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Infectious diseases induced by multidrug-resistant bacteria are a challenging problem in medicine because of global rise in the drug resistance to pathogenic bacteria. Despite great efforts on the development of antibiotics and antimicrobial agents, there is still a great need to develop a strategy to early detect bacterial infections and eradicate bacteria effectively and simultaneously. The innate immune systems of various organisms produce antimicrobial peptides, which kill a broad range of bacteria with minimal cytotoxicity to mammalian cells. Therefore, antimicrobial peptides have recently attracted increasing attention as an alternative to conventional antibiotics in antibacterial medications. Here, we report a new family of antibacterial agents, which is formulated from self-assembly of a chimeric antimicrobial lipopeptide (DSPE-HnMc) and amphiphilic biodegradable polymers. HnMc micelles could effectively bind the bacterial membrane to kill a wide spectrum of bacteria and bacterial biofilms. In the studies of mouse models of drug-resistant bacterial infections, HnMc micelles could target bacterial infections with high specificity and also kill drug-resistant bacteria effectively, demonstrating the great potential of HnMc micelles as imaging and targeted antibacterial agents. These findings also provide new insight into the design of antimicrobial peptide-based nanomedicine for detection and treatment of bacterial infections.

Targeting antitumor drugs to specific tissues or cells has attracted considerable interest in the recent tumor therapy because it can reduce the side effects in the body and the treated drug dosage through homing drug to the desired tissues. To utilize the high affinity of biotin to avidin as a drug carrier for doxorubicin (DOX), biotinylated targeting material (biotin-polyethylene glycol (PEG)-folic acid, BPF) and biotinylated drug with a bioreducible linker (biotin-SS-PEG-DOX, BSPD) were designed in this study. The in vitro cellular uptake of the avidin/biotinylated drug complexes showed that the complexes with BPF were internalized dose-dependently into HeLa cells, while their uptake was not detected in the absence of BPF. Although the anti-tumor activity of the drug complexes with BPF and BSPD were similar to that of free DOX in cervical cancer cells, the cytotoxic effect of DOX was significantly reduced in normal cells. Their targeting antitumor effect revealed the significant inhibition of the increasing tumor size in HeLa-xenograft mouse model. These results show that the strong complexing between avidin and biotin acted as a targeting moiety and the antitumor drug is an adaptable tool in the fields of tumor therapy.

Styrenated phenols are usually synthesized by the reaction of styrene and phenol under acid catalysts. Styrenated phenol involving high content of di-styrenated phenol (DSP) was synthesized, which can be used to prepare styrenated phenol alkoxylate. The solid catalyst used in this study was prepared by impregnation method. SO4 2- on SO4 2-/ZrO2 catalyst was introduced from an aqueous 1M-H2SO4 solution. The catalysts were characterized by SEM images, XRD patterns, and FT-IR spectra. The catalytic activity was examined by measuring the conversion of phenol and styrene in a liquid-phase batch reactor. Almost 100% conversion of both phenol and styrene over 15-SO4 2-/ZrO2 catalyst were obtained at reaction temperature of 100 °C and reaction time of 6 hr. Amount of catalyst to the reactants was 15 wt%. At same reaction conditions, selectivity of MSP, DSP, and TSP were 23.6%, 52.1%, and 5.4%, respectively. It was known that the selectivity to DSP was increased as IR absorption peak of 1236 cm-1 corresponding to O–S–O bonds was increased.

