• Journal of Pharmaceutical Investigation
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• v.38 no.4
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• pp.229-234
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• 2008

In the present study, chitosan-glycerophosphate sodium salt solution as a thermosensitive system (TSS) was used to formulate a temperature-sensitive drug delivery system (TSDDS) containing acetaminophen (AAP). The optimized TSS was prepared by measuring gelation temperature, gelation time and rheological properties of TSS. The optimized gelation temperature and time of TSS were $36^{\circ}C$ and 100 seconds, respectively. The viscosity of TSS was also suitable for maintaining gel structure at $37.2^{\circ}C$. The release profiles of TSDDS in PBS/pH 7.4 with various apparatuses and mass loss of TSDDS were investigated. The time required to release 50% of AAP from TSDDS ($t_{50%}$) was 120 min with the formation of pore on the surfaces, which was 2 times longer than that from AAP-chitosan gel. In addition, TSDDS was degraded approximately 80% within 4 hr and then degraded slowly for 20 hrs. In conclusion, AAP-TSS (TSDDS) formulated in this study might be suitable for some specific uses such as subcutaneous injection and rectal formulation.

• 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.

• Carbon letters
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• v.9 no.4
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• pp.283-288
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• 2008

The composites of temperature-sensitive hydrogel and activated carbons were prepared in order to improve both the mechanical strength of hydrogel matrix and the loading capacity of drug in a hydrogel drug delivery system. The swelling of composite hydrogel was varied depending on the temperature. Both the swelling and the release behavior of the composite hydrogel were varied depending on the kind of activated carbon. The release behavior showed the high efficiency which is important for practical applications.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.425.2-425.2
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• 2002

The purpose of this study was to prepare thermo-sensitive solid-lipid nanoparticles (SLNs) with a lipid melted at human body temperature and to evaluate physicochemical properties of SLNs containing retinol. anti-wrinkle agent. as a model drug. SLNs were prepared using a high pressure homogenizing method. The SLNs were composed of retinol as a model drug. thermo-sensitive lipid (DS-CBS) as a lipid core. and egg phosphatidylcholine and Tween 80 as surfactants. Manufacturing variables such as homogenization pressure. (omitted)

• 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.

• Proceedings of the KOSOMBE Conference
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• v.1996 no.11
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• pp.281-285
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• 1996

Pulsatile swelling behaviors and their application to drug delivery system were studied by using interpenetrating polymer networks(IPN) hydrogels constructed with poly(vinyl alcohol) and poly(acrylic acid). The PVA/PAAc IPNs hydrogels were symthesized by UV irradiation tallowed by repetitive freezing and thawing method. These hydrogels showed pH and temperature sensitive swelling behaviors. From the release experiment, the release amount of model drug incorporated into these hydrogels showed pulsatile patterns. Permeability coefficients obtained by various solutes differed in response to changes of permeation conditions.

• Journal of the Korean Chemical Society
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• v.47 no.3
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• pp.257-264
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• 2003

This study has investigated the temperature-sensitive liposomes, which release anticancer drug(doxorubicin) at the hyperthermia temperature$(~40^{\circ}C)$. The temperature-sensitive liposomes were modified with a copolymers of N-isopropylacrylamide(NIPAAm) and acrylamide(AAm), which exhibit a lower critical solution temperature (LCST) at the hyperthermia temperature. The release of doxorubicin from the modified liposomes was determined by measuring the fluorescence intensity with changing temperature and time. The release of doxorubicin from liposomes modified with poly(NIPAAm-co-AAm) copolymer was increased significantly, because poly(NIPAAm-co-AAm) could undergo the conformational transition in the narrow hyperthermia temperature region$(~40{\pm}2^{\circ}C)$. Moreover, we observed that doxorubicin released from liposomes within 5 minutes, and the size of modified liposomes was 120~170 nm. In this study, we have prepared temperature-sensitive liposomes which could be controlled by temperature. They can be applied in the field of a drug delivery system for tumor targeting by temperature control.

• Proceedings of the Polymer Society of Korea Conference
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• 2006.10a
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• pp.263-263
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• 2006

Poly (ethylene glycol)(PEG) - Poly (${\varepsilon}-caprolactone(CL)$) - Poly (D,L lactide(LA) (PCLA-PEG-PCLA) was synthesized by ring-opening polymerization to form temperature sensitive hydrogel triblock copolymer. The triblock copolymer was acrylated by acryloyl chloride. ${\beta}-amino$ ester was used as a pH sensitive moiety, in this study ${\beta}$- amino ester obtained from 1,4-butandiol diacrylate, and 4, 4' trimethylene dipiperidine, it have pKb around 6.6. pH/temperature sensitive penta-block copolymer (PAE-PCL-PEG-PCL-PAE) was synthesized by addition polymerization from acrylated triblock copolymer, 1,4-butandiol diacrylate, and 4, 4' trimethylene dipiperidine. Their physicochemical properties of triblock and penta-block copolymers were characterized by $^1H-NMR$ spectroscopy and gel permeation spectroscopy. Sol-gel phase transition behavior of PAE-PCL-PEG-PCL-PAE block copolymers were investigated by remains stable method. Aqueous media of the penta-block copolymer (at 20 wt%) changed from a sol phase at pH 6.4 and $10^{\circ}C$ to a gel phase at pH 7.4 and $37^{\circ}C$. The sol-gel transition properties of these block copolymers are influenced by the hydrophobic/hydrophilic balance of the copolymers, block length, hydrophobicity, stereo-regularity of the hydrophobic of the block copolymer, and the ionization of the pH function groups in the copolymer depended on the changing of environmental pH, respectively. The degradation and the stabilization at pH 7.4 and $37^{\circ}C$, and the stabilization at pH 6.4 and $10^{\circ}C,\;5^{\circ}C,\;0^{\circ}C$, of the gel were determined. The results of toxicity experiment show that the penta block copolymer can be used for injection drug delivery system. The sol?gel transition of this block copolymer also study by in vitro test ($200{\mu}l$ aqueous solution at 20wt% polymer was injected to mouse). Insulin loading and releasing by in vitro test was investigated, the results showed that insulin can loading easily into polymer matrix and release time is around 14-16days. The PAE-PCL-PEG-PCL-PAE can be used as biomaterial for drug, protein, gene loading and delivery.

• Macromolecular Research
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• v.16 no.8
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• pp.670-675
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• 2008

A series of pH and temperature-responsive (N,N-diethylacrylamide-co-methylacrylic acid) copolymers were synthesized by radical copolymerization and characterized by elemental analysis, Fourier-transform infrared (FT-IR), nuclear magnetic resonance (NMR) $^1H$, $^{13}C$ and LLS. The effects of salt and pH on the phase transition behaviors of the copolymers were investigated by uv. With increasing NaCl concentration, significant salt effects on their phase transition behaviors were observed. UV spectroscopic studies showed that the phase transition became faster with increasing NaCl concentration. In addition, the phase transition behaviors of copolymers were sensitive to pH. The pH and temperature sensitivity of these copolymers would make an interesting drug delivery system.

• 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.