An efficient and long-acting local anesthetic: ropivacaine-loaded lipid-polymer hybrid nanoparticles for the control of pain.

PURPOSE: Local anesthetics are used clinically for the control of pain following operation (including gastrointestinal surgery) or for the management of other acute and chronic pain. This study aimed to develop a kind of lipid-polymer hybrid nanoparticles (LPNs), which were constructed using poly(ethylene glycol)-distearoylphosphatidylethanolamine (PEG-DSPE) as the hydrophilic lipid shell and poly-ε-caprolactone (PCL) as the hydrophobic polymeric core. METHODS: Ropivacaine (RPV) was entrapped in the LPNs (RPV-LPNs) and the physicochemical and biochemical properties such as size, zeta potential, drug release, and cytotoxicity were studied. The long-lasting effects and safety aspects of the LPNs were evaluated in vitro and in vivo. RESULTS: The particle size and zeta potential of RPV-LPNs were 112.3±2.6 nm and -33.2±3.2 mV, with an entrapment efficiency (EE) of 90.2%±3.7%. Ex vivo permeation efficiency of LPNs was better than the drug solution. The RPV-LPNs exhibited a long-lasting in vivo anesthesia effect in both rats and mice. CONCLUSION: Considering the low cytotoxicity, the LPNs prepared here could be used as an efficient local anesthetic for the control of pain.

The methane monooxygenase intrinsic activity of kinds of methanotrophs.

Methanotrophs have promising applications in the epoxidation of some alkenes and some chlorinated hydrocarbons and in the production of a biopolymer, poly-beta-hydroxybutyrate (poly-3-hydroxybutyrate; PHB). In contrast with methane monooxygenase (MMO) activity and ability of PHB synthesis of four kinds of methanotrophic bacteria Methylosinus trichosporium OB3b, M. trichosporium IMV3011, Methylococcus capsulatus HD6T, Methylomonas sp. GYJ3, and the mixture of the four kinds of strains, M. trichosporium OB3b is the highest of the four in the activity of propene epoxidation (10.72 nmol/min mg dry weight of cell [dwc]), the activity of naphthalene oxidation (22.7 mmol/mg dwc), and ability in synthesis of PHB(11% PHB content in per gram dry weight of cell in 84 h). It could be feasible to improve the MMO activity by mixing four kinds of methanotrophs. The MMO activity dramatically decreased when the cellular PHB accumulated in the second stage. The reason for this may be the dilution of the MMO system in the cells with increasing PHB contents. It has been found that the PHB contents at the level of 1-5% are beneficial to the cells for maintenance of MMO epoxidation activity when enough PHB have been accumulated. Moreover, it was also found that high particulate methane monooxygenase activity may contribute to the synthesis of PHB in the cell, which could be used to improve the yield of PHB in methanotrophs.

Methanol production from CO(2) by resting cells of the methanotrophic bacterium Methylosinus trichosporium IMV 3011.

Methanol production from carbon dioxide was successfully achieved using resting cells of Methylosinus trichosporium IMV 3011 as biocatalysts. Carbon dioxide was reduced to methanol and extracellular methanol accumulation has been found in the carbon dioxide incubations. However, resting cells of methanotrophs have a finite or intrinsic methanol production capacity due to a limiting supply of intracellular reducing equivalent. It has been found that the catabolism of stored Poly-beta -Hydroxybutyrate (PHB) can provide intracellular reducing equivalents to improve the intrinsic methanol production capacity. The initial nitrogen and copper concentration in the culture medium were studied for the accumulation of PHB by M. trichosporium IMV 3011, to expand its potential uses in methanol production from carbon dioxide reduction. It appeared that the total methanol production capacity was increased with increasing PHB content in cells. Resting cells containing 38.6% PHB exhibited the highest total methanol production capacity. But higher PHB accumulation adversely affected the total methanol production capacity. The effects of methanol production process on the survival and recovery of M. trichosporium IMV 3011 were examined. The results showed that the methanol production from carbon dioxide reduction was not detrimental to the viability of methanotrophs.