We developed a polyamidoamine (PAMAM) conjugated disulfide-linked chitosan (dsCS-PAM) for nonviral gene delivery. At weight ratio of 128, dsCS and dsCS-PAM showed positive zeta potential of around 9.5 mV and 14.5 mV, respectively, demonstrating their ability to form complexes with plasmid DNA (pDNA) for cell transfection. CS-PAM and dsCS-PAM formed complexes with pDNA in a reducing environment containing 5 mM DLdithiothreitol (DTT) at weight ratio 32 and 16, respectively. PAMAM conjugated chitosan derivatives, dsCS-PAM and CS-PAM, showed higher in vitro transfection efficiency than unconjugated derivatives dsCS and CS. Approximately 80% of A549 and 293 cells were viable in the presence of up to 100 μg/mL of dsCS-PAM. The results of this study demonstrate that dsCS-PAM has the potential to be a safe gene delivery carrier. Open image in new window

To develop a paclitaxel carrier based on chitosan, chitosan oligosaccharide (COS) was chemically modified with bile acid (deoxycholic acid and lithocholic acid) as a hydrophobic group. Paclitaxel was loaded in bile acid conjugated chitosan oligosaccharide (CBs) nanoparticles by a dialysis method. We confirmed that the paclitaxel-loaded COS (CBs-Tx) nanoparticles could be successfully prepared with a yield of 80%–90% and paclitaxel encapsulation of 54%–70%. The size of CB nanoparticles was in the range of 200–300 nm, and it increased to 300–400 nm after paclitaxel loading with the narrow size distribution maintained. Paclitaxel-loaded CBs (CBs-Tx) nanoparticles showed remarkably high anticancer activity compared with paclitaxel in cremophore EL (CrEL)-ethanol against B16F10 cells. The antitumor efficacy in vivo was shown with significant inhibition of the tumor growth in both paclitaxel-treated groups. The effect on tumor size by the paclitaxel in the CrEL-ethanol formulation appeared to be slightly larger than that in CBs-Tx. The decrease in cytotoxicity and the increase in antitumor activity may lead to the improvement in the therapeutic index in clinical use compared to commercial paclitaxel. The efficacy of CBs-Tx nanoparticles suggests that bile acid as a hydrophobic group may have a potential application of effectively loading hydrophobic drugs such as paclitaxel.

In this study, polypeptide/polysaccharide graft copolymers pullulan-g-poly(L-lysine) (PULPLL) was prepared through the ring opening polymerization of ɛ-benzoxycarbonyl L-lysine N-carboxyanhydrides (Z-L-lysine NCA) in the presence of pullulan. The PULPLL copolymer nanoparticles, which are prepared by the diafiltration method, were investigated by using Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance spectra (1H NMR), dynamic light scattering (DLS), transmission electron microscope (TEM), and fluorescence spectroscopy. The PULPLL copolymers formed self-aggregated nanoparticles in the aqueous milieu. The physicochemical characterization revealed that the nanoparticle size ranged between 60 and 500 nanometers, and the critical aggregation concentration (CAC) is 0.001∼0.1 g/L, depending on the degree of substitution. With negligible cytotoxicity and higher transfection efficiency, PULPLL nanoparticles may be safe gene carriers.

：The silica-silica interaction parameter (α F ) of the silane treated silica filled natural rubber (NR) compoundwas investigated. As silane (TESPT) concentration increased from 2 to 12% (2, 4, 6, 8, 10, 12%), the α F value increasedat the same silica concentration (10, 20, 30, and 40 phr). It seemed the sulfur atoms in TESPT acted as a crosslinking agent in the compound. As silica concentration increased from 10 to 40 phr, the α F value increased at the same silaneconcentration due to increased silica-silica interaction. Keywords ：α F (measure of the in-rubber structure of the filler), silica / silane, silica structure, Wolff's theory, naturalrubber(NR). † 대표저자 E-mail: kkim@dongahtire.co.kr Ⅰ. 서 론 충전제 입자간 상호관계를 관찰하기 위해서는 충전제 입자간 상호작용 계수 (α F ), 1,2 Payne effect 3,4 를 측정하는 방법 등 여러 가지가 있다. Wolff는 충전제 로딩량과 토크 상승값 (T max-min )의 함수관계에서 나타나는 기울기를 α F 로 정의하였고 입자가 충전된 복합소재와 비충전된 복합소재의 토크 상승값을 이용하여 측정하였으며 카본블랙과 실리카의 α F 를 비교하였다. 1,2 한편 Payne은 입자간 관계를 strain sweep으로 표현하였는데 입자간 상호작용은 입자들의 percolation point 이상에서 관찰된다. Wolff의 방법은 컴파운드의 토크 변화를 관찰하여 측정하는 것이기 때문에 입자간 상호작용 뿐만 아니라 컴파운드 내의 3차원적 사슬구조 (3-dimensional network)의 증가를 관찰할 수 있는 이점이 있다.

