• Macromolecular Research
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• 제14권4호
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• pp.461-465
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• 2006

Two types of injectable system using thermosensitive chitosan (chitosan-g-NIPAAm), hydrogel and microparticles (MPs)-embedded hydrogel were developed as drug carriers for controlled release and their pharmaceutical potentials were investigated. 5-Fluorouracil (5-FU)-loaded, biodegradable PLGA MPs were prepared by a double emulsion method and then simply mixed with an aqueous solution of thermosensitive chitosan at room temperature. All 5-FU release rates from the hydrogel matrix were faster than bovine serum albumin (BSA), possibly due to the difference in the molecular weight of the drugs. The 5-FU release profile from MPs-embedded hydrogel was shown to reduce the burst effect and exhibit nearly zero-order release behavior from the beginning of each initial stage. Thus, these MPs-embedded hydrogels, as well as thermosensitive chitosan hydrogel, have promising potential as an injectable drug carrier for pharmaceutical applications.

• Macromolecular Research
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• 제12권5호
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• pp.507-511
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• 2004

We have developed an injectable thermosensitive hydrogel for local drug delivery to treat cancers clinically. We selected chitosan as a polymer matrix because of its biocompatibility and biodegradability. Glycerol 2-phosphate disodium salt hydrate (${\beta}$-GP) was used to neutralize the chitosan solution to physiological pH. The chitosan solution displayed a sol-gel phase transition in a pH-and temperature-dependent manner and formed an endothermic hydrogel after subcutaneous injection into mouse in the presence of ${\beta}$-GP. Additionally, we evaluated the biodegradation of chitosan hydrogel in mice by measuring the volume of injected chitosan hydrogel after subcutaneous injection. The injected chitosan hydrogel in mice was sected and stained with hematoxylin-eosin reagent for histological observation to confirm biodegradation of the hydrogel by the infiltrated cells. Chitosan hydrogel systems that possess biocompatibility and biodegradability could be promising thermosensitive injectable materials useful as depot systems for local anti-cancer drug delivery.

• 대한화학회지
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• 제56권4호
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• pp.473-477
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• 2012

The novel chitosan-based thermosensitive hydrogels were prepared as control-releasing drug carriers. N-carboxyethyl chitosan (ACS) was synthesized by microwave heating for 1 h through Michael addition of CS to acrylic acid in a grafting yield of 52.97%, which was proved to be a faster and more efficient way than ordinary methods. 5-Fu was modified with formaldehyde to synthesize N,N'-Bis(hydroxymethyl)-5-fluorouracil (5-Fu-OH). Then an esterification was performed using ACS and 5-Fu-OH to give 5-Fu-ACS. The new thermosensitive hydrogels were prepared by adding sodium glycerophosphate to the solution of compounds under a certain constant temperature. Simultaneously, the hydrogels' swelling rate, in vitro drug release rate and thermosensitive were studied, and found that the 5-Fu-ACS composite hydrogel had more excellent releasing effect, higher drug loading and better thermosensitive.

• 한국농업기계학회:학술대회논문집
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• 한국농업기계학회 2017년도 춘계공동학술대회
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• pp.107-107
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• 2017

3D bioprinting is a technology to produce complex tissue constructs through printing living cells with hydrogel in a layer-by-layer process. To produce more stable 3D cell-laden structures, various materials have been developed such as alginate, fibrin and gelatin. However, most of these hydrogels are chemically bound using crosslinkers which can cause some problems in cytotoxicity and cell viability. On the other hand, thermosensitive hydrogels are physically cross-linked by non-covalent interaction without crosslinker, facilitating stable cytotoxicity and cell viability. The examples of currently reported thermosensitive hydrogels are poly(ethylene glycol)/poly(propylene glycol)/poly(ethylene glycol) (PEG-PPG-PEG) and poly(ethylene glycol)/poly(lactic acid-co-glycolic acid) (PEG/PLGA). Chitosan, which have been widely used in tissue engineering due to its biocompatibility and osteoconductivity, can be used as thermosensitive hydrogels. However, despite the many advantages, chitosan hydrogel has not yet been used as a bioink. The purpose of this study was to develop a bioink by chitosan hydrogel for 3D bioprinting and to evaluate the suitability and potential ability of the developed chitosan hydrogel as a bioink. To prepare the chitosan hydrogel solution, ${\beta}-glycerolphosphate$ solution was added to the chitosan solution at the final pH ranged from 6.9 to 7.1. Gelation time decreased exponentially with increasing temperature. Scanning electron microscopy (SEM) image showed that chitosan hydrogel had irregular porous structure. From the water soluble tetrazolium salt (WST) and live and dead assay data, it was proven that there was no significant cytotoxicity and that cells were well dispersed. The chitosan hydrogel was well printed under temperature-controlled condition, and cells were well laden inside gel. The cytotoxicity of laden cells was evaluated by live and dead assay. In conclusion, chitosan bioink can be a candidate for 3D bioprinting.

