Poloxamer hydrogel의 물성 및 약물조절 방출에 관한 연구

Abstract

Ethylene oxide와 propylene oxide의 block copolymer인 poloxamer가 triisocyanate로 가교되고 diisocyanate로 extended된 hydrogel을 제조하였다. 친수성/소수성 모델약물을 선정하여 crosslinker와 extender의 비율 조절에 따른 hydrogel의 약물방출 조절능을 조사하였으며 팽윤실험을 실시하여 그 기전을 규명하고자 하였다. 가교부위에 urethane bond를 함유한 poloxamer gel은 건조상태에서도 rubber elasticity를 보였으며 extender의 비율이 증가할수록 이 rubber elasticity는 더 커졌다. 또한 가교도가 감소할수록 팽윤도가 상승하였고 이에따른 약물방출도 증가함을 확인하였다. 제조된 hydrogel에 조절방출시 필요한 특수 기능성을 부가시키고자 기능성 고분자인 poly(acrylic acid)와 IPN공중합체를 합성하여 pH에 의한 equilibrium팽윤도를 조사하였고 비이온성/양이온성/음이온성 모델약물을 선택하여 pH에 따른 가변적 팽윤도와 이온성 상호작용등에 근거한 약물 방출 실험을 함으로써 조절방출기전을 규명하고자 하였다. IPNs은 poly(acrylic acid), poloxamer의 homopolymer hydrogel과 비교시 equilibrium팽윤도에 큰 변화가 있었으며 pH 2와 pH 7에서의 가변적 팽윤에 의하여 약물의 방출속도 또한 조절 가능 했다. 양 이온성 약물의 경우 pH 2와 PH 7에서의 높은 팽윤도의 차이에도 불구하고 음이온성 약물과 비교시 pH 7에서의 초기 방출량이 상당히 감소하여 pH 2에서와 비슷한 방출양상을 나타냈는데 이는 IPNs의 carboxylic group과 약물의 이온성, 그리고 IPNs내의 interpolymer interaction이 복합적으로 작용한 결과로 사료된다.;Poloxamer, block copolymers of ethylene oxide and propylene oxide was crosslinked by diisocyanates and triisocyanates to form water-swellable, physically strong, rubber-like elastic, high biocompatible polyurethanes. The isocyanate-hydroxyl stoichiometry was kept 1:1, but the crosslinking density was varied. The variations examined were the ratio of diisocynate and triisocyanate The delivery of two drugs of different water solubilities from hydrogel matrices was studied. It appeared that the drug nature greatly influenced its release kinetics possibly due to drug-polymer interactions. The release profiles, however, could be modified to a great extent by adjusting the polymer network structure. Generally, the high crosslinking density was required for prolonged drug delivery. Poloxamer-poly(acrylic acid)(PAA) interpenetrating polymer networks (IPNs) were prepared via matrix polymerization of acrylic acid(AA) with poloxamer prepolymer. The equilibrium swelling of poloxamer/PAA IPNs was determined in various pH medium. The swelling of poloxamer/PAA IPNs was more affected by pH differences compared with the swelling of homo PAA gel due to protonation and deprotonation of the PAA network, followed by reversible formation and dissociation of the interpolymer complex due to hydrogen bonding between acidic hydrogens and ether oxygens. Nonionic/anionic/cationic drugs were incorporated into IPN matrices as a model drug and their release behavior was studied. Nonionic drug revealed release patterns depending solely on p H dependent swelling kinetics. In contrast, The release of ionic drugs was significantly affected by ionic drug-polymer interaction as well as the swelling kinetics.