DERMAL MICRODIALYSIS SAMPLING IN-VIVO

DERMAL MICRODIALYSIS SAMPLING IN-VIVO
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DOI:
10.1023/a:1018922123774
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发表时间:
1994-11-01
影响因子:
3.7
通讯作者:
LUNTE, CE
LUNTE, CE
中科院分区:
医学3区
文献类型:
--
作者:
AULT, JM;RILEY, CM;LUNTE, CE

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使用线性微透析探针完成真皮在体内的微透析取样。与以前的研究相比,使用商业套管式微透析探针,线性探针通过皮肤在体外的药物通量没有影响。通过组织学检查和微透析递送研究评估探针植入引起的体内组织损伤程度。由于植入线性探头造成的组织损伤极小,未观察到出血或水肿。在探针植入后6小时开始观察到淋巴细胞浸润到组织中,约32小时后开始形成瘢痕组织。淋巴细胞的浸润对微透析探针的植入行为没有影响。对于植入6只不同动物的6种不同探针,5-氟尿嘧啶的递送在20%至25%之间,证明了良好的探针间和植入间重现性。在所有情况下,恒定递送维持至少24小时,表明至少24小时持续时间的实验是可行的。通过植入的微透析探针连续监测局部施用的5-FU乳膏Efudex(R)的皮肤浓度,证明了该技术用于监测体内皮肤药物水平的可行性。局部应用后,5-FU在体外切除皮肤中的真皮浓度约为体内完整皮肤的40倍。
Microdialysis sampling of the dermis in vivo was accomplished using a linear microdialysis probe. In contrast to previous studies using a commercial cannula-style microdialysis probe, the linear probe had no effect on the flux of drug through the skin in vitro. The extent of tissue damage in vivo due to probe implantation was evaluated by histological examination and microdialysis delivery studies. Tissue damage due to implantation of the linear probe was minimal with no bleeding or edema observed. Infiltration of lymphocytes into the tissue was observed beginning 6 hours after probe implantation with scar tissue beginning to form after approximately 32 hours. The infiltration of lymphocytes had no effect on the behavior of implanted microdialysis probes. Delivery of 5-fluorouracil was between 20 and 25% for six different probes implanted in six different animals demonstrating good probe-to-probe and implantation-to-implantation reproducibility. Constant delivery was maintained for at least 24 hours in all cases indicating that experiments of at least 24 hour duration are feasible. The dermal concentration of topically applied 5-FU cream, Efudex(R), was continuously monitored by an implanted microdialysis probe demonstrating the feasibility of this technique as for monitoring skin drug levels in vivo. The dermal concentration of 5-FU following topical application was approximately 40-fold higher for in vitro excised skin than for in vivo intact skin.