：The silica-silica interaction parameter (α F ) of the silane treated silica filled natural rubber (NR) compoundwas investigated. The measured α F values using mass fraction method following Wolff's theory were compared with volumefraction method. As silica concentration increased, the α F value increased for both methods. The value of α F expressedas volume fraction was higher than that of mass fraction, which resulted in large gaps between α F values. The effect ofaccelerator (MBT) concentration on α F values was compared. Keywords ：α F (measure of the in-rubber structure of the filler), silica / silane, silica structure, Wolff's theory, naturalrubber(NR). † 대표저자 E-mail: kkim@dongahtire.co.kr Ⅰ. 서 론 표면이 hydroxyl 그룹으로 이루어져 있는 실리카는 실란과 함께 고무복합소재에 첨가되었을 시 고무사슬과의 3차원적 사슬구조를 형성한다. 따라서, 카본블랙을 첨가했을 시 보다 회전저항력(rolling resistance) 및 노면접지력(traction) 등에서 우수한 물성들을 보인다. 따라서 실리카는 연비 향상과 눈이나 비가 왔을 시 노면접착력이 우수한 성능이 요구되는 타이어의 tread compound 제조에 사용되고 있다. 1 그 동안 실리카의 보강효과, 2 실리카-실란의 반응

To develop hyaluronic acid (HA)-based anticancer agent carrier, hyaluronic acid was chemically modified with the hydrophobic group of deoxycholic acid(DA). The physicochemical properties of the deoxycholic acid-conjugated HA (HADA) were investigated by using 1 H NMR, FTIR, spectrophotometer and TEM. Paclitaxel (Tx)-loaded HADA nanoparticles were prepared by a dialysis method. The loading efficiency of drug and drug contents of Tx-loaded HADA nanoparticles (HADA-Tx) were measured by HPLC. The anticancer activity of HADA-Tx was investigated by its cytotoxicity against KB cell in vitro. The HADA-Tx was shown to have the superior potential for the anticancer drug delivery.

Doxorubicin (DOX)-conjugated poly(DL-lactide-co-glycolide)(PLGA) was synthesized and nanoparticles were prepared without the use of a surfactant. The DOX content in the nanoparticles ranged from 1.2 to 4.75% (w/w). The particle size of the DOX-conjugated PLGA (DOX-LG) nanoparticles increased when a higher molecular weight (M.W.) of polymer was used. TEM revealed the nanoparticles to have spherical shapes with a size of approximately 100∼200 nm. The drug was released continuously from the nanoparticles over a one month period. In particular, the overall drug release from the nanoparticles prepared with a higher M.W. was significantly faster than that from nanoparticles with a lower M.W. The cytotoxicity test in vitro using CT26 colon carcinoma cells showed that the free DOX had higher cytotoxicity than DOX-LG. These results suggest that DOX was released slowly from nanoparticles and was exposed to the tumor cells. Moreover, DOX-LG might show low cytotoxicity due to these properties of nanoparticles.

