• 생체재료학회지
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• 제22권4호
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• pp.249-258
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• 2018

Background: Mucoadhesive polymers, which may increase the contact time between the polymer and the tissue, have been widely investigated for pharmaceutical formulations. In this study, we developed a new polysaccharide-based mucoadhesive polymer with thermogelling properties. Methods: Hexanoyl glycol chitosan (HGC), a new thermogelling polymer, was synthesized by the chemical modification of glycol chitosan using hexanoic anhydride. The HGC was further modified to include thiol groups to improve the mucoadhesive property of thermogelling HGC. The degree of thiolation of the thiolated HGCs (SH-HGCs) was controlled in the range of 5-10% by adjusting the feed molar ratio. The structure of the chemically modified polymers was characterized by $^1H$ NMR and ATR-FTIR. The sol-gel transition, mucoadhesiveness, and biocompatibility of the polymers were determined by a tube inverting method, rheological measurements, and in vitro cytotoxicity tests, respectively. Results: The aqueous solution (4 wt%) of HGC with approximately 33% substitution showed a sol-gel transition temperature of approximately $41^{\circ}C$. SH-HGCs demonstrated lower sol-gel transition temperatures ($34{\pm}1$ and $31{\pm}1^{\circ}C$) compared to that of HGC due to the introduction of thiol groups. Rheological studies of aqueous mixture solutions of SH-HGCs and mucin showed that SH-HGCs had stronger mucoadhesiveness than HGC due to the interaction between the thiol groups of SH-HGCs and mucin. Additionally, we confirmed that the thermogelling properties might improve the mucoadhesive force of polymers. Several in vitro cytotoxicity tests showed that SH-HGCs showed little toxicity at concentrations of 0.1-1.0 wt%, indicating good biocompatibility of the polymers. Conclusions: The resultant thiolated hexanoyl glycol chitosans may play a crucial role in mucoadhesive applications in biomedical areas.

• 폴리머
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• 제37권5호
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• pp.625-631
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• 2013

점막접착 기능은 인체의 다양한 장기에 적용되는 의료용 접착제에 요구되는 중요한 특성이며, 점막접착 기능을 갖는 고분자를 개발하기 위하여 많은 연구가 이루어지고 있다. 최근 많은 연구자들이 생체모방 기술을 통한 점막접착형 고분자를 개발하고 있고, 그 중 해양 부착 생물인 홍합의 접착 기능 및 특성이 접착제 연구의 주요 대상이 되어왔다. 본 연구에서는 홍합 접착 물질 속에 과량 존재해 표면 접착 기능을 발현하는 카테콜 구조가 도입된 생체모방형 고분자를 합성하였고, 핵자기공명분광법 및 젤투과크로마토그래피를 사용하여 분석하였다. In vitro 상에서 돼지의 소장점막하조직 sheet를 준비하여 전단 시편을 제작하고 점막접착력을 측정하였다. 점막접착형 고분자는 현재 상업적으로 사용되고 있는 대조군인 피브린글루와 비교할 때 월등한 접착력을 보였다. 또한, 다양한 인자를 변화시키며 최적의 점막접착력을 나타내는 조건을 확립하였다. 이러한 결과들을 토대로 우수한 점막접착형 특성을 나타내는 고분자를 개발하였고 다양한 임상적용 및 의료용 기기에 도입가능한 소재의 기초연구를 수행하였다고 사료된다.

• 폴리머
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• 제36권2호
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• pp.182-189
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• 2012

본 연구에서는 전자빔을 이용하여 폴록사머 하이드로젤을 제조하여 구강 점막부착성 약물전달체로서의 특성을 평가하고자 하였다. 온도감응성을 나타내는 폴록사머 고분자의 말단에 가교반응을 위한 비닐기를 도입한 후, 방사선 가교반응을 이용하여 하이드로젤을 제조하였다. 점착성 향상을 위한 첨가제로 점착성 고분자인 카보폴을 첨가하여 하이드로젤을 제조하였고, 카보폴이 점막부착성과 서방성 방출에 미치는 영향을 알아보았다. 결과적으로, 폴록사머 고분자의 말단 개질과 카보폴의 첨가에 의해 하이드로젤의 기계적 물성과 점막부착성이 향상되었고, 약물방출실험 결과 약물이 방출되는 속도가 지연되는 결과를 확인하였다.

• Advances in Traditional Medicine
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• 제7권1호
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• pp.51-64
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• 2007

Mucus is an aqueous gel complex with a constitution of about 95% water, high molecular weight glycoprotein (mucin), lipid, salts etc. Mucus appears to represent a significant barrier to the absorption of some compounds. Natural mucoadhesive agent was isolated and purified from the aqueous extract of the seeds of prosopis pallida (PP). Formulated tablet with the isolated material by wet granulation method. Some natural edible substances are in consideration for candidates as mucoadhesive agents to claim more effective controlled drug delivery as an alternative to the currently used synthetic mucoadhesive polymers. Subjected the materials obtained from natural source i.e. PP and standard synthetic substance, sodium carboxymethyl cellulose for evaluation of mucoadhesive property by various in vitro and in vivo methods. Through standard dissolution test and a model developed with rabbit, evaluated in vitro controlled release and bioadhesive property of theophylline formulation. Mucoadhesive agent obtained from PP showed good mucoadhesive potential in the demonstrated in vitro and in viνo models. The results suggest that the mucoadhesive agent showed controlled release properties by their application, substantially. In order to assess the gastrointestinal transit time in vivo, a radio opaque X-ray study performed in healthy rabbit testing the same controlled release formulation with and without bioadhesive polymer. Plasma levels of theophylline determined by the HPLC method and those allowed correlations to the in vitro mucoadhesive study results. Better correlation found between the results in different models. PP may acts as a better natural mucoadhesive agent in the extended drug delivery system.

