• Macromolecular Research
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• v.13 no.1
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• pp.54-61
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• 2005

We prepared temperature-sensitive liposomes (TS-liposomes) modified with a thermo sensitive polymer, such as poly(N-isopropylacrylamide) (PNIPAAm), to increase the degree of drug release from liposomes at the hyperthermic temperature. A PNIPAAm hydrogel containing TS-Iiposomes was also prepared to obtain a hydrogel complex at body temperature. In addition, a depot system for local drug delivery using the polymer hydrogel was developed to enhance therapeutic efficacy and prevent severe side effects in the whole body. The PNIPAAm-mod­ified TS-liposome was fixed into the PNIPAAm hydrogel having a high temperature-sensitivity. The release behavior of calcein, a model drug, from TS-liposomes in the PNIPAAm hydrogel was then initiated by external hyperthermia; the results indicated that sustained release as a function of temperature and time was caused by the thermosensitivity of the liposome surface and diffusion of the drug into the PNIPAAm hydrogel. Our results indicated that TS-liposomes in a PNIPAAm hydrogel represented a plausible system for local drug delivery.

• Polymer(Korea)
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• v.38 no.5
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• pp.626-631
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• 2014

Water purification requires a large amount of energy that can cause pollution problems. For this reason, forward osmosis (FO) has attracted intense interest that required a relatively low amount of energy for water purification. The forward osmosis has a serious problem that it needs drawing agents creating osmotic pressure to extract water from contaminated water. In this study, a copolymer of zwitterionic moiety and an interpenetrating polymer network (IPN) hydrogel based on thermo-responsive polymer hydrogel, poly(N-isopropylacrylamide) (PNIPAM) were prepared and attached on FO membranes, which successfully played the role of drawing agents. In the copolymer hydrogel, its swelling ratio was improved, but thermo-sensitivity was decreased. The swelling ratio and thermo-sensitivity of IPN hydrogel was lowered. We could confirm that swelling ratio is related to osmotic pressure.

• The Korean Journal of Urological Oncology
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• 제15권3호
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• pp.178-186
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• 2017

Purpose: Poloxamer 407 (P407) thermo-sensitive hydrogel formulations were developed to enhance the retention time in the urinary bladder after intravesical instillation. Materials and Methods: P407 hydrogels (P407Gels) containing 0.2 w/w% fluorescein isothiocyanate dextran (FD, MW 4 kDa) as a fluorescent probe were prepared by the cold method with different concentrations of the polymer (20, 25, and 30 w/w%). The gel-forming capacities were characterized in terms of gelation temperature (G-Temp), gelation time (G-Time), and gel duration (G-Dur). Homogenous dispersion of the probe throughout the hydrogel was observed by using fluorescence microscopy. The in vitro bladder simulation model was established to evaluate the retention and drug release properties. P407Gels in the solution state were administered to nude mice via urinary instillation, and the in vivo retention behavior of P407Gels was visualized by using an in vivo imaging system (IVIS). Results: P407Gels showed a thermo-reversible phase transition at $4^{\circ}C$ (refrigerated; sol) and $37^{\circ}C$ (body temperature; gel). The G-Temp, G-Time, and G-Dur of FD-free P407Gels were approximately $10^{\circ}C-20^{\circ}C$, 12-30 seconds, and 12-35 hours, respectively, and were not altered by the addition of FD. Fluorescence imaging showed that FD was spread homogenously in the gelled P407 solution. In a bladder simulation model, even after repeated periodic filling-emptying cycles, the hydrogel formulation displayed excellent retention with continuous release of the probe over 8 hours. The FD release from P407Gels and the erosion of the gel, both of which followed zero-order kinetics, had a linear relationship ($r^2=0.988$). IVIS demonstrated that the intravesical retention time of P407Gels was over 4 hours, which was longer than that of the FD solution (<1 hour), even though periodic urination occurred in the mice. Conclusions: FD release from P407Gels was erosion-controlled. P407Gels represent a promising system to enhance intravesical retention with extended drug delivery.

• 한국생물공학회:학술대회논문집
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• 2000.04a
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• pp.562-565
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• 2000

pH- and thermo-sensitive hydrogels containing maleilated chitosan(MC) and N-isopropylacrylamide(NIPAAm) were prepared and characterized for their swelling behavior, biodegradability and drug release profiles. The hydrogels exhibited a typical pH-sensitivity due to the carboxylic acid groups of maleilated chitosan. The change of ratio of NIPAAm to MC in weight did not affect on either lower critical solution temperature(LCST) or EWC significantly. The pH sensitivity of the hydrogel, however, depended on the amounts of carboxylic acid groups of MC. MC was degradable up to 80% weight reduction in 2 hours. The in vitro drug relase profiles were established both in buffer solution pH 1.4 and pH 7.4. Only a negligible amount of indomethacin was released at pH 1.4 in 6 hours, while at pH 7.4 more than 90% of the total drug in the hydrogel was gradually released over ca. 5 hours.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.49-54
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• 2014