Insulin-incorporated nanoparticles were prepared by polyelectrolyte complex formation using low-molecular weight water soluble chitosan (LMWSC). Insulin-incorporated nanoparticles showed spherical shapes with a particle size of approximately 200 nm. The average particle size, drug content and loading efficiency increased with increasing insulin feed. The zeta potential decreased with increasing insulin feed, indicating that the electrostatic interaction increased with increasing insulin feed. At 1H nuclear magnetic resonance (NMR) spectra, insulin and LMWSC had intrinsic peaks while the peaks of the nanoparticles were similar to LMWSC itself at D2O. However, the specific peaks for insulin appeared as a result of the breakdown of nanoparticles using DCl. When polyelectrolyte complex had dissociated, fluorescein isothiocyanate (FITC)-labeled insulin in the nanoparticles showed similar UV absorption peaks to FITC-labeled insulin only. At the release study, insulin was released continuously from the nanoparticles over 120 h at all formulations. Higher insulin contents induced a decrease in the rate of insulin released from nanoparticles. Consequently, LMWSC and insulin successively formed polyelectrolyte complexes as a nanocarriers and LMWSC can be considered a good candidate for insulin delivery. Open image in new window

In this study, methotrexate (MTX)-encapsulated polymeric micelles using methoxy poly(ethylene glycol) (MPEG)-grafted chitosan (ChitoPEG) copolymer were prepared. The MTX-incorporated polymeric micelles of ChitoPEG copolymer has a particle size of around 50-100 nm. In 1H nuclear magnetic resonance (NMR) study, the specific peaks of MTX disappeared in heavy water (D2O) and only the specific peak of MPEG was observed, while all of the peaks were confirmed in dimethyl sulfoxide (DMSO). These results indicated that MTX was complexed with chitosan and then formed an ion complex inner-core of the polymeric micelle in an aqueous environment. The drug contents of the polymeric micelle were around 4∼12% and the loading efficiency of MTX in the polymeric micelles was higher than 60% (w/w) for all of the formulations. The cytotoxicity of MTX and MTX-incorporated polymeric micelle against CT26 tumor cells was not significantly changed.

Noble thermosensitive nanoparticles, based on a PNIPAAm-co-AA core and a chitosan shell structure, were designed and synthesized for the controlled release of the loaded drug. PNIPAAm nanoparticles containing a carboxylic group on their surface were synthesized using emulsion polymerization. The carboxylic groups were conjugated with the amino group of a low molecular weight, water soluble chitosan. The particle size of the synthesized nanoparticles was decreased from 380 to 25 nm as the temperature of the dispersed medium was increased. Chitosan-conjugated nanoparticles with 2∼5 wt% MBA, a crosslinking monomer, induced a stable aqueous dispersion at a concentration of 1 mg/1 mL. The chitosan-conjugated nanoparticles showed thermosensitive behaviors such as LCST and size shrinkage that were affected by the PNIPAAm core and induced some particle aggregation around LCST, which was not shown in the NIPAAm-co-AA nanoparticles. These chitosan-conjugated nanoparticles are also expected to be more biocompatible than the PNIPAAm core itself through the chitosan shell structures.

In this study, we prepared all-trans retinoic acid (ATRA)-encapsulated, surfactant-free, PLGA nanoparticles. The nanoparticles were formed by nanoprecipitation process, after which the solvent was removed by solvent evaporation or dialysis method. When a nanoparticle was prepared by the nanoprecipitation - solvent evaporation method, the nanoparticles were bigger than the nanoparticles of the nanoprecipitation - dialysis method, despite the higher although loading efficiency. Nanoparticles from the nanoprecipitation - dialysis method were smaller than 200 nm in diameter, while the loading efficiency was not significantly changed. Especially, nanoparticles prepared from DMAc, 1,4-dioxane, and DMF had a diameter of less than 100 nm. In the transmission electron microscopy (TEM) observations, all of the nanoparticles showed spherical shapes. The loading efficiency of ATRA was higher than 90 % (w/w) at all formulations with exception of THF. The drug content was increased with increasing drugfeeding amount while the loading efficiency was decreased. In the drug release study, an initial burst was observed for 2∼6 days according to the variations of the formulation, after which the drug was continuously released over one month. Nanoparticles from the nanoprecipitation - dialysis method showed faster drug release than those from the nanoprecipitation — solvent evaporation method. The decreased drug release kinetics was observed at lower drug contents. In the tumor cell cytotoxicity test, ATRA-encapsulated, surfactant-free, PLGA nanoparticles exhibited similar cytotoxicity with that of ATRA itself.

