Papers by Author: Chong Su Cho

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.

Abstract: Novel, biodegradable poly(ester amine)s (PEAs) were synthesized using hydrophobic polycaprolactone diacrylate (PCLDA) and highly cationic polyethylenimine (PEI). This novel gene carrier can form stable DNA complexes with particle sizes around 200 nm, and showing excellent transfection efficiency and relatively low cytotoxicity compared with PEI 25K. Effect of hydrophobicity on transfection efficiency and cytotoxicity was profound and was relatively important parameter for the success of gene delivery.

Abstract: Polypropylenimine (PPI) dendrimers have been used by many researchers as gene delivery carriers due to their high functionality. Glucose as a kind of carbohydrate is biocompatible and hydrophilic. In this study, we synthesized glucosylated PPI (G-PPI) dendrimers to reduce cytotoxicity. Glucose substitution of G-PPI dendrimers was determined by the sulfuric acid micromethod. The G-PPI dendrimer was complexed with plasmid DNA in various N/P ratios, and the complex was characterized. G-PPI dendrimers showed good DNA binding ability and high protection of DNA from nuclease attack. The G-PPI dendrimer had low cytotoxicity compared to PPI dendrimer by cytotoxicity assay. Also, transfection efficiency was influenced by glucosylation degree and the transfection efficiency for the G-PPI-5 was slightly higher than that of PPI dendrimer in HeLa cell line.

Abstract: The key strategy for the advancement of gene therapy is the development of an efficient targeted gene delivery system into cells. The targeted gene delivery system is especially important in non-viral gene transfer which shows the relatively low transfection efficiency. It also opens the possibility of selective delivery of therapeutic plasmids to specific tissues. Chitosan has been considered to be a good candidate for gene delivery system, since it is already known as a biocompatible, biodegradable, and low toxic material with high cationic potential. However, low specificity and low transfection efficiency of chitosan need to be overcome prior to clinical trial. In this study, we focused on the chemical modification of chitosan for enhancement of cell specificity and transfection efficiency. Also, the potential of clinical application was investigated.

Abstract: The aim of this study is to prepare mucoadhesive chitosan microspheres for protein drug to deliver to intestine through oral administration. The thiolated Eudragit was synthesized by reaction between L-cysteine hydrochloride and Eudragit® L-100. About 8 mol-% of cysteine was introduced to the Eudragit-cysteine conjugate. The conjugate was used to coat bovine serum albumin (BSA)-loaded chitosan microspheres. The average particle sizes of BSA-loaded thiolated Eudragit-coated chitsoan microspheres (TECMs) were 4.06±0.74 .m and the uniform sizedistribution was shown. The in vitro release of BSA from BSA-loaded TECMs was pH-dependent. Our results indicated that thiolated Eudragit might be a good candidate as a coating material for oral delivery of protein drug owing to mucoadhesive and pH-sensitive properties.

Abstract: The objective of this study is to investigate whether the PEGylated conjugated linoleic acid (PCLA) as an anti-cancer prodrug can have favorable stability, biological activity, and prevention of proliferation in MCF-7 breast cancer cells for anti-cancer when compared with conjugated linoleic acid (CLA) itself. The CLA was simply coupled to poly(ethylene glycol) (PEG) at melting state without solvent or catalyst through ester linkage between carboxylic group of CLA and hydroxyl one of PEG. The results showed that the half life of PCLA was 55h in cell culture medium at pH 7.4 and 37°C. Apoptosis of MCF-7 breast cancer cells were induced by not only CLA- but PCLA-treatment with increasing concentrations whereas PCLA increased cell viability when compared with CLA itself. These results indicate that the PCLA is a more stable and valuable prodrug in that it has good stability and inhibition of cancer cell proliferation.

Abstract: The strategies developed for gene delivery are generally classified into two categories of viral and non-viral vectors. The limitation of viral vectors, which have problems including toxicity, immunogenicity and inflammatory response has led to the development of a novel, synthetic vectors based on non-viral vectors. Chitosan, one of non-viral vectors, has been a good candidate in gene delivery field. Moreover, galactosylated chitosan (GC) had the specific recognition of hepatocytes by galactose in the GC. Also, carbonate apatite increased the rate of DNA endocytosis and the efficiency of gene transfer. We describe here a new concept for improving cell specificity and transfection efficiency by hybridization of carbonate apatite (CAp) with GC. The complex formation was confirmed by agarose gel electrophoresis. The complex optimized through controlling calcium ion and charge ratio was evaluated on the cell specificity and transfection efficiency.

Abstract: Thiolated polymers have been studied by many researchers because of the mucoadhesive properties of thiol group. Alginate is a natural and biocompatible polymer that has been widely used in drug delivery. In this study, thiolated chitosan microspheres (TCMs) were prepared by ionic gelation process with tripolyphosphate and then, the bovine growth hormone (BGH) was loaded as a model drug. Finally, the BGH-loaded TCMs (BTCMs) were coated with alginate to improve the stability in gastrointestinal (GI) track. The alginate-coated BTCMs (ABTCMs) were observed as spherical shapes. The average particle sizes of ABTCMs were 6.97±0.55 -m and the sizedistribution was shown uniformly. Release of BGH from ABTCMs was decreased by coating with alginate and increased rapidly with the change in medium pH from 1.2 to 7.4. Results indicate that the ABTCMs have a potential as a drug carrier for oral drug delivery.

Abstract: The objective of this study is to develop a new type of cationic nanoparticles for the intracellular drug delivery to breast cancer. Poly(ester amine) (PEA) based on polyethylenimine and polycaprolactone was synthesized to make cationic PEA nanoparticles for all-trans retinoic acid (RA). In the 1H-NMR study, the proton signals of RA appeared in the spectrum of RA-loaded PEA nanoparticles in CDCL3, whereas they disappeared in D2O, suggesting that hydrophobic inner-core with hydrophilic outer-shell formed in water. RA release was faster at lower drug content and RA was released over a period of 20 days. RA-loaded PEA nanoparticles showed enhanced cytotoxicity compared with RA itself, whereas nanoparticles of PEA themselves did not show it. These results indicated that the cationic PEA provided an efficient intracellular delivery of RA.

Abstract: Vectors are vital aspect of gene delivery system which decides the success of gene therapy. Efficient transfection with minimum or no toxicity, are two principal aims of any gene delivery system. In this our study, we rationally developed biodegradable water soluble poly(ßamino ester) (PAE) based on spermine (SPR) and poly (ethylene glycol) (PEG), by Michael-type addition reaction and further studied for its potential as a gene carrier. Confirmation of synthesized PAE was done by proton NMR spectroscopy. In gel retardation assay, the PAEs have shown good DNA binding ability over wide range of polyplexes. The addition of PEG over SPR resulted in a novel PAE with higher degree of safety and transfection efficiency as compared with polyethylenimine 25K (PEI) when studied in 293T human kidney carcinoma cells.