Advanced Biomaterials VII

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Authors: Hu Lin Jiang, Rohidas B. Arote, Ji Shan Quan, Mi Kyong Yoo, You Kyoung Kim, In Yong Kim, Zhong Shan Hong, Hong Gu Lee, Xun Jin, Yun Jaie Choi, Chong Su Cho
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.
Authors: In Young Park, Tae Hee Kim, You Kyoung Kim, Yun Jaie Choi, Jae Woon Nah, Chong Su Cho
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.
Authors: Ji Hye Seo, Hyun Seuk Moon, Ding Ding Guo, Hong Gu Lee, Yun Jaie Choi, Chong Su Cho
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.
Authors: Ji Shan Quan, Hu Lin Jiang, Yun Jaie Choi, Mi Kyong Yoo, Chong Su Cho
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.
Authors: Tae Hee Kim, Hua Jin, Hyun Woo Kim, Myung Haing Cho, Jae Woon Nah, Chong Su Cho
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.
Authors: Rohidas B. Arote, Tae Hee Kim, You Kyoung Kim, Dhananjay Jere, Hu Lin Jiang, In Young Park, Myung Haing Cho, Jae Woon Nah, Chong Su Cho
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.
Authors: You Kyoung Kim, In Kyu Park, Hu Lin Jiang, Rohidas B. Arote, Hwan Jeong Jeong, Eun Mi Kim, Myung Haing Cho, Hee Seung Bom, Chong Su Cho
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.
Authors: Yong Hee Kim
Abstract: Biodegradable in situ forming drug delivery systems that solidify or gel in the body from injectable fluids represent effective parenteral depot systems for controlled delivery of proteins. Various pharmaceutical additives were tested on their effectiveness as protein release modifiers and stabilizers. Mono-, di-, poly-saccharides, PEG2K and salting-out salts except cyclodextrins significantly decreased Tg of thermogelling polymers and their decreasing abilities were proportional to the polymer concentration and additive/polymer weight ratio up to solubility limits in aqueous media. For methyl cellulose (MC) gel, sodium carbonate, a strong salting-out salt, decreased Tg by 23 °C so that in situ gel can be formed at the body temperature. The incorporation of additives into thermogelling polymers significantly decreased the burst and retarded release kinetics. Although the pH inside gel gradually dropped down due to the polymer degradation, released model protein was confirmed to retain the original conformation.
Authors: Woo Dong Jang, Nobuhiro Nishiyama, Kazunori Kataoka
Abstract: A naphthalocyanine dendrimer (DNPcZn) was synthesized as a potential candidate of photosensitizer for photodynamic therapy. DNPcZn exhibited strong Q band absorption around 780 nm, a useful wavelength for high tissue penetration. A polyion complex (PIC) micelle (DNPcZn/m) system was formed via an electrostatic interaction of anionic DNPcZn and poly(ethylene glycol)-poly(L-lysine) block copolymers (PEG-b-PLL).
Authors: Dong Gon Kim, Min Ja Jang, Chang Yong Choi, Tae Hyeong Kim, Mi Kyeong Jang, Jae Woon Nah
Abstract: In this study, we prepared using low molecular weight water-soluble chitosan nanoparticle loaded paclitaxel (LMWSC-NPT) and investigated the potential as a drug carrier which is able to accumulate in the tumor site. In the experiment of receptor-mediated endocytosis, LMWSC-NPT was treated with sodium azid (NaN3) as an inhibitor of endocytosis process. As results, the antitumor activity of LMWSC-NPT treated with sodium azid didn’t show but LMWSC-NPT was shown the high antitumor activity. Therefore, LMWSC-NPs modified with hydrophobic group will be useful anticancer agent carrier via receptor-mediated endocytosis.

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