Shijun Jiang

A self-assembled nanocarrier loading teniposide improves the oral delivery and drug concentration in tumor.

We attempted to improve the oral delivery of lipophilic teniposide to achieve higher drug concentration in tumor by self-assembled nanocarrier for further oral chemotherapy. The teniposide loaded self-assembled nanocarrier (TSN) was spherical nanometric particles with narrow size distribution. The intestinal absorption of teniposide from TSN was obviously improved 4.09- and 6.35-fold in duodenum and jejunum at 0.5h after oral administration, then significantly decreased with the prolongation of time. The cellular uptake of TSN in Caco-2 cell monolayer was significantly enhanced over 3 folds and increased with incubation time. Moreover, TSN could be internalized into Caco-2 cell monolayer through clathrin-mediated endocytosis pathway, and then mainly transported into the systemic circulation via portal vein and intestinal lymphatic pathway. The pharmacokinetic results indicated that the AUC(0-t) value of TSN in rats was significantly improved 5.41-fold than that of teniposide solution, moreover, the teniposide concentration in tumor from TSN was obviously improved over 7-fold in tumor bearing mice. The captured image indicated that the oral administered TSN could specifically accumulate in tumor in the xenograft model. Therefore, the self-assembled nanocarrier was promising to enhance the oral delivery of lipophilic teniposide and its concentration in tumor for oral chemotherapy.

Reversal of multidrug resistance by mitochondrial targeted self-assembled nanocarrier based on stearylamine.

Multidrug resistance (MDR) remains one of the major challenges for successful chemotherapy. Herein, we tried to develope a mitochondria targeted teniposide loaded self-assembled nanocarrier based on stearylamine (SA-TSN) to reverse MDR of breast cancer. SA-TSN was nanometer-sized spherical particles (31.59 ± 3.43 nm) with a high encapsulation efficiency (99.25 ± 0.21%). The MDR in MCF-7/ADR cells was obviously reduced by SA-TSN, which mainly attributed to the markedly reduced expression of P-gp, increased percentages in G2 phase, selectively accumulation in mitochondria, decrease of mitochondrial membrane potential, and greatly improved apoptosis. The plasma concentration of teniposide was greatly improved by SA-TSN, and the intravenously administered SA-TSN could accumulate in the tumor site and penetrate into the inner site of tumor in MCF-7/ADR induced xenografts. In particular, the in vivo tumor inhibitory efficacy of SA-TSN in MCF-7/ADR induced models was more effective than that of teniposide loaded self-assembled nanocarrier without stearylamine (TSN) and teniposide solution (TS), which verified the effectiveness of SA-TSN in reversal of MDR. Thereby, SA-TSN has potential to circumvent the MDR for the chemotherapy of breast cancer.

Porous starch based self-assembled nano-delivery system improves the oral absorption of lipophilic drug.

The therapeutic efficacy of lipophilic drugs is commonly restricted by the low systemic exposure after oral administration. In this work, a new delivery system combining the advantages of porous starch and self-assembled nanocarrier was designed to improve the oral absorption of lipophilic drugs. The lipophilic probucol loaded porous starch based self-assembled nano-delivery (PSN) system was developed and characterized. The probucol loaded nanocarrier (PLN) could be formed by self-assembly when PSN was dispersed into the gastrointestinal (GI) fluids. PLN was nanometer-sized particles with narrow size distribution and exhibited good stability in GI fluids. The aqueous solubility of probucol was increased over 50,000-fold by PSN delivery system and the cumulative release of lipophilic probucol was increased over 80% in GI fluids. The distribution of probucol in duodenum, jejunum and ileum was respectively improved 7.17, 15.99 and 33.61-fold by PSN. In particular, the oral bioavailability of probucol from PSN was greatly improved about 9.96-fold than that from free drug suspension and 3.71-fold higher than that from the directed adsorbed probucol loaded porous starch system, which effectively confirmed the high potential of the strategy in enhancing the oral absorption of lipophilic drugs.

Bile salts enhance the intestinal absorption of lipophilic drug loaded lipid nanocarriers: Mechanism and effect in rats

The purpose of this study was to elucidate the effect and possible mechanism of bile salts on the intestinal absorption of lipophilic drug loaded lipid nanocarriers in rats. Effects of sodium cholate (SC) on the characteristics, intestinal absorption, cellular uptake in Caco-2 cell monolayers and intestinal lymphatic transport of candesartan cilexetil loaded lipid nanocarriers (CLN) were investigated to clarify the possible mechanism. The intestinal absorption of candesartan from CLN was evidently improved over 16-fold compared with free drug suspension, and further significantly enhanced 1.79-fold after the addition of SC. The cellular uptake of CLN in Caco-2 cell monolayers at 37̊C and its colocalization with endoplasmic reticulum were obviously increased in the presence of SC. Moreover, the intestinal lymphatic transport of CLN was obviously enhanced by SC. These results implicated that bile salts could improve the cellular uptake of CLN in Caco-2 cell monolayers via the active processes and promote the intestinal absorption of CLN through the intestinal lymphatic pathway. Therefore, bile salts could be an important physiological factor affecting the intestinal absorption of lipophilic drugs loaded lipid nanocarriers.

