In vitro evaluation of chitosan-coated liposome containing both coenzyme Q10 and alpha-lipoic acid: Cytotoxicity, antioxidant activity, and antimicrobial activity.

BACKGROUND: Chitosan-coated liposome containing both coenzyme Q10 and alpha-lipoic acid (CCAL) was a novel multifunctional nano delivery system exhibited long-term stability at room temperature and high encapsulation efficiency. Which containing two kinds of antioxidants (coenzyme Q10 and alpha-lipoic acid) and two antibacterial agents (chitosan and alpha-lipoic acid). However, the further biocompatibility, such as cytotoxicity and antioxidant activity, and antimicrobial activity of CCAL, has not been systematically evaluated. OBJECTIVES: This study aims to evaluate the cytotoxicity, antioxidant activity and antimicrobial activity of CCAL. METHODS: This article evaluated the in vitro cytotoxicity and antioxidant activity of CCAL by CCK8 assay, and antimicrobial activity on Staphylococcus aureus and Escherichia coli was investigated. RESULTS: For antioxidant activity study, CCAL displayed significant antioxidant effect when compared with control group (P<.01). Finally, CCAL also exhibited antimicrobial activity, and CCAL showed stronger bactericidal effect with Gram-positive bacteria than Gram-negative bacteria. CONCLUSIONS: CCAL could be a potential antioxidant delivery system for cosmetics or pharmaceuticals without cytotoxicity and artificial preservatives free.

Stabilization of a non-aqueous self-double-emulsifying delivery system of rutin by fat crystals and nonionic surfactants: preparation and bioavailability study.

Literature examples of non-aqueous Pickering emulsions stabilized by fat crystals are very rare. Moreover, the applications of rutin are limited due to its low solubility in both water and oils (less than 0.10 mg g-1 and 0.25 mg g-1, respectively). Thus, herein, we developed an optimum formulation of a non-aqueous self-double-emulsifying delivery system (SDEDS) containing rutin and evaluated its oral bioavailability. The new formulation stabilized by fat crystals (glycerol monostearate, GMS) and nonionic surfactants was prepared via a two-step emulsification process. The presence of a mixture of GMS crystals and nonionic surfactants effectively improves the stability of the emulsions. The non-aqueous SDEDS spontaneously forms oil-in-oil-in-water (O/O/W) double emulsions in the gastrointestinal environment with the inner oil phase mainly containing the active ingredients. It is stable at both 4 °C and 25 °C for 30 days and could enhance the dissolution properties of the active ingredients. Furthermore, the protection of rutin against digestion-mediated precipitation was observed when the formulation contained a high concentration of GMS crystals. The oral absolute bioavailability of rutin obtained from SDEDS (8.62%) is 1.76-fold higher than that of the actives suspension (4.90%). Thus, the non-aqueous SDEDS is an attractive candidate for the encapsulation of water-insoluble and simultaneously oil-insoluble nutrients (such as rutin) and for use in oral delivery applications.

Evaluation of a new solid non-aqueous self-double-emulsifying drug-delivery system for topical application of quercetin.

This study aimed to the evaluation of a new solid non-aqueous self-double-emulsifying drug-delivery system (SDEDDS) for topical application of quercetin. The new formulation was prepared through two-step emulsification process and could spontaneously form oil-in-oil-in-water (O/O/W) double emulsions after dilution with aqueous medium, with inner oil phase mainly containing the drug. Solid state characterisation was performed by DSC and X-ray powder diffraction. Furthermore, the optimised QT-SDEDDS displayed sustained release profile and was found to be stable up to 30 days under 4 °C and 25 °C. Antioxidant capacities showed that quercetin could be protected by the solid non-aqueous SDEDDS. Compared with the quercetin ethanol aqueous solution, the QT-SDEDDS exhibited higher permeation ability, and significantly increased accumulation of quercetin in the skin. These studies demonstrated that the solid non-aqueous SDEDDS might be a promising carrier for topical application of poorly water-soluble and simultaneously poorly oil-soluble drugs, such as quercetin.

Industrialization of lipid nanoparticles: From laboratory-scale to large-scale production line.

