A novel polyethylene glycol mediated lipid nanoemulsion as drug delivery carrier for paclitaxel.

A novel polyethylene glycol 400 (PEG400) mediated lipid nanoemulsion as drug-delivery carrier for paclitaxel (PTX) was successfully developed. The formulation comprised a PEG400 solution of the drug (25mg/mL) that would be mixed with commercially 20% lipid emulsion to form PTX-loaded nanoemulsion (1mg/mL) prior to use. This two-vial formulation of PTX-loaded lipid nanoemulsion (TPLE) could significantly reduce extraction of reticuloendothelial system (RES) organs and increase tumor uptake, and exhibited more potent antitumor efficacy on bearing A2780 or Bcap-37 tumor nude mice compared to conventional PTX-loaded lipid nanoemulsion (CPLE). TPLE did not cause haematolysis and intravenous irritation response yet, and showed the same cytotoxicity against HeLa cells as Taxol®, and its LD50 was 2.7-fold higher than that of Taxol®, suggesting its good safety and druggability. In addition, TPLE displayed distinctly faster release of PTX, a greater proportion of PTX in phospholipids layer and a smaller share in oil phase than CPLE. From the Clinical Editor: This study demonstrates the feasibility and potential advantage of a novel PEG400-mediated two-vial formulation of lipid nanoemulsion as drug carrier for PTX in clinical application for the cancer therapy. FROM THE CLINICAL EDITOR: This team of investigators convincingly demonstrates the feasibility and potential advantage of a PEG400-mediated two-vial formulation of lipid nanoemulsion as drug carrier for PTX in cancer therapy, documenting superior safety and faster release of PTX compared to commercially available formulations.

Applications of poly(ethylene oxide) in controlled release tablet systems: a review.

To improve therapeutic effects and compatibility of patients, controlled release tablet systems based on polymers are of great interest for pharmaceutical technologies. Poly(ethylene oxide) (PEO) is a non-ionic linear hydrophilic and uncrosslinked polymer available in a number of molecular weights. It is synthesized by ethylene oxide and has many desirable properties for drug delivery applications. This review article aims to summary the recent developments on physicochemical properties of PEO and focus on the recent efforts and developments on PEO as oral controlled release matrix tablets, bioadhesive hydrophilic matrices and osmotic pump tablets. Commercial products employed PEO were also discussed.

Preparation, safety, pharmacokinetics, and pharmacodynamics of liposomes containing Brucea javanica oil.

Brucea javanica oil-loaded liposomes (BJOL) were prepared through thin film hydration method and characterized by transmission electron microscope, dynamic light scattering, and differential scanning calorimetry. Acute toxicity of B. javanica oil (BJO) in liposomes was assessed by determining the number of deaths of Kunming mice over intravenous treatment for 2 weeks. The pharmacokinetic behavior of the main active component (oleic acid) was studied in SD rats. The pharmacodynamics of BJOL was investigated using MMC-7721 cell lines and mice with Lewis lung cancer. The commercial emulsion of BJO (BJOE) was used as a reference. The data showed that BJOL had an average diameter of 108.2 nm with a zeta potential of -57.0 mV, drug loading of 3.60%, and entrapment efficiency of 92.40%. The area under curve of BJO in liposomes and emulsions were 2.31 and 1.15 mg min/ml, respectively. Compared with BJOE, mean residence time and elimination half-time (t(1/2)) increased 2.8- and 4.0-fold, respectively, and the clearance (CL) decreased 0.5-fold. In the acute toxicity test, the median lethal dose (LD(50)) of BJOE was 7.35 g/kg. In contrast, all mice treated with liposomes survived even at the highest dosage (12.70 g/kg). The IC(50) value of BJOL group was one third of that of BJOE group (p < 0.01), and a less weight loss was observed in the BJOL-treated animals (p < 0.05). In conclusion, the present study suggests that BJOL significantly decreased toxicity of BJO and enhance the antitumor activity. Therefore, liposomes may be a potential effective delivery vehicle for this lipophilic antitumor drug.

Exfoliated graphitic carbon nitride nanosheets as efficient catalysts for hydrogen evolution under visible light.

Graphitic carbon nitride nanosheets are extracted, produced via simple liquid-phase exfoliation of a layered bulk material, g-C3N4. The resulting nanosheets, having ≈2 nm thickness and N/C atomic ratio of 1.31, show an optical bandgap of 2.65 eV. The carbon nitride nanosheets are demonstrated to exhibit excellent photocatalytic activity for hydrogen evolution under visible light.

Comparison of anti-EGFR-Fab' conjugated immunoliposomes modified with two different conjugation linkers for siRNa delivery in SMMC-7721 cells.

BACKGROUND: Targeted liposome-polycation-DNA complex (LPD), mainly conjugated with antibodies using functionalized PEG derivatives, is an effective nanovector for systemic delivery of small interference RNA (siRNA). However, there are few studies reporting the effect of different conjugation linkers on LPD for gene silencing. To clarify the influence of antibody conjugation linkers on LPD, we prepared two different immunoliposomes to deliver siRNA in which DSPE-PEG-COOH and DSPE-PEG-MAL, the commonly used PEG derivative linkers, were used to conjugate anti-EGFR Fab' with the liposome. METHODS: First, 600 µg of anti-EGFR Fab' was conjugated with 28.35 µL of a micelle solution containing DSPE-PEG-MAL or DSPE-PEG-COOH, and then post inserted into the prepared LPD. Various liposome parameters, including particle size, zeta potential, stability, and encapsulation efficiency were evaluated, and the targeting ability and gene silencing activity of TLPD-FPC (DSPE-PEG-COOH conjugated with Fab') was compared with that of TLPD-FPM (DSPE-PEG-MAL conjugated with Fab') in SMMC-7721 hepatocellular carcinoma cells. RESULTS: There was no significant difference in particle size between the two TLPDs, but the zeta potential was significantly different. Further, although there was no significant difference in siRNA encapsulation efficiency, cell viability, or serum stability between TLPD-FPM and TLPD-FPC, cellular uptake of TLPD-FPM was significantly greater than that of TLPD-FPC in EGFR-overexpressing SMMC-7721 cells. The luciferase gene silencing efficiency of TLPD-FPM was approximately three-fold high than that of TLPD-FPC. CONCLUSION: Different conjugation linkers whereby antibodies are conjugated with LPD can affect the physicochemical properties of LPD and antibody conjugation efficiency, thus directly affecting the gene silencing effect of TLPD. Immunoliposomes prepared by DSPE-PEG-MAL conjugation with anti-EGFR Fab' are more effective than TLPD containing DSPE-PEG-COOH in targeting hepatocellular carcinoma cells for siRNA delivery.