Han Sang Mi, Kim Se Gun, Pak Sok Cheon
Rural Development Administration, National Academy of Agricultural Science, Wanju, Chonbuk 55365, Korea.
School of Biomedical Sciences, Charles Sturt University, Bathurst, NSW 2795, Australia.
Molecules. 2017 May 19;22(5):836. doi: 10.3390/molecules22050836.
Bee venom (BV) has long been used as a traditional medicine. The aim of the present study was to formulate a BV emulsion with good rheological properties for dermal application and investigate the effect of formulation on the permeation of melittin through dermatomed rat skin. A formulated emulsion containing 1% (/) BV was prepared. The emulsion was compared with distilled water (DW) and 25% (/) -methyl-2-pyrrolidone (NMP) in DW. Permeation of melittin from aqueous solution through the dermatomed murine skin was evaluated using the Franz diffusion cells. Samples of receptor cells withdrawn at pre-determined time intervals were measured for melittin amount. After the permeation study, the same skin was used for melittin extraction. In addition, a known amount of melittin (5 μg/mL) was added to stratum corneum, epidermis, and dermis of the rat skin, and the amount of melittin was measured at pre-determined time points. The measurement of melittin from all samples was done with HPLC-MS/MS. No melittin was detected in the receptor phase at all time points in emulsion, DW, or NMP groups. When the amount of melittin was further analyzed in stratum corneum, epidermis, and dermis from the permeation study, melittin was still not detected. In an additional experiment, the amount of melittin added to all skin matrices was corrected against the amount of melittin recovered. While the total amount of melittin was retained in the stratum corneum, less than 10% of melittin remained in epidermis and dermis within 15 and 30 min, respectively. Skin microporation with BV emulsion facilitates the penetration of melittin across the stratum corneum into epidermis and dermis, where emulsified melittin could have been metabolized by locally-occurring enzymes.
蜂毒（BV）长期以来一直被用作传统药物。本研究的目的是制备一种具有良好流变学性质的用于皮肤给药的BV乳液，并研究该制剂对蜂毒肽透过离体大鼠皮肤渗透的影响。制备了一种含1%（/）BV的制剂乳液。将该乳液与蒸馏水（DW）以及DW中25%（/）的N - 甲基 - 2 - 吡咯烷酮（NMP）进行比较。使用Franz扩散池评估蜂毒肽从水溶液透过离体小鼠皮肤的渗透情况。在预定的时间间隔取出受体池中的样品，测量蜂毒肽含量。渗透研究结束后，使用相同的皮肤进行蜂毒肽提取。此外，向大鼠皮肤的角质层、表皮和真皮中添加已知量的蜂毒肽（5μg/mL），并在预定时间点测量蜂毒肽含量。所有样品的蜂毒肽测量均采用高效液相色谱 - 串联质谱法（HPLC - MS/MS）。在乳液、DW或NMP组的所有时间点，受体相中均未检测到蜂毒肽。当对渗透研究中角质层、表皮和真皮中的蜂毒肽含量进行进一步分析时，仍未检测到蜂毒肽。在另一项实验中，针对回收的蜂毒肽量对添加到所有皮肤基质中的蜂毒肽量进行校正。虽然蜂毒肽总量保留在角质层中，但在15分钟和30分钟内，分别只有不到10%的蜂毒肽保留在表皮和真皮中。用BV乳液进行皮肤微孔穿刺可促进蜂毒肽穿过角质层进入表皮和真皮，在那里乳化的蜂毒肽可能已被局部存在的酶代谢。