Determination of inorganic ions in oil field waters by single-column ion chromatography

Abstract A new method to determine inorganic ions in oil field water by single-column ion chromatography is presented. On an anion-bonded column, using a mixture of sodium benzoate (1.5 m M ) and sodium citrate (0.1 m M ) as eluent, the Cl − , NO 3 − and SO 4 2 − in oil field water can be determined. On a cation-bonded column, using 1.5 m M HNO 3 as eluent, the Na + and K + in oil field water can be determined. If a mixture of oxalic acid and ethylene diamine (both at 1.5 m M ) is used as the eluent, then Mg 2 + , Ca 2 + , Sr 2 + and Ba 2 + can be determined. If the content of Cl − and Na + is much higher than that of other inorganic ions, the sample may be diluted to allow the determination of these ions. The proposed method is characterized by its simplicity, rapidity and accuracy. The results match those obtained with the current procedures used in oil fields.

Controlled synthesis of shell cross-linked magnetic micelles for efficient liver MR imaging

In this paper, we report the fabrication, characterization and ex vivo bio-distribution of Rhodamine B-labeled shell cross-linked magnetic micelles (RhB-SCL-MMs) as a T2-weighted magnetic resonance contrast agent. Three sizes of hybrid micelles (80, 130 and 180 nm) are synthesized and the size effects on the cytotoxicity and cell uptake in macrophage cells (RAW264.7) are evaluated. The ex vivo bio-distribution experiments confirm that the three sizes of RhB-SCL-MMs are mainly accumulated in the liver and spleen after intravenous injection, which suggests that the micelles could be used as an efficient MR contrast agent for liver imaging. In addition, no tissue toxicity is detected in tissue slice tests. The application of RhB-SCL-MMs of different sizes is demonstrated for magnetic resonance imaging (MRI) both in vitro and in vivo. A maximum r2 value of 320.7 mM−1 s−1 is obtained for the RhB-SCL-MMs with the highest loading amount of magnetite, which is much higher than that of the well-known, liver-specific, T2-weighted contrast agent Feridex (iron oxide, r2 = 108 mM−1 s−1). The in vivo MRI studies show that the contrast enhancement of RhB-SCL-MMs in the liver is dependent on the diameter of the micelles, where the 130 nm RhB-SCL-MMs exhibit the most significant enhancement. In addition, the multifunctional nanoparticles present promising application potential in liver tumor MR imaging through enhanced permeability and retention (EPR) effect. Therefore, these kinds of iron oxide-based cross-linked micelles could be used as excellent, safe MR contrast agents for the diagnosis of liver diseases or cancers.

Nano-based Drug Delivery System Enhances the Oral Absorption of Lipophilic Drugs with Extensive Presystemic Metabolism

Oral administration remains the most preferred route for the treatment of many diseases due to its convenience and adaptability. However, the presystemic metabolism may be an important barrier that prevents lipophilic drugs from achieving their pharmacological effects following oral delivery. Nano-based drug delivery system provides an effective strategy to reduce the presystemic metabolism and increase the systemic exposure of lipophilic drugs. In this review, we described the physiological factors affecting the presystemic metabolism of lipophilic drugs, intestinal transport of nanosystems, strategy of nanosystems to avoid the presystemic metabolism, and the current application of various oral nanosystems including lipid and polymeric nanocarriers. The nano-based drug delivery system has a lot of potential for reducing the presystemic metabolism and enhancing the bioavailability of orally administrated lipophilic drugs.

A High-Drug-Loading Self-Assembled Nanoemulsion Enhances the Oral Absorption of Probucol in Rats

The purpose of this study was to develop a high-drug-loading nanoemulsion by self-assembly to improve the oral absorption of high dosing poorly water-soluble drugs. Probucol was selected as a model drug and the probucol-loaded self-assembled nanoemulsion (PSN) was prepared and characterized. Moreover, the intestinal absorption and in vivo pharmacokinetic behavior of PSN were evaluated in rats after oral administration. The experimental results indicated that PSN was nanometer-sized droplets with the mean diameter of 40.32 ± 0.31 nm and polydispersity index of 0.184 ± 0.005. The aqueous solubility of probucol was remarkably increased after its incorporation into PSN. Compared with free drug suspension, the intestinal absorption of PSN was not significantly increased in duodenum, but obviously enhanced 3.62- and 13.1-fold in jejunum and ileum, respectively. In particular, the in vivo pharmacokinetic results indicated that the oral bioavailability of probucol was greatly improved 8.97-fold by PSN. Thereby, the high-drug-loading self-assembled nanoemulsion was very effective in enhancing the oral absorption of high-dosing poorly water-soluble drugs.

Directed Self-assembled Nanoparticles of Probucol Improve Oral Delivery: Fabrication, Performance and Correlation

ABSTRACTPurposeWe are reporting on the development of a unique drug delivery platform by directed self-assembly technique to improve the oral delivery of hydrophobic drugs.MethodsHerein, a series of probucol directed self-assembled nanoparticles (PDN) were developed with two components of probucol and surfactant such as Tween 20, Tween 80, D-alpha-tocopheryl polyethylene glycol 1,000 succinate (TPGS) and HS-15, which was respectively named as T20-PDN, T80-PDN, TP-PDN and HS-PDN. The formation of various PDNs was determined by in vitro characterization and the physicochemical properties of these PDNs were determined. Moreover, the performance of PDN in enhancing the oral delivery and possible correlation between the in vitro properties and in vivo performances were investigated.ResultsPDN was homogenous nanometer-sized particles with negative surface charge. The cellular uptake of probucol in Caco-2 cell monolayer was respectively increased 1.15, 1.82, 1.59 and 5.31-fold by these PDN. In particular, the oral bioavailability of these PDN was significantly improved 3.0, 4.1, 5.4 and 10.4 folds compared with the free drug suspension. The enhanced cellular uptake and oral bioavailability were correlated with the characters of involved surfactants and the particle size of PDN.ConclusionsThereby, the directed self-assembled nanoparticles could provide a new strategy for enhancing the oral delivery of hydrophobic drugs.