• Journal of Pharmaceutical Investigation
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• 제25권4호
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• pp.339-345
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• 1995

For the effective treatment of aphthous stomatitis, the matrix type mucoadhesive patches containing triamcinolone acetonide have been formulated. The drug layer was obtained by drying the polymer gel which was prepared with carbomer 934P, ammoniomethacrylate copolymer, titanium dioxide and polyethylene glycol 400. The effects of the content of additives on physical characteristics of the polymer gel and the drug layer were evaluated. The addition of carbomer increased the yield point and the zero-shear viscosity of polymer gel as well as the thickness, the water absorption ratio, the adhesive time and $T_{50%}$ of drug layer. The adhesive time and the water absorption ratio of drug layer were also improved by the addition of ammoniomethacrylate copolymer, but the addition of titanium dioxide had decreased the zero-shear viscosity of polymer gel and the adhesive time of drug layer.

• Journal of Pharmaceutical Investigation
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• 제36권2호
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• pp.83-87
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• 2006

Poly(acrylic acid) (PAA) was identified to possess good mucoadhesive properties ensuring its application to extend the retention times of the formulations at the oral cavity, intended route of administration using the polymer. In the noncross-linked state, PAA will swell and become eroded owing to the presence of salivary flow from the site of application. The formation of cross-links between the polymer chains will allow swelling but prevents the erosion of the dosage form. In the current study, cross-linking was achieved by esterification of the PAA chains with sucrose. The density of crosslinking was modified by changing sucrose concentration and the duration of cure time. The cross-linking density of the polymer hydrogel was assessed by equilibrium swelling studies. The mucoadhesion testing method allowed a comparative study of the hydrogels prepared. An inverse relationship between equilibrium swelling and peak detachment force showed that increased PAA chain density per unit area enhanced the mucoadhesive interaction.

• Biotechnology and Bioprocess Engineering:BBE
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• 제10권6호
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• pp.516-521
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• 2005

Drug delivery to the lymphatic system may be important in terms of the treatment with lymphatic involvement, such as tumor metastases and immunization. Especially, drug transport via the intestinal lymphatics after oral administration has been attracted lots of interests. The purpose of this study was to prepare cyclosporin A (CSA)-loaded liposomes, with different characteristics, and evaluate their mucoadhesivity. Three liposome preparations were formulated: cationic stearylamine liposomes (SA-Lip), anionic phosphatidylserine liposomes (PS-Lip), Polymer (chitosan)-coated liposomes (CS-Lip), and characterized. The liposome preparations were found to be spherical in shape, with PS-Lip being the smallest. The liposome preparations exhibited entrapment efficiencies in the order: PS-Lip $(52.5{\pm}2.9%)$ > SA-Lip $(48.8{\pm}3.3%)$ > CS-Lip $(41.7{\pm}4.2%)$. Finally, mucoadhesive tests were carried out using rat intestine, with SA-Lip (67%) showing the best adhesive rate of the three preparations (PS-Lip: 56%, CS-Lip: 61%). These results suggest that a positive charge on the surface of drug carriers may be an important factor for the intestinal drug delivery.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2002년도 창립10주년기념 및 국립독성연구원 의약품동등성평가부서 신설기념 국재학술대회:생물학적 동등성과 의약품 개발 전략을 위한 국제심포지움
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• pp.212-212
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• 2002

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.235.2-235
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• 2003

To develop the buccal delivery system of rhEGF for the treatment of buccal mucosal ulcer, polymer films and hydrogels were investigated. Methods: Hydrogels for thermosenstive sol/gel systems were prepared by the cold method (Schmolka, 1972). And mucoadhesive films were prepared by mixing sod. alginate/polycarbophil 974p. To find an optimum buccal mucosal adhesive gel or film, the gel strength of the poloxamer and sod. alginate/polycarbophil 974p hydrogels were determined by the Simple Rheology Method and their mucoadhesiveness were measured by the Instron (M 4400, Instron Co., U.S.A.) method. (omitted)

• Journal of Pharmaceutical Investigation
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• 제36권6호
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• pp.393-399
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• 2006

This study was aimed to design, formulate and characterize the moisture-activated patches containing acyclovir for antiviral action. Gel intermediates for film-type patches were prepared with mucoadhesive polymer, viscosity builders, enhancers and acyclovir. Patches containing acyclovir were characterized by in vitro measurement of drug release rates through a cellulose barrier membrane, and of drug flux through the hairless mouse skin. Film-type patches obtained were uniform in the thickness and showed a mucoadhesive property when contacted with moisture. The formulation was optimized, which consisted of $Cantrez^{\circledR}$ AN-169(2%), $Kollidon^{\circledR}$ VA 64(1%), $Natrosol^{\circledR}$(1%), hydroxypropyl-$\beta$-cyclodextrin(1%) and dimethylsulfoxide(0.5%). Release rates of acyclovir patches increased dose-dependently. The addition of terpenes such as d-limonene or cineole increased release rates of acyclovir, but decreased permeation rates. The permeation rates were enhanced by 2 and 2.5 times by the addition of glycyrrhizic acid ammonium salt and sodium glycocholate, respectively, compared with that of no enhancer. These results suggest that it may be feasible to deliver acyclovir through the skin or gingival mucosa from the moisture-activated patches.