Formulation and in-vitro and in-vivo evaluation of a mucoadhesive gel containing freeze dried black raspberries:: Implications for oral cancer chemoprevention
Formulation and in-vitro and in-vivo evaluation of a mucoadhesive gel containing freeze dried black raspberries:: Implications for oral cancer chemoprevention
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DOI：
10.1007/s11095-006-9192-1
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发表时间：
2007-04-01
影响因子：
3.7
通讯作者：
Mumper, Russell J.
中科院分区：
文献类型：
--
作者：
Mallery, Susan R.;Stoner, Gary D.;Mumper, Russell J.
本研究的目的是制备含有冻干黑树莓(FBR)的粘附凝胶，并确定FBR生物活性化合物的最佳参数，包括花青素的稳定性、吸收和体内外渗透。浆果凝胶的FBR分别为5%和10%(w/w)，最终的PHS为3.5~7.5。建立了测定凝胶中花色苷稳定性的高效液相色谱分析方法。当凝胶被应用于口腔粘膜时，进行了单一时间点的研究以确定花青素的吸收。花色苷在人体口腔组织外植体中的渗透率与凝胶pH和FBR含量有关。用高效液相色谱-质谱法测定了口腔组织外植体、唾液和血液中的花色苷含量，凝胶中花色苷的稳定性与凝胶的pH值和储存温度直接相关。在较低的pH值(pH 3.5)和较低的贮藏温度(4℃)下，花色苷的稳定性最好。粘附性浆果凝胶制剂中所含的花青素很容易被人体口腔粘膜组织吸收，这一点在凝胶使用后5分钟内就能检测到。浆果凝胶的最终pH值为6.5，而浆果凝胶的最终pH值为3.5，花色苷在组织外植体中的渗透率有提高的趋势。描述了一种用于将化学预防化合物局部输送到人类口腔粘膜组织的新型凝胶配方和特性。结果表明，花色苷的稳定性依赖于凝胶的pH值和储存温度，也表明凝胶成分非常适合于吸收和渗透到目标口腔粘膜组织部位。
The purpose of these studies was to formulate mucoadhesive gels containing freeze dried black raspberries (FBR) and to determine optimum parameters for a subset of FBR bioactive compounds including anthocyanin stability, absorption and penetration in-vitro and in-vivo.Berry gels were prepared having FBR at 5% and 10% w/w and final pHs ranging from 3.5 to 7.5. A HPLC assay was developed to quantify and determine the stability of the anthocyanins in the gels. A single time-point study was performed to determine anthocyanin uptake when the gels were applied to oral mucosa. Penetration of anthocyanins into human oral tissue explants was determined as a function of gel pH and FBR content. A HPLC-mass spectroscopy assay was utilized to quantify the anthocyanin levels in human oral tissue explants, saliva, and blood.The stability of anthocyanins in the gel was directly related to gel pH and storage temperature. Maximum stability of anthocyanins was found at lower pH (pH 3.5) and storage temperature (4 degrees C). Anthocyanins contained in mucoadhesive berry gel formulations were readily absorbed into human oral mucosa tissue as evidenced by detectable blood levels within 5 min after gel application. There was a trend for greater penetration of anthocyanins into tissue explants for berry gels with a final pH of 6.5 versus pH 3.5.Formulation and characterization of a novel gel formulation for local delivery of chemopreventive compounds to human oral mucosal tissues has been described. The results show anthocyanin stability was dependent upon gel pH and storage temperature and also demonstrate that the gel composition is well-suited for absorption and penetration into the target oral mucosal tissue site.