CN113577042A - 一种用于皮肤疾病靶向诊疗的可溶性微针贴片及其制备 - Google Patents
一种用于皮肤疾病靶向诊疗的可溶性微针贴片及其制备 Download PDFInfo
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- CN113577042A CN113577042A CN202110807702.0A CN202110807702A CN113577042A CN 113577042 A CN113577042 A CN 113577042A CN 202110807702 A CN202110807702 A CN 202110807702A CN 113577042 A CN113577042 A CN 113577042A
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Abstract
本发明涉及一种用于皮肤疾病靶向诊疗的可溶性微针贴片及其制备,属于生物医药技术领域。包括基座和聚合物针体,聚合物针体以阵列形式位于基座上,形成聚合物针体的聚合物能溶于水,聚合物针体的针尖部分分散有纳米药物颗粒。制备方法为:将微针阵列阴模用氧等离子体处理,使微针阵列阴模表面亲水;将纳米药物溶液滴在微针阵列阴模表面进行离心处理,将能溶于水的聚合物溶液注入微针阵列阴模,进行抽真空、干燥,将微针与阴模剥离,即得到微针贴片。本发明合成的微针贴片可实现药物颗粒在皮肤疾病治疗中代谢行为的实时监测,解决了纳米药物的经皮给药在皮肤疾病治疗中,透皮效果差、药物代谢行为不可控以及疗效不理想等技术问题。
Description
技术领域
本发明属于生物医药技术领域,更具体地,涉及一种用于皮肤疾病靶向诊疗的可溶性微针贴片及其制备。
背景技术
皮肤是人体最大的器官,覆盖于体表,其作用主要是为机体提供屏障保护,是人体内环境和外环境的分界,对于维持人体内环境的稳态有重要的意义。如今影像学技术为疾病的诊疗提供有力的工具,但是如何实现皮肤相关疾病的诊疗一体化目前研究尚少,靶向纳米颗粒药物载体的开发往往需要复杂的合成方案,包括超分子自组装和化学修饰,这些过程通常很难预测、执行和控制。一些治疗性药物与特定的小分子近红外染料如IR783能够在一定条件下发生自组装,形成具有超高载药量的稳定纳米粒子。将近红外荧光染料与皮肤疾病治疗进行有效地结合,可以指导医生进行临床诊断和治疗,改善患者的生活质量,为皮肤疾病精准个体化治疗提供了新的途径。这种基于小分子近红外染料的纳米颗粒系统,是纳米医学的一个重要补充,使高载药的纳米载体快速产生,用于皮肤疾病的高效诊断和治疗。
近年来微针技术在生物医学领域得到了广泛的应用,微针给药不仅可以提高给药精度和药物利用效率,同时还具有传输速度快、无痛和微量的特点。微针在处理皮肤后可以瞬间在皮肤表面形成可逆、能够自行恢复的微孔道,从而使药物活性成分透过角质层障碍直接到达皮肤深层,将药物活性成分准确定位、精确定量的输送到需要改善或治疗的部位,充分发挥药物功效。微针一般分为固体微针、涂层微针、空心微针和可溶性微针,其中,聚合物微针具有极好的生物相容性,可用的材料种类丰富、价格低廉,易于实现规模化生产。
发明内容
