ng-Su Cho

METHOXY POLY(ETHYLENE GLYCOL) AND CAPROLACTONE AMPHIPHILIC BLOCK CO POLYMERIC MICELLE CONTAINING INDOMETHACIN. II: MICELLE FORMATION AND DRUG RELEASE BEHAVIORS

Amphiphilic diblock copolymer composed of methoxy poly(ethylene glycol) (MePEG) and e-caprolactone (e-CL) was prepared by polymerization of e-CL initiated with MePEG. MePEG/e-CL block copolymeric micelles containing indomethacin (IMC) were prepared by a dialysis method and evaluated as a novel drug carrier. The size of micelle formed was less than 200 nm, and the size distribution of the micelle showed a narrow and monodisperse unimodal pattern. Also, the micelles formed by a dialysis method exhibited spherical structures. The indomethacin content in nanospheres was about 42.2%, for those prepared using copolymer, having molecular weight of about 12 000 and polymer/IMC weight ratio of 1/1. A release rate of indomethacin from nanospheres was slow, and thus the release continued over 15 days. As the molecular weights of the copolymer and the amount of drug entrapped increased, the release rate decreased. These results indicated that the drug-loaded nanospheres could be useful as a novel drug carrier in injectable delivery systems for hydrophobic drugs.

Clonazepam release from core-shell type nanoparticles in vitro

Block copolymers consisting of poly(gamma-benzyl L-glutamate) (PBLG) as the hydrophobic block and poly(ethylene oxide) (PEO) as the hydrophilic block were synthesized and characterized. Core-shell type nanoparticles of the block copolymers (abbreviated as GE) were prepared by the diafiltration method. The particle size diameter obtained by dynamic light scattering of GE-1 (PBLG content: 60.5 mol%), GE-2 (PBLG content: 40.0 mol %), GE-3 (PBLG content: 124.4 mol %) copolymer was 309.9 +/- 160.9, 251.9 +/- 220.6 and 200.5 +/- 177.1nm, respectively. The shape of the nanoparticles by SEM or TEM was almost spherical. The critical micelle concentration of the block copolymers obtained by fluorescence spectroscopy was dependent on the chain length of hydrophobic PBLG. The micelle structure of the copolymers nanoparticle was very stable against sodium dodecyl sulfate. Clonazepam (CZ) was loaded onto the core part of the nanoparticle as the crystalline state. Release of CZ from the nanoparticles in vitro was dependent on the drug loading contents and PBLG chain length.

Effect of polymer complex formation on the cloud-point of poly(N-isopropyl acrylamide) (PNIPAAm) in the poly(NIPAAm-co-acrylic acid) : polyelectrolyte complex between poly(acrylic acid) and poly(allylamine)

Abstract Random copolymers of acrylic acid (AAc) and N-isopropylacrylamide (NIPAAm) were synthesized by free-radical polymerization. The copolymers were characterized for their temperature- and pH-responsive behaviour by cloud-point experiments. The influence of polyelectrolyte between poly(allyl amine) (PAA) and poly( L -lysine) (PLL) on the lower critical solution temperature (LCST) of a pH/temperature sensitive polymer was compared in the range of pH 2–12. A polyelectrolyte complex was prepared by mixing poly(NIPAAm-co-AAc) and PLL solutions as anionic and cationic polyelectrolytes, respectively. The LCSTs of PNIPAAm/water in the copolymers were strongly affected by the pH, the presence of polyelectrolyte solute and AAc content in the poly(NIPAAm-co-AAc). The influence of more hydrophobic PLL as polyelectrolyte on the cloud-point of PNIPAAm/water in the copolymer was stronger than that of PAA. It is thought that as the side chain length increases from C1 for PAA to C4 for PLL, the hydrophobicity of polyelectolyte complex increases, indicating that much more dehydration occurs around PNIPAAm.

Albumin release from bioerodible hydrogels based on semi-interpenetrating polymer networks composed of poly(ϵ-caprolactone) and poly(ethylene glycol) macromer

Poly(ethylene glycol) (PEG) macromers terminated with acrylate groups and semi-interpenetrating polymer networks (SIPNs) composed of poly(ϵ-caprolactone)(PCL) and PEG macromer were synthesized and characterized to obtain a bioerodible hydrogel that can be used for albumin delivery. Polymerization of PEG macromer resulted in the formation of cross-linked gels due to the multifunctionality of macromer. Glass transition temperature (Tg) and melting temperature (Tm) of PEG network and PCL in the SIPNs were inner-shifted, indicating an interpenetration of PCL and PEG chains. Water content in the SIPNs increased with increasing PEG weight fraction due to the hydrophilicity of PEG. The amount of albumin released from the SIPNs increased with higher PEG content in the SIPNs, higher drug loading, lower concentration of PEG macromer during the SIPNs preparation, and the higher molecular weight of PEG. The degradation rate of the SIPNs gels in vitro increased with increasing of PEG weight fraction.

Clonazepam release from core-shell type nanoparticles composed of poly(γ-benzyl L-glutamate) as the hydrophobic part and poly(ethylene oxide) as the hydrophilic part

Block copolymers consisting of poly(γ-benzyl L-glutamate) (PBLG) as the hydrophobic part and poly(ethylene oxide) (PEO) as the hydrophilic part were synthesized and characterized. Core shell type nanoparticles of the block copolymers (abbreviated GEG) were prepared by the dialysis method. Under fluorescence spectroscopy measurement, the GEG block copolymers were associated in water to form core shell type nanoparticles as polymeric micelles and the critical micelle concentrations (CMC) values of the block copolymers decreased with increasing PBLG chain length in the block copolymers. Transmission electron microscopy (TEM) observations revealed nanoparticles of spherical shapes. From dynamic light scattering (DLS) study, sizes of nanoparticles of GEG-1 and GEG-2 copolymer were 64.3 ± 28.7 nm and 28.9 ± 7.0 nm. The drug-loading contents of GEG-1 and GEG-2 nanoparticles were 15.2 and 8.3 wt %, respectively. These results indicated that the drug-loading contents were dependent on PBLG chain length in the copolymer. Then, the longer the PBLG chain length, the more the drug-loading contents. Release of clonazepam (CNZ) from the nanoparticles was slower in higher loading contents of CNZ than lower loading contents due to the hydrophobic interaction between PBLG core and CNZ.