• 폴리머
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• 제39권3호
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• pp.480-486
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• 2015

조직과 장기 유착은 외과적 수술 후 부작용으로 자주 발생된다. 이러한 조직 유착을 방지하기 위하여 유착부위에 장벽을 형성하여 장기 유착을 방지할 수 있는 온도감응성 하이드로젤 유착방지제를 제조하고자 하였다. 폴록사머, 키토산과 표피성장인자를 가지고 온도감응성 키토산 하이드로젤을 제조하였다. 제조한 키토산 하이드로젤은 인체 내 온도와 유사한 $35^{\circ}C$에서 졸-젤 전이현상을 보였고, 1분 이내에 빠르게 젤화되었다. 키토산 하이드로젤은 표피성장인자를 7일 동안 천천히 방출하였고, 마우스모델에서 평가한 결과 조직 유착 방지를 효과적으로 하는 것을 확인하였다. 온도 감응성과 항균성을 갖는 키토산 하이드로젤이 장기 부착의 증가와 표피성장인자를 천천히 방출하는 유착방지제로서 유용하게 사용될 수 있다.

• Macromolecular Research
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• 제15권7호
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• pp.623-632
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• 2007

Thermosensitive nanoparticles were prepared via the self-assembly of two different $poly({\varepsilon}-caprolactone)$-based block copolymers of poly(N-isopropylacrylamide)-b-$poly({\varepsilon}-caprolactone)$ (PNPCL) and poly(ethylene glycol)-b-$poly({\varepsilon}-caprolactone)$ (PEGCL). The self-aggregation and thermosensitive behaviors of the mixed nanoparticles were investigated using $^1H-NMR$, 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 $(K_v)$ 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.

• Journal of Microbiology and Biotechnology
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• 제34권6호
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• pp.1229-1238
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• 2024

This study aimed to develop and assess a chitosan biomedical antibacterial gel ZincOxide-GrapheneOxide/Chitosan/β-Glycerophosphate (ZnO-GO/CS/β-GP) loaded with nano-zinc oxide (ZnO) and graphene oxide (GO), known for its potent antibacterial properties, biocompatibility, and sustained drug release. ZnO nanoparticles (ZnO-NPs) were modified and integrated with GO sheets to create 1% and 3% ZnO-GO/CS/β-GP thermo-sensitive hydrogels based on ZnO-GO to Chitosan (CS) mass ratio. Gelation time, pH, structural changes, and microscopic morphology were evaluated. The hydrogel's antibacterial efficacy against Porphyromonas gingivalis, biofilm biomass, and metabolic activity was examined alongside its impact (MC3T3-e1). The findings of this study revealed that both hydrogel formulations exhibited temperature sensitivity, maintaining a neutral pH. The ZnO-GO/CS/β-GP formulation effectively inhibited P. gingivalis bacterial activity and biofilm formation, with a 3% ZnO-GO/CS/β-GP antibacterial rate approaching 100%. MC3T3-e1 cells displayed good biocompatibility when cultured in the hydrogel extract.The ZnO-GO/CS/β-GP thermo-sensitive hydrogel demonstrates favorable physical and chemical properties, effectively preventing P. gingivalis biofilm formation. It exhibits promising biocompatibility, suggesting its potential as an adjuvant therapy for managing and preventing peri-implantitis, subject to further clinical investigations.