本发明合成的纳米颗粒药物粒径可控且自带荧光性质,可实现纳米药物在皮肤疾病治疗中代谢行为的实时监测,解决了纳米药物的经皮给药在皮肤疾病治疗中,透皮效果差、药物代谢行为不可控以及疗效不理想等技术问题,为他人设计相应的纳米药物应用于皮肤疾病的治疗提供数据支持和理论参考,同时解决了一种载有小分子纳米颗粒药物的微针贴片的制备问题。
根据本发明的目的,提供了一种微针贴片,该微针贴片包括基座和聚合物针体,所述聚合物针体以阵列形式位于基座上,形成所述聚合物针体的聚合物能溶于水,所述聚合物针体的针尖部分分散有纳米药物颗粒,所述纳米药物颗粒为药物与荧光分子自组装形成的纳米粒子。
优选地,所述药物为曲美替尼、索拉菲尼、紫杉醇、雷帕霉素、佛维司群和恩杂鲁胺中的至少一种;所述荧光分子为近红外染料IR783。
优选地,形成所述聚合物针体的聚合物为聚甲基丙烯酸甲酯、聚乳酸、聚乳酸与羟基乙酸共聚物、聚乙醇酸、聚碳酸酯、环烯烃共聚物、聚乙烯基吡咯烷酮、聚乙烯醇、聚苯乙烯、聚甲基乙烯基醚与马来酸酐共聚物、透明质酸、壳聚糖、羟丙基纤维素、羟乙基纤维素、海藻酸钠和明胶中的至少一种。
优选地,所述聚合物针体的密度为25-400根/平方厘米基底;所述聚合物针体的高度为100-1500μm;所述微针贴片的聚合物针体阵列的机械强度为40-200MPa。
优选地,所述微针贴片的聚合物针体阵列含有纳米药物颗粒1-500μg。
优选地,所述聚合物针体呈圆锥形或棱锥形。
优选地,圆锥形针体的底边直径为50-1000μm。
按照本发明的另一方面,提供了任一所述的微针贴片的制备方法,包括以下步骤:
(1)将微针阵列阴模用氧等离子体处理,使微针阵列阴模表面亲水;将纳米药物的溶液滴在微针阵列阴模表面进行离心处理,使纳米药物颗粒进入微针阵列阴模的微孔中;所述纳米药物为药物与荧光分子自组装形成的纳米粒子;
(2)将能溶于水的聚合物溶液注入微针阵列阴模,并进行抽真空处理,然后进行干燥,干燥后将微针与阴模剥离,即得到装载有纳米药物颗粒的微针贴片;
优选地,所述药物与荧光分子自组装形成的纳米粒子具体制备方法为:将药物和荧光分子分别溶解,得到药物溶液和荧光分子溶液,将所述药物溶液逐滴加入到荧光分子溶液中,并不断搅拌,离心去除游离药物后得到的固体沉淀即为药物与荧光分子自组装形成的纳米粒子。
优选地,步骤(1)中所述纳米药物溶液的浓度为10-50mg/mL;步骤(2)中所述聚合物溶液的浓度为100-1000mg/mL。
按照本发明的另一方面,提供了任一所述的微针贴片用于制备皮肤疾病靶向诊疗贴片的应用。
总体而言,通过本发明所构思的以上技术方案与现有技术相比,主要具备以下的技术优点:
(1)由于皮肤屏障的存在,传统的涂抹类、贴敷类药物中的有效成分很难透过皮肤角质层,透皮效率均不超过5%,存在着利用率低、疗效不佳的治疗难点。本发明的一种可用于皮肤疾病靶向诊疗的可溶性微针贴片及其制备,首先解决了纳米药物的经皮给药在皮肤疾病治疗中透皮效果差,因而导致疗效不理想的治疗难点;其次可实现对纳米药物在皮肤疾病治疗中代谢行为的实时监测,解决传统方法中药物代谢行为不可控的技术问题;最后,该发明为他人设计相应的纳米药物应用于皮肤疾病的治疗提供数据支持和理论参考,同时解决了一种载有小分子自组装纳米药物的微针贴片的制备问题。
(2)本发明中的可溶性聚合物具有良好的生物相容性,可以得到机械性能极佳,能够透皮效果的微针,可以瞬间在皮肤表面形成可逆、能够自行恢复的微孔道,从而使药物活性成分透过角质层障碍直接到达皮肤深层,将药物活性成分准确定位、精确定量的输送到需要改善或治疗的部位,充分发挥药物功效。
