Jungeun Lee

Amphotericin B-entrapping lipid nanoparticles and their in vitro and in vivo characteristics.

Lipid nanoparticles (LNPs) as nano-scale drug carriers that can entrap poorly water-soluble drugs such as amphotericin B (AmB) in aqueous solution with high drug entrapment efficiency were developed and their in vitro and in vivo characteristics were investigated. The AmB-entrapping plain, anionic and PEG (polyethylene glycol)-LNPs were prepared by using spontaneous emulsification and solvent evaporation (SESE) method. Mean particle size of the AmB-entrapping LNPs ranged from 72.9 to 159.1nm according to a variation of their lipid composition. The surface of AmB-entrapping PEG (0.2)-LNPs having 84.4+/-6nm of particle size was negatively charged showing -50.4+/-5mV of zeta-potential value. Entrapment efficiency of AmB in the PEG-LNPs reached up to 76.5+/-5%. Cytotoxicity of the AmB-entrapping LNPs against human kidney cells, 293 cells, was lower than those of the commercialized AmB-formulations such as Fungizone and AmBisome. Hematotoxicity of the AmB-entrapping LNPs against red blood cells was much lower than that of Fungizone but comparable to AmBisome. Antifungal activity in vitro of AmB-entrapping LNPs against Candida albicans and Aspergillus fumigatus was better than the commercialized AmB formulations showing their low minimum inhibitory concentration (MIC) for 90% of growth inhibition of fungi. The AmB-entrapping LNPs increased circulation half life of AmB in blood stream and it was comparable to AmBisome. Antifungal activity in vivo of the AmB-entrapping PEG-LNPs against Aspergillus fumigatus (ATCC 16424)-infected mice was superior to that of AmBisome. The drug-entrapping LNPs, especially PEG-LNPs, can be applicable to entrapment of poorly water-soluble drugs and enhancement of therapeutic efficacy by modulating pharmacokinetic behaviors and/or drug-related toxicities.

Genome Sequence of Sphingomonas sp. Strain PAMC 26621, an Arctic-Lichen-Associated Bacterium Isolated from a Cetraria sp.

The lichen-associated bacterial strain Sphingomonas sp. PAMC 26621 was isolated from an Arctic lichen Cetraria sp. on Svalbard Islands. Here we report the draft genome sequence of this strain, which could provide novel insights into the molecular principles of lichen-microbe interactions.

Draft Genome Sequence of a Sphingomonas sp., an Endosymbiotic Bacterium Isolated from an Arctic Lichen Umbilicaria sp.

Sphingomonas sp. strain PAMC 26617 has been isolated from an Arctic lichen Umbilicaria sp. on the Svalbard Islands. Here we present the draft genome sequence of this strain, which represents a valuable resource for understanding the symbiotic mechanisms between endosymbiotic bacteria and lichens surviving in extreme environments.

Genome Sequence of a Salinibacterium sp. Isolated from Antarctic Soil

The draft genome of Salinibacterium sp. PAMC 21357, isolated from permafrost soil of Antarctica, was determined. Here we present a 3.1-Mb draft genome sequence of Salinibacterium sp. that could provide further insight into the genetic determination of its cold-adaptive properties.

Genome Sequence of Pseudomonas sp. Strain PAMC 25886, Isolated from Alpine Glacial Cryoconite

Pseudomonas spp. have shown characteristics of efficiently metabolizing environmental pollutants and also producing exopolysaccharides known as biofilms. Here we present the draft genome sequence of Pseudomonas sp. strain PAMC 25886, which was isolated from glacier cryoconite in the Alps mountain permafrost region and which may provide further insight into biodegradative and/or biofilm-producing mechanisms in a cold environment.

Preparation of Lipid Nanoparticles Containing Paclitaxel and their in vitro Gastrointestinal Stability

Peroral administration is the most convenient one for the administration of pharmaceutically active compounds. Most of poorly water-soluble drugs administered via the oral route, however, remain poorly available due to their precipitation in the gastrointestinal (GI) tract and low permeability through intestinal mucosa. In this study, one of drug delivery carriers, lipid nanoparticles (LNPs) were designed in order to reduce side effects and improve solubility and stability in GI tract of the poorly water soluble drugs. However, plain LNPs are generally unstable in the GI tract and susceptible to the action of acids, bile salts and enzymes. Accordingly, the surface of LNPs was modified with polyethylene glycol (PEG) for the purpose of improving solubility and GI stability of paclitaxel (PTX) in vitro. PEG-modified LNPs containing PTX was prepared by spontaneous emulsification and solvent evaporation (SESE) method and characterized for mean particle diameter, entrapping efficiency, zeta potential value and in vitro GI stability. Mean particle diameter and zeta potential value of PEG-modified LNP containing PTX showed approximately 86.9 nm and -22.9 mV, respectively. PTX entrapping efficiency was about 70.5% determined by UV/VIS spectrophotometer. Futhermore, change of particle diameter of PTX-loaded PEG-LNPs in simulated GI fluids and bile fluid was evaluated as a criteria of GI stability. Particle diameter of PTX-loaded PEG-LNPs were preserved under 200 nm for 6 hrs in simulated GI fluids and bile fluid at when DSPE-mPEG2000 was added to formulation of LNPs above 4 mole ratio. As a result, PEG-modified LNPs improved stability of plain LNPs that would aggregate in simulated GI fluids and bile solution. These results indicate that LNPs modified with biocompatible and nontoxic polymer such as PEG might be useful for enhancement of GI stability of poorly water-soluble drugs and they might affect PTX absorption affirmatively in gastrointestinal mucosa.

Preparation of Dexamethasone-21-palmitate Incorporated Lipid Nanosphere: Physical Properties by Varying Components and Ratio of Lipid

Intraarticular corticosteroid injections for therapy of rheumatic arthritis are administered with the aim of optimal local anti-inflammatory effect at the injection site. Since the side effects of corticosteroidal drug, dexamethasone(DEX), administered at hish dose limited the therapeutic efficacy, there was a need to design a new drug delivery system for controlled release of dexamethasone. As a prodrug for continuous therapeutic efficacy, dexamethasone-21-palmitate(DEX-PAL) was prepared via esterification of palmitoyl chloride and dexamethasone. DEX-PAL was identified by NMR and MASS analysis. DEX-PAL or DEX was entrapped in lipid nanosphere which could be prepared by using a self emulsification-solvent evaporation method. Physicochemical characteristics such as mean particle diameter, zeta potential and drug loading efficiency of the lipid nanospheres were investigated with variation of either the kind of lipid or the lipid composition. The lipid nanospheres had a mean diameter nm and DEX-PAL loading efficiency of up to 95%. The drug loading efficiency increased with the increase of aliphatic chain length attached to the phospholipid. The incorporation of cationic lipid was very efficient for both reducing particle size of lipid nanospheres and enhancing drug loading efficiency. The lipid nanospheres containing DEX-PAL may be a promising novel drug carrier for the controlled release of the poorly water-soluble drugs.