Supercritical CO2 Technique Research Articles

Corrigendum to “Preparation and characterization of 5-fluorouracil-loaded PLLA–PEG/PEG nanoparticles by a novel supercritical CO2 technique” [Int. J. Pharm. 436 (2012) 272–281

Corrigendum to “Preparation and characterization of 5-fluorouracil-loaded PLLA–PEG/PEG nanoparticles by a novel supercritical CO2 technique” [Int. J. Pharm. 436 (2012) 272–281

Preparation and characterization of 5-fluorouracil-loaded PLLA–PEG/PEG nanoparticles by a novel supercritical CO2 technique

In this work, 5-fluorouracil-loaded- poly(l-lactic)-polyethylene glycol/polyethylene glycol (5-FU-loaded-PLLA-PEG/PEG) nanoparticles were prepared using a novel reverse emulsion-solution enhanced dispersion by supercritical fluids (reverse emulsion-SEDS) technique in an effort to obtain an efficient drug delivery system. In the experiment, 5-FU and PEG were dissolved in water PLLA-PEG was dissolved in organic solution, the aqueous solution was added dropwise to the organic solution under magnetic stirring, a reverse emulsion was immediately formed. The reverse emulsion was dried by a SEDS process so that 5-FU-loaded-PLLA-PEG/PEG nanoparticles (5-FU-NPs) were obtained. The particle size, size distribution, surface morphology, and physical and chemical properties of the 5-FU-NPs were investigated by laser diffraction particle size analysis, scanning electron microscopy (SEM), Fourier transform infrared spectrometry (FTIR) and thermogravimetric analysis (TGA). The drug encapsulation efficiency (EE), drug loading (DL), in vitro release profile and pharmacokinetics of 5-FU-NPs in rat plasma were investigated by high-performance liquid chromatography (HPLC). The in vivo tumor inhibition effect, increase in lifespan and hepatotoxicity of placebo-NPs, 5-FU and 5-FU-NPs were determined using H22 tumor-bearing ICR mice. These results collectively suggest that 5-FU-NPs prepared using SEDS have potential anti-tumor applications as a controlled drug release dosage form without harmful drug toxicity.

Traditional Chinese Medicine Epimedium Release from PLGA/HA Scaffolds Prepared in Supercritical CO<sub>2</sub>

Traditional chinese medicine epimedium was introduced into the poly(D,L-lactide-co-glycolide) / hydroxyapatite (PLGA/HA) scaffolds by using a supercritical CO2 technique. The morphology, porosity, mechanical strength, degradation behaviors, and drug release kenitics of scaffolds with 1wt%, 5 wt% and 10 wt% of epimedium were determined. The results revealed that the micropores and macropores in the scaffolds were interconnect, and the addition of drug had little effect on the morphology of scaffolds. When the drug was at 10 wt% , the porosity and mechnical strength of scaffolds were deteriorated. The dosage of epimedium in scaffolds exhibits an signficant influence on weight loss of scaffolds and release kenitics of epimedium. Within the limits of our study, 5 wt% epimedium loaded scaffolds might be suitable for bone tissue egineering application.

Characterization and Biological Evaluation of Paclitaxel-Loaded Poly(l-lactic acid) Microparticles Prepared by Supercritical CO2

In this study, paclitaxel loaded poly( L-lactic acid) (PTX-PLLA) microparticles were prepared using solution enhanced dispersion by supercritical CO2(SEDS) technique. This supercritical antisolvent technique offers the advantage of negligible organic solvent residua in the drug loaded microparticles. Scanning electron microscopy (SEM) showed that microparticles exhibited rather spherical shape and small particle size with narrow particle size distribution. X-ray diffraction (XRD) and differential scanning calorimeter (DSC) indicated that PTX was amorphously dispersed in the PLLA matrix. The drug loading and encapsulation efficiency of PTX-PLLA microparticles were 14.33% and 62.68%, respectively. In vitro cytotoxicity evaluation of PTX-PLLA microparticles against nonsmall-cell lung cancer A549 and ovarian cancer SKOV3 cell lines indicated that PTX-PLLA had superior antiproliferation activity against the A549 and SKOV3 cell lines, compared with free PTX formulations. The cellular internalization of fluorescent microparticles was evidenced by fluorescence microscope and further confirmed by transmission electron microscopy (TEM). This was attributed to the efficient intracellular accumulation of PTX via cell phagocytosis and sustained release of PTX from PLLA matrix. The anticancer activity of PTX-PLLA was associated with PTX-induced cell apoptosis such as nuclear aberrations, condensation of chromatin and swelling damage in mitochondria. The cell apoptosis index detected by flow cytometry was higher in PTX-PLLA group than in free PTX. The PTX-PLLA formulation, which was obtained through micronization of PTX and encapsulation of micronized PTX into PLLA simultaneously in the SEDS process, significantly potentiated the anticancer activity of PTX.

Preparation of stabilized lidocaine particles by a combination of supercritical CO2 technique and particle surface control

Lidocaine particles were prepared by the rapid expansion of the supercritical fluids into aqueous solution (RESAS). About 150–300 nm lidocaine particles could be temporarily observed when collected in water at concentration of 10 mg/cc, but the particles developed into 50 μm needle crystals just 30 min later. To prevent the fast aggregation of the particles as well as further crystal growth, modifications on particle surfaces by adding surfactants and introduction of electrostatic repulsion between particles were conducted. When a surfactant (sucrose stearic acid ester S-1570) was added to the collecting aqueous solution, the particle growth was alleviated and no large needle crystals were formed. However, the long-term stability needs to be improved because the lidocaine particles tend to grow from submicron to a few microns in a few days even stored in the 1% S-1570 solution. Electrostatic repulsion between particles is found effective to stabilize the submicron particles during the storage. When the pH value of the aqueous solution with 1% S-1570 was adjusted to 8.5 by adding KOH, the lidocaine particles suspending in this solution showed good stability that the particle size was able to be controlled in submicron level in 3 months.

13C‐CPMAS and 1H‐NMR Study of the Inclusion Complexes of β‐Cyclodextrin with Carvacrol, Thymol, and Eugenol Prepared in Supercritical Carbon Dioxide

Beta-cyclodextrin (beta-CD) inclusion complexes with carvacrol (1), thymol (2), and eugenol (3) (components of essential oils of vegetable origin) were prepared by the supercritical CO2 technique, and their structural characterization was achieved by means of 1H-NMR in aqueous solution and 13C-CPMAS NMR in the solid state. Evidence of the formation of the inclusion complexes for all the examined systems was obtained by 1H-NMR in solution, while 2D-ROESY-NMR experiments were used to investigate the geometry of inclusion. In addition, the dynamics of these inclusion complexes in the kHz timescale was investigated by analysis of the 1H and 13C spin-lattice relaxation times in the rotating frame.