附图说明
图1为本发明一种用于皮肤疾病靶向诊疗的微针贴片示意图,其中:1-自组装纳米颗粒、2-微针针体、3-微针基座。
图2为本发明雷帕霉素@IR783自组装纳米颗粒透射电子显微镜镜图。
图3为本发明雷帕霉素@IR783自组装纳米颗粒粒径分布图。
图4为本发明载有雷帕霉素@IR783自组装纳米颗粒的微针贴片皮肤镜图。
图5为本发明载有雷帕霉素@IR783自组装纳米颗粒的微针贴片透射电子显微镜图。
图6为本发明制备的一种用于皮肤疾病靶向诊疗的微针贴片在小鼠皮肤疾病诊断中的示意图。
具体实施方式
为了使本发明的目的、技术方案及优点更加清楚明白,以下结合附图及实施例,对本发明进行进一步详细说明。应当理解,此处所描述的具体实施例仅仅用以解释本发明,并不用于限定本发明。此外,下面所描述的本发明各个实施方式中所涉及到的技术特征只要彼此之间未构成冲突就可以相互组合。
本发明一种用于皮肤疾病靶向诊疗的微针贴片,图1为本发明一种用于皮肤疾病靶向诊疗的微针贴片示意图,该微针贴片包括微针基座3、位于微针基座3上的微针针体2,载有自组装纳米药物颗粒1位于微针针体2的针尖部分。基座、针体和针尖为一体成型,自组装纳米药物颗粒均匀散布在针尖。
一些实施例中,所述自组装纳米药物颗粒为曲美替尼@IR783自组装纳米颗粒、索拉菲尼@IR783自组装纳米颗粒、紫杉醇@IR783自组装纳米颗粒、雷帕霉素@IR783自组装纳米颗粒、佛维司群@IR783自组装纳米颗粒、恩杂鲁胺@IR783自组装纳米颗粒中的任意一种或多种混合。
一些实施例中,微针针体2为可溶性的聚合物针体,可溶性聚合物具有良好的生物相容性的可降解材料制成,为聚甲基丙烯酸甲酯,聚乳酸,聚乳酸-羟基乙酸共聚物,聚乙醇酸,聚碳酸酯,环烯烃共聚物,聚乙烯基吡咯烷酮,聚乙烯醇,聚苯乙烯,聚甲基乙烯基醚-马来酸酐、透明质酸、壳聚糖、羟丙基纤维素、羟乙基纤维素、海藻酸钠和明胶中的任意一种或多种混合。
一些实施例中,可溶性聚合物微针针体2呈棱锥形或圆锥形或,所述任意一个微针针体2高度为100-1500μm,针体的底边直径为50-1000μm,针体机械强度为40-200MPa,其由针体集成阵列位于微针基座3上,阵列密度为每一平方厘米25-400根。
本发明一种用于皮肤疾病靶向诊疗的微针贴片的制备方法,包括以下步骤:
1)制备微针阵列模具:将PDMS(聚二甲基硅氧烷,Sylgard184)和固化剂按照10:1混合均匀,将混合物溶液倾倒在微针模板表面,在-0.08Mpa下抽真空除去混合溶液中的气泡,之后将混合物置于80℃烘箱加热固化3-4h取出,冷却后将固化的PDMS与微针模板分离,即得到PDMS微针阵列模具;
2)制备自组装纳米药物颗粒:将治疗性药物溶解到相应溶剂中,同时将近红外染料IR783溶于去离子水中,最后将药物溶液在搅拌状态下逐滴加入近红外染料IR783溶液中,室温搅拌30min,收集反应溶液高速离心,去除游离药物后得到的固体沉淀即为自组装纳米药物颗粒,随后将其溶解在PBS中;
3)制备可溶性聚合物溶液:将可溶性聚合物溶解到去离子水中得到可溶性聚合物溶液;
4)将步骤1)得到的PDMS微针阵列模具用氧等离子体处理之后,取适量步骤2)得到的纳米药物溶液滴在微针阴模表面进行离心处理,使纳米颗粒进入微针阴模的微孔中,取步骤3)得到的可溶性聚合物溶液注入微针阴模,在真空环境真空处理,干燥后将微针与阴模剥离,即得到载有粒径可控的自组装纳米药物的微针贴片。
