包覆涂层的可溶性微针的制备及性能测试

Fabrication and evaluation of coated-dissolving microneedles

近年来,可溶性微针因其优势引起了科学家的广泛关注,但由于可溶性高分子材料快速溶解的特性,较难实现药物的缓控释.笔者提出了一种在可溶性微针针体上包覆一层涂层的方法,以实现对药物释放行为的控制.采用自制的旋涂机在微针针体上包覆一层缓释涂层,以透皮扩散试验探究高分子涂层材料的种类和浓度、旋涂机的转速、包覆的次数等参数对药物释放的影响规律;采用力学强度测试和皮肤穿刺试验考察微针的穿刺行为和效率,最后通过经皮水分流失测试和皮肤恢复情况来评估微针的安全性.通过上述方法,成功制备了可实现缓控释的微针,优选的高分子涂层材料为聚苯乙烯,优选浓度为3%,旋涂机转速为600 r·min^(-1),包覆次数1次为宜;4种不同的药物均可用上述包覆的方法实现药物的缓控释.研究结果表明,包覆涂层的微针每根能承受至少0.21 N·tip^(-1),能够有效地刺入皮肤,穿刺皮肤效率达到97.20%.经皮水分流失测试结果显示,微针刚处理后经皮水分流失值升高至(54.03±3.85)g·m^(-2)·h^(-1),6 h后便下降到正常水平((13.80±1.37)g·m^(-2)·h^(-1))(与对照组无显著性差异),表明皮肤已恢复屏障作用.笔者所制备的微针可以实现多种药物的缓控释,具有足够的机械强度,而且相对安全,是一种具有较大潜力的新型药物载体.

Dissolving microneedles have been paid much attention to recently because of their special advantages.However,due to the rapid dissolution of soluble polymer materials,it is difficult to achieve sustained and controlled release of drugs.Herein,a coating method was proposed to control the drug release behavior of microneedles.A self-made spin coating machine was set up and used to coat a layer of slow-release coating on the tip of the microneedles,and the effects of the type and concentration of polymer materials,the rotation speed of the coating machine and the times of coating on drug release behavior were investigated by transdermal diffusion test.The penetration behavior and efficiency of the microneedles were investigated by mechanical strength test and skin puncture test.Finally,the transepidermal water loss test and skin recovery observation were carried out to evaluate the safety of the microneedles.The microneedles with sustained and controlled release profile were successfully prepared by using the following parameters,including 3%polystyrene solution,the rotating speed of the coating machine(600 r·min^(-1))and the coating times(1 time).The coating method mentioned above has been used to achieve the sustained and controlled release of four drugs.Each coated microneedles could endure at least 0.21 N·tip^(-1) and effectively penetrate into the skin,and the skin penetration efficiency reached 97.20%.The results of transepidermal water loss test showed that the value of transepidermal water loss increased to(54.03±3.85)g·m^(-2)·h^(-1) immediately after the treatment of microneedles,and then decreased to the normal level of(13.80±1.37)g·m^(-2)·h^(-1) after 6 hours(there was no significant difference between the two groups),indicating that the skin had recovered its barrier function.The microneedles proposed in this study could realize the sustained and controlled release of many drugs with sufficient mechanical strength and relatively safety,suggesting it is a new drug carrier with great potential.