded by increased intracellular reactive oxygen species (ROS) generations. Further studies showed that PDT treatment with 0.08 µmol/L HA resulted in mitochondrial disruption, pronounced release of cytochrome c , and activation of caspase-3, -9, and -7. Together, HA may be a possible therapeutic agent directed toward mitochondria and a promising photodynamic anticancer candidate for further evaluation.

This work develops and validates an electrochemical approach for uric acid (UA) determinations in both endogenous (cell lysate) and physiological (serum) samples. This approach is based on the electrocatalytic reduction of enzymatically generated H(2)O(2) at the biosensor of uricase-thionine-single-walled carbon nanotube/glassy carbon (UOx-Th-SWNTs/GC) with the use of Th-SWNTs nanostructure as a mediator and an enzyme immobilization matrix. The biosensor, which was fabricated by immobilizing UOx on the surface of Th-SWNTs, exhibited a rapid response (ca. 2 s), a low detection limit (0.5 +/- 0.05 microM), a wide linear range (2 microM to 2 mM), high sensitivity (approximately 90 microA mM(-1) cm(-2)), as well as good stability and repeatability. In addition, the common interfering species, such as ascorbic acid, 3,4-dihydroxyphenylacetic acid, 4-acetamidophenol, etc., did not cause any interference due to the use of a low operating potential (-400 mV vs saturated calomel electrode). Therefore, this work has demonstrated a simple and effective sensing platform for selective detection of UA in the physiological levels. In particular, the developed approach could be very important and useful to determine the relative role of endogenous and physiological UA in various conditions such as hypertension and cardiovascular disease.

Chitosan-modified poly(lactic-co-glycolic acid) nanoparticles (CHI/PLGA NPs) loaded with 7-ethyl-10-hydroxycamptothecin (SN-38), named CHI/PLGA/SN-38 NPs, were successfully prepared using an oil-in-water (O/W) solvent evaporation method. The physicochemical properties of the novel NPs were characterized by DLS, Zeta potential, SEM, DSC, XRD, and FTIR. The encapsulation efficiency and drug loading content were 71.83 (±2.77)% and 6.79 (±0.26)%, respectively. In vitro drug release in the simulated gastric juice was lower than that in the intestinal juice. In situ single-pass intestinal perfusion (SPIP) studies indicated a dramatic improvement of drug absorption as a result of the synergistic effect between CHI and PLGA on P-glycoprotein (Pgp) inhibition. CHI/PLGA NPs showed high cellular uptake and low efflux for drugs in Caco-2 cells. The cytotoxicity studies revealed that CHI/PLGA NPs had a transient effect on the membrane integrity, but did not have an influence on cell viability. Based on the in vitro release studies, SPIP, and intracellular drug accumulation and transport investigations, we speculate rationally that CHI/PLGA NPs were mainly internalized in the form of intact NPs, thus escaping the recognition of enterocyte Pgp and avoiding efflux into the apical part of the enterocytes. After partial release of drugs inside the enterocytes, CHI/PLGA interfered with the microenvironment of Pgp and further weakened the Pgp-mediated efflux. Then, the drug-loaded NPs exited via the exocytose effect from the basal part of the enterocytes and entered the blood circulation. These results showed that CHI/PLGA NPs would be smart oral delivery carriers for antineoplastic agents that are also Pgp substrates.