步骤2)中所述自组装纳米药物颗粒溶液浓度为10-50mg/mL。
步骤3)中所述可溶性聚合物溶液浓度为100-1000mg/mL
步骤4)中,将步骤1)得到的PDMS微针阵列模具用氧等离子体处理之后,取适量步骤2)得到的纳米药物溶液滴在微针阴模表面进行离心处理,使纳米颗粒进入微针阴模的微孔中,取步骤3)得到的可溶性聚合物溶液注入微针阴模,于15℃下在-0.08MPa真空度的真空环境真空处理,然后在15℃下干燥12h后将微针与阴模剥离,即得到载有自组装纳米药物的微针贴片。
本发明微针贴片的应用方法:将所述载有自组装纳米药物颗粒的微针贴片垂直扎于皮肤患处,用力按压10-15min后取下。
一些实施例中,自组装纳米药物颗粒制备方法包括以下步骤:
1)配制治疗性药物溶液:将治疗性药物溶解在相应溶剂中,即得到治疗性药物溶液;
2)配制小分子近红外染料IR783溶液:将近红外染料IR783溶于去离子水中,即得到IR783溶液;
3)将步骤1)得到药物溶液在搅拌状态下逐滴加入步骤2)得到的小分子近红外染料IR783溶液中,室温搅拌30min,收集反应溶液后进行高速离心,去除游离药物后得到的固体沉淀即为自组装纳米药物颗粒。
一些实施例中,自组装纳米药物颗粒为雷帕霉素@IR783自组装纳米颗粒,所述可溶性聚合物溶液为透明质酸溶液,制备步骤如下:
1)制备微针阵列模具:将PDMS(聚二甲基硅氧烷,Sylgard184)和固化剂按照10:1混合均匀,将混合物溶液倾倒在四棱锥微针阵列模板表面,在-0.08Mpa下抽真空除去混合溶液中的气泡,之后将混合物置于80℃烘箱加热固化3-4h取出,冷却后将固化的PDMS与微针模板分离,即得到PDMS微针阵列模具;
2)制备雷帕霉素@IR783自组装纳米药物颗粒:将雷帕霉素溶解到相应溶剂中,同时将近红外染料IR783溶于去离子水中,最后将雷帕霉素溶液在搅拌状态下逐滴加入近红外染料IR783溶液中,室温搅拌30min,收集反应溶液高速离心,去除游离药物后得到的固体沉淀即为自组装纳米药物颗粒,随后将其溶解在PBS中;雷帕霉素浓度为20mg/mL;
3)制备透明质酸溶液:将透明质酸溶解到去离子水中得到透明质酸溶液,透明质酸浓度为500mg/mL;
4)将步骤1)得到的PDMS微针阵列模具用氧等离子体处理10s之后,取适量步骤2)得到的雷帕霉素@IR783自组装纳米药物颗粒溶液滴在微针阴模表面进行离心处理,使纳米颗粒进入微针阴模的微孔中,取步骤3)得到的透明质酸溶液注入微针阴模,在真空环境真空处理,干燥后将微针与阴模剥离,即得到载有雷帕霉素@IR783纳米颗粒的可用于皮肤疾病靶向诊疗的微针贴片。
实施例1
载有曲美替尼@IR783自组装纳米颗粒微针贴片的制备,包括以下步骤:
步骤1)制备微针阵列模具:将PDMS(聚二甲基硅氧烷,Sylgard184)和固化剂按照10:1混合均匀,将混合物溶液倾倒在四棱锥微针阵列模板表面,模板的规格如下:任意一个微针针头的高度为100μm,底径为100μm;相邻两个针头的尖端距离为200μm,在-0.08Mpa下抽真空除去混合溶液中的气泡,之后将混合物置于80℃烘箱加热固化3-4h取出,冷却后将固化的PDMS与微针模板分离,即得到PDMS微针阵列模具;
