Visible-Light-Mediated Three-Component Decarboxylative Coupling Reactions to Synthesize 1,4-Diol Monoethers.

An efficient approach for 1,2-difunctionalization of aromatic olefins and the synthesis of functionalized 1,4-diols monoethers has been established via a photoinduced three-component reaction of an α-alkoxycarboxylic acid, an aromatic olefin, and an aldehyde. The reaction proceeds by photoinduced oxidative decarboxylation of the carboxylic acid followed by the addition of the α-alkoxyalkyl radical to the olefin, one-electron reduction of the addition radical, and the nucleophilic attack of the resulting carbanion to the aldehyde. Besides the convenient one-pot protocol of the three-component reaction, this method offers several other advantages, including good functional group tolerance for the three substrates, gentle reaction conditions, and ease of scaling up. The reaction mechanism has been investigated through free radical trapping experiment and isotope labeling experiments.

Visible-light induced three-component reaction for α-aminobutyronitrile synthesis by C-C bond formation using quantum dots as photocatalysts.

We describe a three-component reaction of malononitrile, benzaldehyde and N,N-dimethylaniline using aluminium doped CdSeS/CdZnSeS(Al)/ZnS quantum dots (QDs) as visible light catalysts to synthesize α-aminobutyrilitriles at room temperature and under mild conditions. The reactions exhibit high functional group tolerance, and the well dispersed quantum dot catalysts are highly efficient with a turnover number (TON) greater than 1.1 × 103 and can be recycled at least three times without significant loss of catalytic activity.

Optimization on biodistribution and antitumor activity of tripterine using polymeric nanoparticles through RES saturation.

Systemic delivery of tripterine (TPR) is challenged by its insoluble property and unsuitable pharmacokinetics. This work aimed to develop polymeric nanoparticles (NPs) combined with the reticuloendothelial system (RES) saturation to improve the in vivo distribution and antitumor activity of TPR. TPR-loaded nanoparticles (TPR-NPs) were prepared by the low-energy emulsification/evaporation method and characterized with particle size, entrapment efficiency, and morphology. The resulting TPR-NPs were 75 nm around in particle size and displayed a sustained drug release in pH 7.4 medium. Pharmacokinetic studies revealed that TPR-NPs had the advantage in bettering the pharmacokinetic properties of TPR over the solution formulation. However, the ameliorative effect on pharmacokinetics was more significant in the case of RES saturation (i.e. preinjection of blank NPs). Preinjection of blank NPs followed by injection of TPR-NPs resulted in higher distribution of TPR into the tumor due to reduced sequestration of TPR-NPs by RES. In tumor-bearing mice (prostatic cancer model), TPR-NPs treatment with RES saturation exhibited a superior antitumor efficacy to free TPR and TPR-NPs alone. It can be concluded that formulating TPR into polymeric NPs in combination with RES saturation is an effective means to address the systemic delivery of TPR.

Selenium-coated nanostructured lipid carriers used for oral delivery of berberine to accomplish a synergic hypoglycemic effect.

Diabetes mellitus is an incurable metabolic disorder that seriously threatens human health. At present, there is no effective medication available to defeat it. This work intended to develop selenium-coated nanostructured lipid carriers (SeNLCs) for enhancing the oral bioavailability and the curative effect of berberine, an antidiabetic phytomedicine. Berberine-loaded SeNLCs (BB-SeNLCs) were prepared by hot-melt dispersion/homogenization procedure followed by in situ reduction. BB-SeNLCs were characterized by particle size, morphology, entrapment efficiency (EE) and in vitro release. Pharmacokinetics of berberine solution, berberine-loaded NLCs (BB-NLCs) and BB-SeNLCs were studied in Sprague Dawley rats administered by oral gavage. The prepared BB-SeNLCs were around 160 nm in particle size with an EE of 90%. In addition, BB-SeNLCs exhibited a better sustained release of berberine compared to the plain NLCs. After oral administration, BB-SeNLCs greatly enhanced the oral bioavailability of berberine, which was approximately 6.63 times as much as that of berberine solution. The hypoglycemic effect of BB-SeNLCs was also significantly superior to that of BB-NLCs and berberine solution. It turned out that sustained drug release and good intestinal absorption, plus the synergy of selenium, were basically responsible for enhanced oral bioavailability and hypoglycemic effect. Our findings show that SeNLCs are promising nanocarriers for oral delivery of berberine to strengthen the antidiabetic action.

Biocompatible nanoemulsions based on hemp oil and less surfactants for oral delivery of baicalein with enhanced bioavailability.

Baicalein (BCL) possesses high pharmacological activities but low solubility and stability in the intestinal tract. This study aimed to probe the potential of nanoemulsions (NEs) consisting of hemp oil and less surfactants in ameliorating the oral bioavailability of BCL. BCL-loaded NEs (BCL-NEs) were prepared by high-pressure homogenization technique to reduce the amount of surfactants. BCL-NEs were characterized by particle size, entrapment efficiency (EE), in vitro drug release, and morphology. Bioavailability was studied in Sprague-Dawley rats following oral administration of BCL suspensions, BCL conventional emulsions, and BCL-NEs. The obtained NEs were ~90 nm in particle size with an EE of 99.31%. BCL-NEs significantly enhanced the oral bioavailability of BCL, up to 524.7% and 242.1% relative to the suspensions and conventional emulsions, respectively. BCL-NEs exhibited excellent intestinal permeability and transcellular transport ability. The cytotoxicity of BCL-NEs was documented to be low and acceptable for oral purpose. Our findings suggest that such novel NEs and preparative process provide a promising alternative to current formulation technologies and suitable for oral delivery of drugs with bioavailability issues.