A polymeric device for delivery of anti-microbial and anti-fungal drugs in the oral environment: effect of temperature and medium on the rate of drug release
A polymeric device for delivery of anti-microbial and anti-fungal drugs in the oral environment: effect of temperature and medium on the rate of drug release
复制标题
DOI：
10.1016/s0109-5641(02)00109-4
复制
发表时间：
2003-11-01
期刊：
影响因子：
5
通讯作者：
Offenbacher, S
中科院分区：
文献类型：
--
作者：
Lin, DM;Kalachandra, S;Offenbacher, S
目标。药物输送系统在牙科中的应用是一个相对较新的研究领域，但聚烯酸类粘固剂及其前身硅酸盐粘固剂的氟离子释放除外。本研究基于一种生物相容材料乙烯-乙酸乙烯酯共聚物(EVA)的使用，该材料能够在较长时间内以适合口腔疾病治疗的剂量持续释放治疗水平的药物。将EVA和药物按40：1的比例加入70ml二氯甲烷中38℃下溶解6h，制成聚合物浇注液，用溶剂挥发技术从干燥的薄片上切割出厚度为1 mm的3×3 cm(2)的薄层。载药样品在10ml(双蒸水或水/乙醇(4：1))中提取至少14天，每天更换。光谱测量跟踪释放动力学过程中光密度(OD)的变化。研究了温度(24℃和37℃)对药物释放速率的影响，并用Arrehenius方程计算了盐酸四环素(TTH)、盐酸多西环素(DOH)和二乙酸氯己定(CDA)分子在水中扩散(移位)的活化能。考察了提取介质(水和水/乙醇(4：1))对24℃释药速率的影响。数据的方差分析表明，在更高的温度(37℃)下，当提取介质改为水/乙醇(4：1)时，TTH、DOH和CDA的提取速率显著提高(p<；0.0015)。增强的速率值似乎是由于聚合物中通道的形成。CDA的最大活化能(21.83千卡摩尔~(-1))是由于其平均相对分子质量(626)高于TTH(481)和DOH(481)，具有重要意义。这些体外药物释放速率的测量将为建立一种新的方法(治疗方式)提供基础，以使用牙医容易获得的实验室方法和材料在较长的时间内持续口腔内给药。(C)2003年牙科材料学会。爱思唯尔科学有限公司出版。版权所有。
Objectives. The use of drug delivery systems in dentistry is a relatively new area of research with the exception of fluoride ion release from polyalkenoate cements and their predecessor silicate cements. The present study is based on the use of a bio-compatible material ethylene vinyl acetate copolymer (EVA) that enables constant release of drugs of therapeutic levels over extended periods of time at doses suitable for the treatment of oral conditions.Method. Polymer casting solutions were made by dissolving EVA and the drug in the ratio of 40:1 in 70 ml of dichloromethane at 38 degreesC for 6 h. Thin square films of 3 X 3 cm(2) with a thickness of 1 mm were cut from the dry sheet obtained by solvent evaporation technique. Drug loaded samples were extracted for a minimum of 14 days in 10 ml medium (double distilled water or water/ethanol (4: 1)) which was replaced daily. Spectral measurements were made to follow changes in optical densities (OD) during release kinetics. Effect of temperature (24 and 37 degreesC) on the rate of drug release was studied and the energies of activation (DeltaE(not equal)) were calculated using Arrehenius equation for the diffusion (translocation) of molecules of tetracycline hydrochloride (TTH), doxycycline hydrochloride (DOH), and chlorhexidine diacetate (CDA) in water as extracting medium. Effect of extracting medium (water and water/ethanol (4:1)) was also investigated on the rate of drug release measurements at 24 degreesC.Results. Analysis of variance of the data revealed that significantly enhanced rates were observed at the higher temperature (37 degreesC) and when extracting medium was changed to water/ethanol (4: 1) for TTH, DOH and CDA (p < 0.0015). The enhanced rate values seem to be due to the formation of channels in the polymer. The largest activation energy (21.83 kcal mol(-1)) observed for CDA was interpreted as due to the highest average molecular weight (626) compared to TTH (481) and DOH (481).Significance. These in vitro rate of drug release measurements will provide a basis for establishing a novel approach (treatment modality) for sustained intra-oral drug delivery over extended time periods using laboratory methods and materials that are readily available to dentists. (C) 2003 Academy of Dental Materials. Published by Elsevier Science Ltd. All rights reserved.