步骤2)制备曲美替尼@IR783自组装纳米药物颗粒:将20mg曲美替尼溶解在1mLDMSO中,同时将近红外染料1mg IR783溶于1mL去离子水中,最后将曲美替尼溶液在搅拌状态下逐滴加入近红外染料IR783溶液中,室温搅拌30min,收集反应溶液在20000g高速离心,去除游离药物后得到的固体沉淀即为曲美替尼@IR783药物颗粒,随后将其重悬在1mL在PBS中;
步骤3)制备聚乳酸溶液:将500mg聚乳酸溶解到去离子水中得到聚乳酸溶液,聚乳酸浓度为500mg/mL;
步骤4)将步骤1)得到的PDMS微针阵列模具用氧等离子体处理10s之后,取适量步骤2)得到的曲美替尼@IR783自组装纳米药物颗粒溶液滴在微针阴模表面进行离心处理,使纳米颗粒进入微针阴模的微孔中,取步骤3)得到的聚乳酸溶液注入微针阴模,在真空环境真空处理,干燥后将微针与阴模剥离,即得到载有曲美替尼@IR783纳米颗粒的可用于皮肤疾病靶向诊疗的微针贴片。
实施例2
载有索拉菲尼@IR783自组装纳米颗粒微针贴片的制备,包括以下步骤:
步骤1)制备微针阵列模具:将PDMS(聚二甲基硅氧烷,Sylgard184)和固化剂按照10:1混合均匀,将混合物溶液倾倒在四棱锥微针阵列模板表面,模板的规格如下:任意一个微针针头的高度为650μm,底径为200μm;相邻两个针头的尖端距离为500μm,在-0.08Mpa下抽真空除去混合溶液中的气泡,之后将混合物置于80℃烘箱加热固化3-4h取出,冷却后将固化的PDMS与微针模板分离,即得到PDMS微针阵列模具;
步骤2)制备索拉菲尼@IR783自组装纳米药物颗粒:将15mg索拉菲尼溶解在1mLDMSO中,同时将近红外染料1mg IR783溶于1mL去离子水中,最后将索拉菲尼溶液在搅拌状态下逐滴加入近红外染料IR783溶液中,室温搅拌30min,收集反应溶液在15000g高速离心,去除游离药物后得到的固体沉淀即为索拉菲尼@IR783药物颗粒,随后将其重悬在1mL在PBS中;
步骤3)制备聚乙烯基吡咯烷酮溶液:将300mg聚乙烯基吡咯烷酮溶解在去离子水中得到聚乙烯基吡咯烷酮溶液,聚乙烯基吡咯烷酮浓度为300mg/mL;
步骤4)将步骤1)得到的PDMS微针阵列模具用氧等离子体处理10s之后,取适量步骤2)得到的索拉菲尼@IR783自组装纳米药物颗粒溶液滴在微针阴模表面进行离心处理,使纳米颗粒进入微针阴模的微孔中,取步骤3)得到的聚乙烯基吡咯烷酮溶液注入微针阴模,在真空环境真空处理,干燥后将微针与阴模剥离,即得到载有索拉菲尼@IR783纳米颗粒的可用于皮肤疾病靶向诊疗的微针贴片。
实施例3
载有紫杉醇@IR783自组装纳米颗粒微针贴片的制备,包括以下步骤:
步骤1)制备微针阵列模具:将PDMS(聚二甲基硅氧烷,Sylgard184)和固化剂按照10:1混合均匀,将混合物溶液倾倒在四棱锥微针阵列模板表面,模板的规格如下:任意一个微针针头的高度为500μm,底径为300μm,相邻两个针头的尖端距离为500μm,在-0.08Mpa下抽真空除去混合溶液中的气泡,之后将混合物置于80℃烘箱加热固化3-4h取出,冷却后将固化的PDMS与微针模板分离,即得到PDMS微针阵列模具;
步骤2)制备紫杉醇@IR783自组装纳米药物颗粒:将50mg紫杉醇溶解在1mL DMSO中,同时将近红外染料1mg IR783溶于1mL去离子水中,最后将紫杉醇溶液在搅拌状态下逐滴加入近红外染料IR783溶液中,室温搅拌30min,收集反应溶液在20000g高速离心,去除游离药物后得到的固体沉淀即为紫杉醇@IR783药物颗粒,随后将其重悬在1mL在PBS中;