This work aimed at developing a large-scale modular production line, which referred to coenzyme Q10 loaded-NLC as well as its continuous and scalable emulsification and homogenization process. The production line exhibited good control over the emulsification and homogenization process and enabled the particle size of NLC below 210nm at a throughput of 25kg/h (for lipid solution at a flow rate of 0.4kg/min). Among the several process parameters investigated, the size of the NLC was mainly influenced by the pre-emulsification temperature, homogenization pressure and homogenization. Suitable emulsification temperature (70°C), homogenization pressure (600, 800bar), and homogenization cycle (3, 4cycles) resulted in relatively smaller particles. These results proved that coenzyme Q10, a model active, had been successfully loaded into the NLC. Meanwhile, the large-scale production line can be effectively applied for continuous and modular production of NLC. The line had modern networking features-essential in the Internet age-and a modular design that was easily modified and upgraded. In addition, the long-term stability over 6month was monitored at 30°C and at 40°C to assess a potential effect of the laboratory scale and large scale on stability. All batches at room temperature and below were stable, and only a negligible increase in size was observed.

Transdermal solid delivery of epigallocatechin-3-gallate using self-double-emulsifying drug delivery system as vehicle: Formulation, evaluation and vesicle-skin interaction.

The present study investigated a self-double-emulsifying drug delivery system loaded with epigallocatechin-3-gallate to improve epigallocatechin-3-gallate skin retention. The long chain solid lipids (cetostearyl alcohol) and macadamia oil were utilized as a carrier to deliver the bioactive ingredient. Response surface methodology was used to optimize the formulation, and the solid lipid to total lipid weight ratio, concentration of epigallocatechin-3-gallate and hydrophilic surfactant on skin retention were found to be the principal factors. The optimum formulation with high encapsulation efficiency (95.75%), self-double-emulsification performance (99.58%) and skin retention (87.24%) were derived from the fitted models and experimentally examined, demonstrating a reasonable agreement between experimental and predicted values. Epigallocatechin-3-gallate-self-double-emulsifying drug delivery system was found to be stable for 3 months. Transdermal studies could explain a higher skin diffusion of epigallocatechin-3-gallate from the self-double-emulsifying drug delivery system compared with EGCG aqueous solution. In vitro cytotoxicity showed that epigallocatechin-3-gallate-self-double-emulsifying drug delivery system did not exert hazardous effect on L929 cells up to 1:10.

Analgesic effect of iridoid glycosides from Paederia scandens (LOUR.) MERRILL (Rubiaceae) on spared nerve injury rat model of neuropathic pain.

Iridoid glycosides of Paederia scandens (IGPS) is a major active component isolated from traditional Chinese herb P. scandens (LOUR.) MERRILL (Rubiaceae). The aim of the present study was to investigate the analgesic effect of IGPS on spared nerve injury (SNI) model of neuropathic pain. The SNI model in rats was established by complete transection of the common peroneal and tibial distal branches of the sciatic nerve, leaving the sural branch intact. The mechanical withdrawal threshold (MWT) in response to mechanical stimulation was measured by electronic von Frey filaments on day 1 before operation and on days 1, 3, 5, 7, 10, and 14 after operation, respectively. Nitric oxide synthase (NOS) activity and nitric oxide (NO) production of spinal cord were measured by spectrophotometry and its cyclic guanosine monophosphate (cGMP) content by radioimmunoassay, mRNA expression of inducible NOS (iNOS) and protein kinase G type I (PKG-I, including PKG Ια and PKG Iß) of spinal cord were analyzed by RT-PCR. There was a marked mechanical hypersensitivity response observed on day 1 after operation in SNI model, which accompanied with decreased MWT. Treatment with IGPS (70, 140, 280 mg/kg) significantly alleviated SNI-induced mechanical hypersensitivity response evidenced by increased MWT; as well as markedly decreased NOS activity, NO and cGMP levels. At the same time, IGPS (70, 140, 280 mg/kg) could also inhibit mRNA expression of iNOS, PKG Ια and PKG Iß in the spinal cord. The results suggested that IGPS possesses antinociceptive effect, which may be partly related to the inhibition of NO/cGMP/PKG signaling pathway in the rat SNI model of neuropathic pain.