Key Engineering Materials Vols. 342-343

Abstract: Methoxy poly(ethylene glycol) (MPEG)-b-poly(ε-caprolactone) (PCL) diblock copolymer was synthesized by ring-opening of ε-caprolactone (ε-CL) in the presence of a monomer activator with the terminal alcohol of MPEG as an initiator. The temperature sensitive behavior of the prepared MPEG-PCL diblock copolymer solution was examined. The polymer solution formed translucent sol at the room temperature. As the temperature increased from room temperature, the sol became gel, indicating that the diblock copolymer solution at room temperature can form gel at body temperature. Brain-derived neurotrophic factor (BDNF) loaded MPEG-PCL diblock copolymer solution and Pluronic solution for comparison were prepared to examine the release behavior of BDNF. Pluronic gel exhibited nearly complete release of BDNF even at 2 day, while the release of BDNF in MPEG-PCL gel showed the prolonged release profile for 21 days. In this study, we confirmed that thermosensitive MPEG-PCL diblock copolymer in this work could utilize as a potential carrier of BDNF.

Abstract: 5-Fluorouracil-poly(L-lactide) (5-Fu-PLLA) microspheres have been co-precipitated in a process namely solution-enhanced dispersion by supercritical CO2 (SEDS). First, the 5-Fu is successfully micronized and then used to produce the 5-Fu-PLLA microspheres. The 5-Fu-PLLA microspheres synthesized in the SEDS process exhibited a rather spherical shape, smooth surface, and a narrow particle size distribution, where it ranged from 531 nm to 1280 nm, with a mean particle size of 793 nm. The dichloromethane residue in the 5-Fu-PLLA microspheres is 46 ppm. The average drug load of the 5-Fu-PLLA microspheres is 12.7%. The results of this study indicate that the SEDS process is an effective technique to co-precipitate 5-Fu and PLLA as composite microspheres.

Abstract: Three kinds of curcumin-loaded films (3wt%, 5wt%, 8wt%) were prepared using poly(lactic acid-co-glycol acid (PLGA) as the carrier of curcumin, and studied. The result of Fourier transform infrared spectroscopy (FTIR) and X-ray electron spectroscopy (XPS) show that the curcumin is dispersed in the PLGA films. High performance liquid chromatography (HPLC) analysis suggests that the release of curcumin can last 22-43 days. A fewer number of adhered and activated platelets are observed on the curcumin-loaded PLGA films. The activated partial thromboplastin time (APTT) increases for all curcumin-loaded films.

Abstract: To develop osmotic granule with semi-permeable membranes, we prepared the semipermeable membranes with different pore forming agent by using solvent casting method. The membrane was consisted of cellulose acetate, Eudragit® RS, hydroxypropylcellulose (HPC), and triethylcitrate (TEC) in the presence of PEG200, PEG1, 000, or dibutylsebacate(DBS) as a pore forming agent. The produced membranes were white and elastic and exhibited soft property on touch. The release amount of pore forming agent from membrane with different pore forming agent was measured in water dissolution media and the order was PEG200 > PEG1, 000 > DBS. The formation of pore in membrane was observed by morphological SEM image after dissolution. The pore formation and porosity of membrane depended on water solubility of pore forming agent. We confirmed that pores in porous semi-permeable membrane could be controlled by the pore forming agent.

Abstract: The inclusion complex of CO2-soluble peracetylated-β-cyclodextrin (PAc-β- CD), heptakis(2,3,6-tri-O-acetyl)-β-cyclodextrin, and highly water-soluble drug captopril, was prepared by a chemical solvent-free method using supercritical carbon dioxide. The captopril-PAc-β-CD inclusion complex was further confirmed by DSC and XRD studies. In- vitro release of captopril from an oily suspension confirmed that the dissolution rate of captopril was much retarded from the inclusion complex as a result of the hydrophobic properties of PAc-β-CD.

Abstract: Hydrophobically modified derivative of a γ-cyclodextrin, functionalized with perfluoro alkyl ester group, was prepared and investigated for its potential use as a sustained release carrier for water-soluble drug molsidomine, a peripheral nitrovasodilator used in the treatment of angina pectoris. The molecular encapsulation of molsidomine by the amphiphilic cyclodextrin, octakis(6-O-perfluorobutanoyl)-γ-cyclodextrin (γ-CyD-F), was confirmed by DSC and XRD studies. The in-vitro release of molsidomine from peanut oil suspensions into aqueous phase was found to be significantly retarded by the complexation with γ-CyD-F, mainly due to the hydrophobic properties of the γ-CyD-F.

Abstract: The rapid prototyping (RP) technology has advanced in various fields such as verification of design, and functional test. Recently, researchers have studied bio-materials to fabricate functional bio-RP parts. In this research, a nano composite deposition system (NCDS) was developed to fabricate three-dimensional functional parts for bio-applications. In the hybrid process, the material removal process by mechanical micro machining and/or the deposition process are combined. NCDS uses biocompatible or biodegradable polymer resin as matrix and various bioceramics to form bio-composite materials. To test drug release rate in vivo environment, two different types of drug delivery system (DDS) were fabricated using the bio-composite materials. 1) Container type DDS used poly(DL-lactide-co-glycolide acid)(50:50) and 5-fluorouracil as the drug composite while polycaprolactone(PCL) served as the container of the drug. 2) Scaffold type DDS formed porous microstructure with poly(DL-lactide-co-glycolide acid)(50:50) and 5-fluorouracil composite. The effect of geometry of the DDS on release rate of drug is under investigation.

Abstract: Supercritical carbon dioxide (scCO2) was used as a processing medium for the fabrication of drug encapsulated poly(DL-lactide-co-glycolide) (PLGA) monoliths for their potential application in the controlled release of water soluble drugs. Exposure of PLGA to scCO2 leads to effective plasticization and liquefaction due to the high solubility and interaction of the scCO2 in the copolymer. By exploiting this property, it was demonstrated that prolonged release formulations of molsidomine, a peripheral nitrovasodilator used to treat angina pectoris, can be prepared by chemical solvent-free, scCO2 assisted drug impregnation method. The in-vitro dissolution studies revealed that the release rates of drug from the porous polymer monoliths containing different amount of the drug samples were significantly retarded due to encapsulation of molsidomine into the PLGA matrix.

Abstract: Stability and disintegration of natural polyelectrolyte complex microspheres for protein drugs delivery have been extensively investigated because of their great influence on the drug release patterns. In this study, we tested stability of microspheres with alginate (Alg) core layered by either chitosan (Chi) or glycol chitosan (GChi) by examining release profiles of fluorophorelabeled bovine serum albumin (BSA) and lysozyme (Lys) from the microspheres. While GChi shell was disintegrated quickly, Chi-shell microspheres showed good stability in PBS. Disintegration of the coated layer induced the core material instable. The results indicated that while the charges of the shell material provided additional diffusion barrier against the protein release, the key factor to hold the proteins inside the microspheres was the integrity of the outer coating layer.

Abstract: To improve the specific accumulation in tumor sites and aqueous solubility of atRA, the core-shell type of folate-PEG-g-PEI/atRA nanoparticles were prepared by complexation between cationic PEI segments in the copolymers and anionic charged atRA, and then characterized by 1HNMR, ELS, XRD, and TEM. In vitro atRA release from the nanoparticles was investigated as a function of drug content in sink condition. Cytotocicity of atRA against HepG2, KB cell lines were also evaluated by MTT assay. The lower the drug content, the faster atRA release. atRA incorporated in folate-PEG-g-PEI/atRA nanoparticles showed much higher cytotoxic effect compared with atRA itself.