步骤3)制备聚乙烯醇溶液:将1000mg聚乙烯醇溶解到1mL去离子水中得到聚乙烯醇溶液,聚乙烯醇浓度为1000mg/mL;
步骤4)将步骤1)得到的PDMS微针阵列模具用氧等离子体处理10s之后,取适量步骤2)得到的紫杉醇@IR783自组装纳米药物颗粒溶液滴在微针阴模表面进行离心处理,使纳米颗粒进入微针阴模的微孔中,取步骤3)得到的聚乙烯醇溶液注入微针阴模,在真空环境真空处理,干燥后将微针与阴模剥离,即得到载有紫杉醇@IR783纳米颗粒的可用于皮肤疾病靶向诊疗的微针贴片。
实施例4
载有雷帕霉素@IR783自组装纳米颗粒微针贴片的制备,包括以下步骤:
步骤1)制备微针阵列模具:将PDMS(聚二甲基硅氧烷,Sylgard184)和固化剂按照10:1混合均匀,将混合物溶液倾倒在四棱锥微针阵列模板表面,模板的规格如下:任意一个微针针头的高度为1200μm,底径为800μm,相邻两个针头的尖端距离为1000μm,在-0.08Mpa下抽真空除去混合溶液中的气泡,之后将混合物置于80℃烘箱加热固化3-4h取出,冷却后将固化的PDMS与微针模板分离,即得到PDMS微针阵列模具;
步骤2)制备雷帕霉素@IR783自组装纳米药物颗粒:将20mg雷帕霉素溶解到1mLDMSO中,同时将近红外染料1mgIR783溶于1mL去离子水中,最后将雷帕霉素溶液在搅拌状态下逐滴加入近红外染料IR783溶液中,室温搅拌30min,收集反应溶液在15000g下高速离心,去除游离药物后得到的固体沉淀即为雷帕霉素@IR783药物颗粒,随后将其重悬在1mL PBS中,如图2所示,所制备的雷帕霉素@IR783纳米颗粒形态规则,呈球状结构。同时,如图3所示,雷帕霉素@IR783纳米颗粒的粒径维持在150nm左右,粒径分布均匀;
步骤3)制备透明质酸溶液:将500mg透明质酸溶解在1mL去离子水中得到透明质酸溶液,透明质酸浓度为500mg/mL;
步骤4)将步骤1)得到的PDMS微针阵列模具用氧等离子体处理10s之后,取适量步骤2)得到的雷帕霉素@IR783自组装纳米药物颗粒溶液滴在微针阴模表面进行离心处理,使纳米颗粒进入微针阴模的微孔中,取步骤3)得到的透明质酸溶液注入微针阴模,在真空环境真空处理,干燥后将微针与阴模剥离,即得到载有雷帕霉素@IR783纳米颗粒的可用于皮肤疾病靶向诊疗的微针贴片。将载有雷帕霉素@IR783自组装纳米颗粒的微针贴片分别置于皮肤镜和透射电子显微镜下进行观察,如图4、图5所示,微针针体均为较规整、均一的四棱锥阵列结构,针体尖端锋利,规整度高。
实施例5
载有雷帕霉素@IR783自组装纳米颗粒微针贴片处理咪喹莫特诱导的小鼠银屑病模型后,使用近红外二区成像仪器对银屑病小鼠进行影像学诊疗,探究纳米颗粒在小鼠皮肤中的代谢行为。
(1)取8周龄大小的BALB/c雌性小鼠10只,在10只小鼠右耳上连续七天于每天相同时间在该区域涂抹15mg的5%咪喹莫特乳膏,建立银屑病皮损模型。
(2)模型建立后,在皮损处贴敷载有雷帕霉素@IR783自组装纳米颗粒的微针贴片,每片扎10min至针头完全溶解。
(3)分别于扎完后的0h、1h、2h、3h、6h、9h、24h、36h进行小鼠活体成像,观察纳米颗粒在小鼠皮肤内的代谢行为。
