Evaluation of microneedles-assisted in situ depot forming poloxamer gels for sustained transdermal drug delivery
Evaluation of microneedles-assisted in situ depot forming poloxamer gels for sustained transdermal drug delivery
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DOI：
10.1007/s13346-019-00617-2
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发表时间：
2019-08-01
影响因子：
5.4
通讯作者：
Thakur, Raghu Raj Singh
中科院分区：
文献类型：
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作者：
Khan, Samiullah;Minhas, Muhammad Usman;Thakur, Raghu Raj Singh
在这项研究中，第一次，我们已经报道了一个持续的经皮给药的温度响应泊洛沙姆仓库内形成的皮肤微孔微针（MN）应用程序。首先，我们研究了泊洛沙姆（PF（R）127，P108和P87）在生理条件下的溶胶-凝胶相变特性。评价流变学测量以确认作为模型药物的具有或不具有荧光素钠（FS）的泊洛沙姆制剂在各种浓度下的临界胶凝温度（CGT）。使用小瓶方法对优化的泊洛沙姆制剂进行体外释放研究。其次，使用激光工程硅酮微模具从Gantrez S-97、PEG 10000、PEG 200、PVP K32和PVP K90的各种生物相容性聚合物共混物制造聚合物MN。MN阵列的机械强度，插入力测定，原位溶解动力学，水分含量和渗透深度进行了表征。优化的MN阵列具有良好的机械强度和不溶性的性质，用于在新生猪皮中创建微孔。通过染料结合研究、皮肤完整性评估和组织学研究证实了新生猪皮肤中的微孔。最后，使用垂直Franz扩散池，在非穿孔与微孔皮肤样品中进行FS从优化泊洛沙姆制剂的体外递送。结果得出结论，与维持FS递送72小时的非微孔皮肤相比，FS在含有原位形成贮库泊洛沙姆制剂的MN处理的皮肤样品中的渗透持续96小时。共聚焦显微镜图像证实了在MN处理的皮肤样品与完整皮肤样品的情况下，渗透研究后FS在皮肤组织中的较高荧光强度的分布。
In this study, for the first time, we have reported a sustained transdermal drug delivery from thermoresponsive poloxamer depots formed within the skin micropores following microneedle (MN) application. Firstly, we have investigated the sol-gel phase transition characteristics of poloxamers (PF (R) 127, P108, and P87) at physiological conditions. Rheological measurements were evaluated to confirm the critical gelation temperature (CGT) of the poloxamer formulations with or without fluorescein sodium (FS), as a model drug, at various concentrations. Optimized poloxamer formulations were subjected to in vitro release studies using a vial method. Secondly, polymeric MNs were fabricated using laser-engineered silicone micromolds from various biocompatible polymeric blends of Gantrez S-97, PEG 10000, PEG200, PVP K32, and PVP K90. The MN arrays were characterized for mechanical strength, insertion force determination, in situ dissolution kinetics, moisture content, and penetration depth. The optimized MN arrays with good mechanical strength and non-soluble nature were used to create micropores in the neonatal porcine skin. Microporation in neonatal porcine skin was confirmed by dye-binding study, skin integrity assessment, and histology study. Finally, the in vitro delivery of FS from optimized poloxamer formulations was conducted across non-porated vs microporated skin samples using vertical Franz diffusion cells. Results concluded that permeation of FS was sustained for 96h across the MN-treated skin samples containing in situ forming depot poloxamer formulations compared to non-microporated skin which sustained the FS delivery for 72h. Confocal microscopic images confirmed the distribution of higher florescence intensity of FS in skin tissues after permeation study in case of MN-treated skin samples vs intact skin samples.