Growth of L929 cells on polymeric films prepared by Langmuir-Blodgett and casting methods.

The growth and spreading of fibroblast, L929 cells, on various polymeric films prepared by the Langmuir-Blodgett (LB) and casting methods were investigated. L929 cells, which were cultivated on collagen and synthetic polymeric films prepared by the LB method, adhered and spread much more than those on synthetic films prepared by the casting method. This is explained by the fact that cell growth and cell spreading are suitable for L929 cells on the films having serum proteins that contain a high α-helix content, because LB films adsorbed those serum proteins estimated from the circular dichroism measurements of the films immersed in cell culture medium. An exponential relationship was observed from the plot of the cell density vs root mean square of roughness of the films, which is estimated by atomic force microscopy, whereas a linear relationship was observed from the plot of the spreading ratio vs the root mean square of roughness. It is suggested that the correlation between the cell growth or spreading ratio and surface roughness of the films where L929 cells were cultivated is considered to be more important than the correlation between the cell growth or spreading ratio and the contact angle of the films.

Clonazepam release from poly(DL-lactide-co-glycolide) nanoparticles prepared by dialysis method

Aim of this work is to prepare poly(DL-lactide-co-glycolide) (PLGA) nanoparticles by dialysis method without surfactant and to investigate drug loading capacity and drug release. The size of PLGA nanoparticles was 269.9±118.7 nm in intensity average and the morphology of PLGA nanoparticles was spherical shape from the observation of SEM and TEM. In the effect of drug loading contents on the particle size distribution, PLGA nanoparticles were monomodal pattern with narrow size distribution in the empty and lower drug loading nanoparticles whereas bi- or trimodal pattern was showed in the higher drug loading ones. Release of clonazepam from PLGA nanoparticles with higher drug loading contents was slower than that with lower loading contents.

Effect of ligand orientation on hepatocyte attachment onto the poly(N p-vinylbenzyl-o-β-D-galactopyranosyl-D-gluconamide) as a model ligand of asialoglycoprotein

The orientation effect of galactose ligand on hepatocyte attachment was investigated. Poly(N-p-vinylbenzyl-o-beta-D-galactopyranosyl-D-gluconamide )(PVLA), a beta-galactose-carrying styrene homopolymer, was used as a model ligand for the asialoglycoprotein receptors on hepatocytes. PVLA was transferred onto the poly(gamma-benzyl L-glutamate) (PBLG) or PBLG/poly(ethylene glycol) (PEG)PBLG Langmuir-Blodgett (LB) films as the monolayer level. The dichroic fluorescence values of the confocal microscope indicated that the PVLA transferred onto the LB films was located with a preferential orientation of its molecular axes with regard to the direction of the alpha-helix of polypeptide. Hepatocyte recognized well-oriented galactose moieties of the surface of PVLA through asialoglycoprotein receptors.

Drug release from pH-sensitive interpenetrating polymer networks hydrogel based on poly (ethylene glycol) macromer and poly (acrylic acid) prepared by UV cured method

Acrylate-terminated poly (ethylene glycol) (PEG) macromer was prepared by the reaction of PEG with acryloyl chloride. Photopolymerization of PEG macromer resulted in the formation of cross-linked PEG network. Interpenetrating polymer networks (IPNs) based on PEG and poly(acrylic acid) (PAA) was obtained via template polymerization of AA to the PEG network by UV curing. The swelling degree of the IPNs hydrogel increased with an increase of pH value due to the association-dissociation between carboxylic acid of PAA and ether of PEG through hydrogen bonding. The swelling-deswelling behavior proceeded reversibly for the IPNs upon changing pH. Release of indomethacin from the IPNs demonstrated “on-off” regulation with pH fluctuation.

Enhanced CEA production associated with aspirin in a culture of CW-2 cells on some polymeric films

Human colorectal adenocarcinoma tumor (CW2) cells were cultivated in RPMI 1640 media containing 0–7.5 mM aspirin and 10% fetal bovine serum for the production of carcinoembryonic antigen (CEA). By adding aspirin to the media, the production of CEA per cell increased by up to one hundred fold compared to cultivation in normal media containing no aspirin, even though the total cell concentration decreased with the increase in aspirin in the media. The production of CEA was also investigated for CW2 cells cultured on silk fibroin, poly(γ-benzyl-L-glutamate) and poly(γ-benzyl-L-glutamate)/poly(ethylene oxide) diblock copolymer films prepared by the Langmuir-Blodgett and casting methods. The highest production of CEA per cell was observed for the CW2 cells on poly(γ-benzyl-L-glutamate) and its diblock copolymer films prepared by the Langmuir-Blodgett method in the medium containing 5 mM aspirin after 168 hr of inoculation. This originates from the fact that the cell density on the films in the medium containing 5 mM aspirin was the lowest under these conditions. It is suggested that CW2 cells produce CEA more effectively when the cell growth is suppressed by addition of toxic chemicals such as aspirin or by culture on unfavorable films for cell growth.