结果:本发明所述的一种用于皮肤疾病靶向诊疗的微针贴片,内部载有雷帕霉素@IR783自组装纳米颗粒,如图6所示,该贴片能够在扎入小鼠皮肤后36h内持续检测出IR783荧光信号,侧面反映出通过该微针贴片的贴敷,可以实现对纳米药物代谢行为进行实时观察。同时,微针贴片包载的纳米颗粒中的雷帕霉素也能够作为治疗性药物进行疾病的病情控制。能够实现对疾病的诊断和治疗的双重效果。本发明首次解决了皮肤疾病的靶向诊疗,采用微针递药系统实现精准快速的透皮给药,大大提高了药物递送剂量,也高效地实现皮肤疾病的诊疗一体化。
本领域的技术人员容易理解,以上所述仅为本发明的较佳实施例而已,并不用以限制本发明,凡在本发明的精神和原则之内所作的任何修改、等同替换和改进等,均应包含在本发明的保护范围之内。
Claims (10)
1.一种微针贴片,其特征在于,该微针贴片包括基座和聚合物针体,所述聚合物针体以阵列形式位于基座上,形成所述聚合物针体的聚合物能溶于水,所述聚合物针体的针尖部分分散有纳米药物颗粒,所述纳米药物颗粒为药物与荧光分子自组装形成的纳米粒子。
2.如权利要求1所述的微针贴片,其特征在于,所述药物为曲美替尼、索拉菲尼、紫杉醇、雷帕霉素、佛维司群和恩杂鲁胺中的至少一种;所述荧光分子为近红外染料IR783。
3.如权利要求1所述的微针贴片,其特征在于,形成所述聚合物针体的聚合物为聚甲基丙烯酸甲酯、聚乳酸、聚乳酸与羟基乙酸共聚物、聚乙醇酸、聚碳酸酯、环烯烃共聚物、聚乙烯基吡咯烷酮、聚乙烯醇、聚苯乙烯、聚甲基乙烯基醚与马来酸酐共聚物、透明质酸、壳聚糖、羟丙基纤维素、羟乙基纤维素、海藻酸钠和明胶中的至少一种。
4.如权利要求1或3所述的微针贴片,其特征在于,所述聚合物针体的密度为25-400根/平方厘米基底;所述聚合物针体的高度为100-1500μm;所述微针贴片的聚合物针体阵列的机械强度为40-200MPa。
5.如权利要求1所述的微针贴片,其特征在于,所述微针贴片的聚合物针体阵列含有纳米药物颗粒1-500μg。
6.如权利要求1所述的微针贴片,其特征在于,所述聚合物针体呈圆锥形或棱锥形。
7.如权利要求6所述的微针贴片,其特征在于,圆锥形针体的底边直径为50-1000μm。
8.如权利要求1-7任一所述的微针贴片的制备方法,其特征在于,包括以下步骤:
(1)将微针阵列阴模用氧等离子体处理,使微针阵列阴模表面亲水;将纳米药物的溶液滴在微针阵列阴模表面进行离心处理,使纳米药物颗粒进入微针阵列阴模的微孔中;所述纳米药物为药物与荧光分子自组装形成的纳米粒子;
(2)将能溶于水的聚合物溶液注入微针阵列阴模,并进行抽真空处理,然后进行干燥,干燥后将微针与阴模剥离,即得到装载有纳米药物颗粒的微针贴片;
优选地,所述药物与荧光分子自组装形成的纳米粒子具体制备方法为:将药物和荧光分子分别溶解,得到药物溶液和荧光分子溶液,将所述药物溶液逐滴加入到荧光分子溶液中,并不断搅拌,离心去除游离药物后得到的固体沉淀即为药物与荧光分子自组装形成的纳米粒子。
9.如权利要求8所述的微针贴片的制备方法,其特征在于,步骤(1)中所述纳米药物溶液的浓度为10-50mg/mL;步骤(2)中所述聚合物溶液的浓度为100-1000mg/mL。
10.如权利要求1-7任一所述的微针贴片用于制备皮肤疾病靶向诊疗贴片的应用。
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