Background: Hydrogels are a class of polymers that can absorb water or biological fluids and swell to several times their dry volume, dependent on changes in the external environment. In recent years, hydrogels and hydrogel nanocomposites have found a variety of biomedical applications, including drug delivery and cancer treatment. The incorporation of nanoparticulates into a hydrogel matrix can result in unique material characteristics such as enhanced mechanical properties, swelling response, and capability of remote controlled actuation. Materials and Methods: In this work, synthesis of hydrogel nanocomposites containing magnetic nanoparticles are studied. At first, magnetic nanoparticles ($Fe_3O_4$) with an average size 10 nm were prepared. At second approach, thermo and pH-sensitive poly (N-isopropylacrylamide -co-methacrylic acid-co-vinyl pyrrolidone) (NIPAAm-MAA-VP) were prepared. Swelling behavior of co-polymer was studied in buffer solutions with different pH values (pH=5.8, pH=7.4) at $37^{\circ}C$. Magnetic iron oxide nanoparticles ($Fe_3O_4$) and doxorubicin were incorporated into copolymer and drug loading was studied. The release of drug, carried out at different pH and temperatures. Finally, chemical composition, magnetic properties and morphology of doxorubicin-loaded magnetic hydrogel nanocomposites were analyzed by FT- IR, vibrating sample magnetometry (VSM), scanning electron microscopy (SEM). Results: The results indicated that drug loading efficiency was increased by increasing the drug ratio to polymer. Doxorubicin was released more at $40^{\circ}C$ and in acidic pH compared to that $37^{\circ}C$ and basic pH. Conclusions: This study suggested that the poly (NIPAAm-MAA-VP) magnetic hydrogel nanocomposite could be an effective carrier for targeting drug delivery systems of anti-cancer drugs due to its temperature sensitive properties.

• Polymer(Korea)
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• v.30 no.3
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• pp.196-201
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• 2006

Poly (ethylene glycol)-based diblock and triblock thermo- sensitive polyester copolymers were investigated for application on tissue engineering and injectable biomaterials in drug delivery system due to their nontoxicity, biocompatibility and biodegradability. We synthesized the diblock copolymers consisting of methoxy poly (ethylene glycol) (MPEG) (Mn=750 g/mole) and poly $(\varepsilon-caprolactone)$ (PCL) by ring opening polymerization of $\varepsilon-CL$ with MPEG as an initiator in the presence of HCl $Et_2O$. The effect of diblock copolymers on in vivo osteogenic differentiation of rat bone marrow stromal cells (BMSCS) with and without the presence of osteogenic supplements (dexamethasone) was investigated. Thin sections were cut from paraffin embedded tissues and histological sections were stained by H&E, von Kossa, and immunohistochemical staining for osteocalcin. In conclusion, dexamethasone containing thermo- sensitive hydrogel might be improved osteogenic differentiation of BMSCs. We expect the osteoinduction effect to be excellent when it uses stem cell or other osteogenic materials.

• Macromolecular Research
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• v.17 no.12
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• pp.1025-1031
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• 2009

Several kinds of biodegradable hydrogels were prepared via in situ photopolymerization of Pluronic F127/poly($\varepsilon$-caprolactone) macromer and acrylic acid (AA) comonomer in aqueous medium. The swelling kinetics measurements showed that the resultant hydrogels exhibited both thermo- and pH-sensitive behaviors, and that this stimuli-responsiveness underwent a fast reversible process. With increasing pH of the local buffer solutions, the pH sensitivity of the hydrogels was increased, while the temperature sensitivity was decreased. In vitro hydrolytic degradation in the buffer solution (pH 7.4, $37^{\circ}C$), the degradation rate of the hydrogels was greatly improved due to the introduction of the AA comonomer. The in vitro release profiles of bovine serum albumin (BSA) in-situ embedded into the hydrogels were also investigated: the release mechanism of BSA based on the Peppas equation was followed Case II diffusion. Such biodegradable dual-sensitive hydrogel materials may have more advantages as a potentially interesting platform for smart drug delivery carriers and tissue engineering scaffolds.

• Polymer(Korea)
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• v.36 no.2
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• pp.223-228
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• 2012

Temperature and pH sensitive graft copolymers [Pluronic-$g$-poly(NIPAAm-$co$-MMA), Polymer A] and [Pluronic-$g$-poly( NIPAAm-$co$-MAA), Polymer C] were synthesized by macro radical graft polymerization with $N$-isopropylacrylamide (NIPAAM)/$N,N$-diethylaminoethylmethacrylate (DEAEMA) and $N$-isopropylacrylamide (NIPAAm)/methacrylic acid (MAA) based on Pluronic, respectively. The chemical structure and molecular weight of the graft copolymers was characterized by $^1H$ NMR and gel permeation chromatography. The aqueous solution properties of graft copolymers were measured using a UV-visible spectrophotometer, contact angle and dynamic light scattering equipment with different temperature and pH conditions. The obtained graft copolymers showed a very sensitive phase transition in response to temperature and pH in aqueous media which suggested that the amine group of DEAEMA segment and carboxylic group of MAA had a great influence on the lower critical solution temperatures (LCST) in Polymer A and C, respectively. The graft copolymers can be utilized for drug delivery system and molecular switching applications where responses to temperature and pH changes are relevant.