This study is performed to assess the preparation and characterization of lactic acid bacteria (Sterpoccoccus thermophilus) loaded with alginate microsphere using alginate and chitosan for the efficient delivery of lactic acid bacteria to large intestine. Size and morphology of alginate microsphere were confirmed with spherical shape by scanning electronic microscope (SEM). Biodegradation study of alginate was investigated at different buffer solutions (pH 1.2 and 7.4). This result showed that alginate microsphere did not degrade at pH 1.2 buffer solution but it`s degradation occurred from first day at pH 7.4 buffer solution. Survivability test of lactic acid bacteria in alginate microsphere showed that it was keeping activity of lactic acid bacteria by chroma meter. Therefore, the introduction of alginate microsphere might be a potential system to efficiently delivery lactic acid to large intestine.

Thermosensitive nanoparticles were prepared via the self-assembly of two different poly(e-caprolactone)-based block copolymers of poly(N-isopropylacrylamide)-b-poly(e-caprolactone) (PNPCL) and poly(ethylene glycol)-b-poly(e-caprolactone) (PEGCL). The self-aggregation and thermosensitive behaviors of the mixed nanoparticles were investigated using1H-NMR, turbidimetry, differential scanning microcalorimetry (micro-DSC), dynamic light scattering (DLS), and fluorescence spectroscopy. The copolymer mixtures (mixed nanoparticles, M1-M5, with different PNPCL content) formed nano-sized self-aggregates in an aqueous environment via the intra- and/ or intermolecular association of hydrophobic PCL chains. The microscopic investigation of the mixed nanoparticles showed that the critical aggregation concentration (cac), the partition equilibrium constants (Kv) of pyrene, and the aggregation number of PCL chains per one hydrophobic microdomain varied in accordance with the compositions of the mixed nanoparticles. Furthermore, the PNPCL harboring mixed nanoparticles evidenced phase transition behavior, originated by coil to the globule transition of PNiPAAm block upon heating, thereby resulting in the turbidity change, endothermic heat exchange, and particle size reduction upon heating. The drug release tests showed that the formation of the thermosensitive hydrogel layer enhanced the sustained drug release patterns by functioning as an additional diffusion barrier.

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.

Diblock copolymers with different poly(e-caprolactone) (PCL) block lengths were synthesized by ring-opening polymerization of e-caprolactone in the presence of monomethoxy poly(ethylene glycol) (mPEG-OH, MW 2000) as initiator. The self-aggregation behaviors and microscopic characteristics of the diblock copolymer self-aggregates, prepared by the diafiltration method, were investigated by using 1H NMR, dynamic light scattering (DLS), and fluorescence spectroscopy. The PEG–PCL block copolymers formed the self-aggregate in an aqueous environment by intra- and/or intermolecular association between hydrophobic PCL chains. The critical aggregation concentrations of the block copolymer self-aggregate became lower with increasing hydrophobic PCL block length. On the other hand, reverse trends of mean hydrodynamic diameters were measured by DLS owing to the increasing bulkiness of the hydrophobic chains and hydrophobic interaction between the PCL microdomains. The partition equilibrium constants (Kv) of pyrene, measured by fluorescence spectroscopy, revealed that the inner core hydrophobicity of the nanoparticles increased with increasing PCL chain length. The aggregation number of PCL chain per one hydrophobic microdomain, investigated by the fluorescence quenching method using cetylpyridinium chloride as a quencher, revealed that 4–20 block copolymer chains were needed to form a hydrophobic microdomain, depending on PCL block length. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 99: 3520–3527, 2006