• 한국막학회:학술대회논문집
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• 한국막학회 1995년도 춘계 총회 및 학술발표회
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• pp.50-51
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• 1995

The swelling behavior of hyddrogels has been interested in many applications of drug carriers. These gels show reversible swelling changes in response to pH, electric currcnt, and temperature. Among others, the temperature-responsive behavior of poly(N-isopropylacrylanxide) (p(NIPAAm)) was studied, because a lower critical solution temperature(LCST) is in the vicinity of 32$\circ$C, and remarkable temperature-response can be obtained. We propose a novel composite membrane, which is appropriate for transporting drug ingredients above the transition temperature. Our object was to design a high permeation system above the shrinking temperature of p(NIPAAm). The membrane was composed of a matrix polymer and thermosensitive p(NIPAAm) hydrogel. The flux pattern of 4-acctamidophen through membrane in response of temperature was opposite to that of p(NIPAAm) membrane.

• Macromolecular Research
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• 제16권6호
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• pp.517-523
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• 2008

A RGD (Arg-Gly-Asp) conjugated chitosan hydrogel was used as a cell-supporting scaffold for articular cartilage regeneration. Thermosensitive chitosan-Pluronic (CP) has potential biomedical applications on account of its biocompatibility and injectability. A RGD-conjugated CP (RGD-CP) copolymer was prepared by coupling the carboxyl group in the peptide with the residual amine group in the CP copolymer. The chemical structure of RGD-CP was characterized by $^1H$ NMR and FT IR. The concentration of conjugated RGD was quantified by amino acid analysis (AAA) and rheology of the RGD-CP hydrogel was investigated. The amount of bound RGD was $0.135{\mu}g$ per 1 mg of CP copolymer. The viscoelastic parameters of RGD-CP hydrogel showed thermo-sensitivity and suitable mechanical strength at body temperature for cell scaffolds (a> 100 kPa storage modulus). The viability of the bovine chondrocyte and the amount of synthesized glycosaminoglycans (GAGs) on the RGD-CP hydrogels were evaluated together with the alginate hydrogels as a control over a 14 day period. Both results showed that the RGD-CP hydrogel was superior to the alginate hydrogel. These results show that conjugating RGD to CP hydro gels improves cell viability and proliferation, including extra cellular matrix (ECM) expression. Therefore, RGD conjugated CP hydrogels are quite suitable for a chondrocyte culture and have potential applications to the tissue engineering of articular cartilage tissue.

• Journal of Microbiology and Biotechnology
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• 제32권4호
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• pp.522-530
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• 2022

In this study we aimed to develop novel ZnO-NP/chitosan/β-glycerophosphate (ZnO-NP/CS/β-GP) antibacterial hydrogels for biomedical applications. According to the mass fraction ratio of ZnO-NPs to chitosan, mixtures of 1, 3, and 5% ZnO-NPs/CS/β-GP were prepared. Using the test-tube inversion method, scanning electron microscopy and Fourier-transform infrared spectroscopy, the influence of ZnO-NPs on gelation time, chemical composition, and cross-sectional microstructures were evaluated. Adding ZnO-NPs significantly improved the hydrogel's antibacterial activity as determined by bacteriostatic zone and colony counting. The hydrogel's bacteriostatic mechanism was investigated using live/dead fluorescent staining and scanning electron microscopy. In addition, crystal violet staining and MTT assay demonstrated that ZnO-NPs/CS/β-GP exhibited good antibacterial activity in inhibiting the formation of biofilms and eradicating existing biofilms. CCK-8 and live/dead cell staining methods revealed that the cell viability of gingival fibroblasts (L929) cocultured with hydrogel in each group was above 90% after 24, 48, and 72 h. These results suggest that ZnO-NPs improve the temperature sensitivity and bacteriostatic performance of chitosan/β-glycerophosphate (CS/β-GP), which could be injected into the periodontal pocket in solution form and quickly transformed into hydrogel adhesion on the gingiva, allowing for a straightforward and convenient procedure. In conclusion, ZnO-NP/CS/β-GP thermosensitive hydrogels could be expected to be utilized as adjuvant drugs for clinical prevention and treatment of peri-implant inflammation.