• Journal of Pharmaceutical Investigation
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• 제38권4호
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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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• 제13권1호
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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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• 제9권4호
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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.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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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)

• 대한비뇨기종양학회지
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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.

• 대한의용생체공학회:학술대회논문집
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• 대한의용생체공학회 1996년도 추계학술대회
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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.

• 대한화학회지
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• 제47권3호
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• pp.257-264
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• 2003

본 연구에서는 외부온열 온도$(~40^{\circ}C)$에서 항암약물(doxorubicin)이 방출되는 온도민감성 리포좀에 대하여 연구하였다. 온도민감성 리포좀은 외부온열온도에서 하한임계용액온도의 성질을 나타내는 N-isopropylacrylamide (NIP-AAm)와 Acrylamide(AAm)의 합성고분자에 의하여 변형되었다. 변형된 리포좀으로부터 약물(doxorubicin)의 방출은 온도와 시간의 변화에 따라서 형광강도를 측정하여 결정하였다. Poly(NIPAAm-co-AAm) copolymer에 의하여 변형된 리포좀으로부터 약물(doxorubicin)의 방출은 Poly(NIPAAm-co-AAm) copolymer가 온열온도 범위$(~40{\pm}2^{\circ}C)$에서 적절한 전이를 나타내기 때문에 증가하였다. 또한, 리포좀으로부터 약물의 방출은 5분 이내에 완료되었고, 변형된 리포좀의 크기는 120~170 nm 이었다. 본 연구에서는 온도에 의하여 제어 할 수 있는 온도민감성 리포좀을 제조하였다. 이것은 온도 제어에 따른 종양 표적화에 대한 약물전달시스템에서 활용 될 수 있을 것이다.

• 한국고분자학회:학술대회논문집
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• 한국고분자학회 2006년도 IUPAC International Symposium on Advanced Polymers for Emerging Technologies
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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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• 제16권8호
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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.

• 폴리머
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• 제36권2호
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• pp.223-228
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• 2012

온도와 pH 민감성을 갖는 그래프트 공중합체[Pluronic-$g$-poly(NIPAAm-$co$-MMA), Polymer A]와 [Pluronic-$g$-poly(NIPAAm-$co$-MAA), Polymer C]는 $t$-butylperoxybenzoate를 이용하여 Pluronic 공중합체의 주사슬에 $N$-isopropylacrylamide (NIPAAm)/$N,N$-diethylaminoethylmethacrylate (DEAEMA)와 $N$-isopropylacrylamide(NIPAAm)/methacrylic acid (MAA)를 각각 합성하였다. 그래프트 공중합체는 $^1H$ NMR과 젤 투과 크로마토그래피를 통해 공중합체의 화학적 구조와 분자량을 측정하였다. 그래프트 공중합체의 수용액 상에서의 특성은 다른 온도와 pH 조건에서 자외 및 가시선 분광 분석법, 접촉각 측정과 동적 광산란으로 측정되었다. 그래프트 공중합체는 수용액상에서 온도와 pH에 따라 민감한 상 변화를 보인다. 이는 DEAEMA 단량체의 아민 그룹과 MAA 단량체의 카복실 그룹은 각각 Polymer A와 Polymer C에서 하한임계용액온도에 큰 영향을 미친다고 제시한다. 그래프트 공중합체는 온도와 pH 변화에 관련된 다양한 약물 전달과 분자 스위치 적용에 사용될 수 있다.