Diblock copolymers with different poly(e-caprolactone) (PCL) block lengths were synthesized by ringopening polymerization of e-caprolactone in the presence of monomethoxy poly(ethylene glycol) (mPEG-OH, MW 2000) as initiator. The self-aggregation behaviors of the diblock copolymer nanoparticle, prepared by the diafiltration method, were investigated by using 1 H NMR, dynamic light scattering (DLS), and fluorescence spectroscopy. The PEG-PCL block copolymers formed the nano-sized self-aggregate in an aqueous environment by intrsa- and/or intermolecular association between hydrophobic PCL chains. The critical aggregation concentrations (cac) of the block copolymer self-aggregate became lower with increasing hydrophobic PCL block length. On the other hand, reverse trends of mean hydrodynamic diameters were measured by DLS owing to the increasing bulkiness of the hydrophobic chains and hydrophobic interaction between the PCL microdomains. The hydrodynamic diameters of the block copolymer nanoparticles, measured by DLS, were in the range of 65-270 nm. Furthermore, the size of the nanoparticles was scarcely affected by the concentration of the block copolymers in the range of 0.125-5 mg/mL owing to the negligible interparticular aggregation between the self-aggregated nanoparticles. Considered with the fairly low cac and nanoparticle stability, the PEG-PCL nanoparticles can be considered a potential candidate for biomedical applications such as drug carrier or imaging agent.

Melt blending of Bisphenol A polycarbonate(PC) and poly(trimethylene terephthalate)(PTT) was carried out over the entire composition range. The mixing time was varied up to 90 min. The resulting samples were analyzed by FT-IR, DSC, XRD, DMTA,1H NMR, and SEM. The process of transesterification between the two polymers and their resulting compatibilization were observed. The behaviors of the PTT-rich and PC-rich blends were different and an equilibrium was found to exist. Peculiar behavior, which was different from that of the PTT-rich and PC-rich blends, was exhibited by the 50/50(PTT/PC) blend.

To prepare chitosan-based polymeric amphiphiles that can form nanosized core-shell structures (nanoparticles) in aqueous milieu, chitosan oligosaccharides (COSs) were modified chemically with hydrophobic cholesterol groups. The physicochemical properties of the hydrophobized COSs (COSCs) were investigated by using dynamic light scattering and fluorescence spectroscopy. The feasibility of applying the COSCs to biomedical applications was investigated by introducing them into a gene delivery system. The COSCs formed nanosized self-aggregates in aqueous environments. Furthermore, the physicochemical properties of the COSC nanoparticles were closely related to the molecular weights of the COSs and the number of hydrophobic groups per COS chain. The critical raggregation concentration values decreased upon increasing the hydrophobicity of the COSCs. The COSCs efficiently rcondensed plasmid DNA into nanosized ion-complexes, in contrast to the effect of the unmodified COSs. An investigation of gene condensation, performed using a gel retardation assay, revealed that COS6(M n = 6,040 Da) containing 5% of cholesteryl chloroformate (COS6C5) formed a stable DNA complex at a COS6C5/DNA weight ratio of 2. In contrast, COS6, the unmodified COS, failed to form a stable COS/DNA complex even at an elevated weight ratio of 8. Furthermore, the COS6C5/DNA complex enhanced thein vitro transfection efficiency on Human embryonic kidney 293 cells by over 100 and 3 times those of COS6 and poly(L-lysine), respectively. Therefore, hydrophobized chitosan oligosaccharide can be considered as an efficient gene carrier for gene delivery systems.

The low molecular water-soluble chitosan nanoparticles (LMWSC-NPs) were prepared, which was modified with hydrophilic and hydrophobic moieties to evaluate the potential for pharmaceutics application. The synthesis of LMWSC-NPs was identified by FT-IR and 'H-NMR spectra. Also, we measured the photon correlation spectroscopy (PCS), transmission electron microscope (TEM) and atomic force microscope (AFM) to investigate the characteristics and morphology of the LMWSC-NPs. At the PCS measurement, the more increase the number of substitutive group, the more decrease the positive charge of LMWSC-NP surface. From the results of TEM and AFM, spherical morphologies were observed, and their sizes were 30-150 nm. Resultantly, LMWSC-NPs prepared in this experiment will be expected as a suitable device for the drug targeting system.

Surfactant-free nanoparticles of poly(DL-lactide-co-glycolide) (PLGA) nanoparticles were prepared with or without poly(L-lactide)-poly(ethylene oxide) (LE) diblock copolymer (abbreviated as PLGA/LE and PLGA nanoparticles) by dialysis method. LE diblock copolymer was used to make PLGA nanoparticles to alternate conventional surfactant. The size of PLGA and PLGA/LE nanoparticles was 295.3 ± 171.3 and 307.6 ± 27.2 nm, respectively, suggesting LE diblock copolymer might be coated onto the surface of nanoparticles. Observation of scanning electron microscope (SEM) showed that PLGA/LE nanoparticles have spherical shapes ranging ∼ 200–500 nm. In 1H-NMR study, characteristic peaks of the methyl protons of PLGA disappeared in D2O, whereas characteristic peaks of the methyl proton of both PEG and PLGA were shown in both CDCl3 and D2O, indicating that LE diblock copolymer coated on the surface of the PLGA nanoparticles. The higher the initial content of drug, the higher the drug contents and the lower the loading efficiency. PLGA/LE nanoparticles at higher drug contents resulted in slower adriamycin·HCl (ADR) release rate than that of lower drug contents. Also, slower release rate of ADR was achieved by entrapped into the PLGA/LE nanoparticles, whereas LE polymeric micelles showed rapid ADR release. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 1116–1123, 2003

Seong-Cheol Park,* Joung-Pyo Nam,* Young-Min Kim,* Jun-Ho Kim, Jae-Woon Nah, Mi-Kyeong Jang Biomedical Polymer Laboratory, Department of Polymer Science and Engineering, Sunchon National University, Suncheon, Republic of Korea *These authors contributed equally to this work Abstract: To generate a good carrier for gene transfection, O-carboxymethyl chitosan-graft-branched polyethylenimine (OCMPEI) copolymers were synthesized by increasing the weight percentage of branched polyethylenimine conjugated to the carboxyl groups of O-carboxymethyl chitosan. These spherical polyplexes with plasmid deoxyribonucleic acid (pDNA) or small interfering ribonucleic acid (siRNA) had diameters of ~200–300 nm or ~10–25 nm, respectively, and displayed significant transfection efficiency in normal and tumor cells. In particular, expression of green fluorescent protein (GFP) following pDNA transfection was effectively suppressed by delivery of GFP-specific siRNA with the same copolymer. The optimized copolymer and polyplexes were nontoxic in vitro and in vivo. The use of endocytosis inhibitors to investigate the mechanisms of transfection of the polyplexes suggested the involvement of macropinocytosis. An in vivo study in mice showed excellent GFP expression in the lung, kidney, and liver. The results demonstrated that the OCMPEI copolymer prepared in this study is a promising carrier for in vitro and in vivo gene delivery applications. Keywords: chitosan, branched polyethylenimine, gene transfection, cytotoxicity, endocytosis

In this study, new polysaccharide-based thermo-sensitive polymers were synthesized and their thermo-sensitive sol-gel transition properties were evaluated. Glycol chitin structures were successfully introduced by N-acetylation reaction of glycol chitosan. The aqueous solutions of glycol chitins demonstrated unique thermo-sensitive sol-gel transition behaviors around 37 C. Their sol-gel transition properties were observed at a relatively lower concentration range (3~16 wt%) compared to those of typical synthetic polymer based systems and efficiently modulated by varying molecular weight, DA, and concentration. Based on their thermo-sensitivity, low cyto-toxicity, and high gel stability, the glycol chitin polymers could be utilized for various biomedical applications, such as drug delivery, tissue engineering, and 3D cell culture.