CN111544756A - 一种载光敏剂的无痛可溶性微针和微针阵列及制备方法 - Google Patents
一种载光敏剂的无痛可溶性微针和微针阵列及制备方法 Download PDFInfo
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- CN111544756A CN111544756A CN201910231034.4A CN201910231034A CN111544756A CN 111544756 A CN111544756 A CN 111544756A CN 201910231034 A CN201910231034 A CN 201910231034A CN 111544756 A CN111544756 A CN 111544756A
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- microneedle
- polydimethylsiloxane
- photosensitizer
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Abstract
一种载光敏剂的无痛可溶性微针,所述微针包括基座、位于所述基座上的可溶性聚合物针体以及载有光敏剂和麻醉剂的针尖;所述基座、针体以及针尖为一体成型。一种载光敏剂的无痛可溶性微针阵列,所述微针阵列由1根以上的微针组成。一种载光敏剂的无痛可溶性微针阵列的制备方法,包括以下步骤:1)聚二甲基硅氧烷(PDMS)模具板的制备;2)激光刻蚀聚二甲基硅氧烷(PDMS)微针阴模;3)含有光敏剂和麻醉剂的可溶性聚合物水溶液的制备;4)微针阵列的制备。本发明可解决光动力治疗中给药方式不合理、患者在光动力治疗中需使用止痛措施的技术问题,同时解决了载光敏剂的无痛可溶性微针阵列的制备问题。
Description
技术领域
本发明属于生物医用材料领域,更具体地,涉及一种载光敏剂的无痛可溶性微针和微针阵列及制备方法。
背景技术
光动力治疗是一种通过在特定波长光波的作用下使靶细胞中内源性或外源性光敏剂与氧发生一系列光化学反应,生成单态氧、氧离子、过氧化物、含氧自由基等活性氧,诱导细胞死亡,从而有选择性地破坏靶组织的治疗方法然而,一方面,光动力的治疗过程会给人带来较为严重的疼痛,44%的患者在光动力治疗中需使用止痛措施。另一方面,目前光动力治疗中光敏剂的给药方式多为外用(如5-ALA)或静脉注射(如海姆泊芬)。光敏剂外用常以溶液、软膏、凝胶等剂型外敷,然而由于皮肤角质层的屏障作用,无论上述何种剂型,均存在透皮效率低、药物分布不均、需要以高浓度光敏剂长时间敷药等问题,导致治疗效果不佳,患者依从性差。而静脉注射方式存在药物利用率低、靶向性差、副作用大等问题,不利于光动力治疗的进行。因此光动力治疗如何给药是一项亟待解决的课题。
微针是由硅、金属、聚合物等制成的长度为25–2000μm、针尖呈锥形的三维阵列。微针是生物医药领域里的一种新型微创给药工具,可以透过皮肤表皮和真皮层,从而增强皮肤给药效果。微针以其高效、安全、无痛感等优势在经皮给药领域中得到了广泛的应用。
可溶性微针阵列是以可溶性、可降解高分子材料制备的微针阵列。在给药过程中,药物在可溶性微针阵列中高分子材料溶解或者降解后被释放出来。可溶性微针阵列的制备方法简单温和、安全性好、载药效率高,是一类非常有前景的给药方式。
因此,将微针应用于光动力治疗是一项有意义的课题。
发明内容
本发明的目的在于提供一种载光敏剂的无痛可溶性微针和微针阵列及制备方法,解决光动力治疗中给药方式不合理、患者在光动力治疗中需使用止痛措施的技术问题,同时解决了载光敏剂的无痛可溶性微针阵列的制备问题。
本发明采用以下技术手段:
一种载光敏剂的无痛可溶性微针,所述微针包括基座、位于所述基座上的可溶性聚合物针体以及载有光敏剂和麻醉剂的针尖;所述基座、针体以及针尖为一体成型。
所述针体具备良好的生物相容性。
所述光敏剂为卟啉类分子、卟啉类分子前体、二氢卟吩类分子、细菌卟吩类分子、三碳菁类分子、酞菁类分子、吩噻嗪类分子、玫瑰红类分子、方酸菁类分子、硼-二吡咯亚甲基类染料、芴酮类分子、过渡金属化合物、天然活性产物、竹红菌素、核黄素、姜黄素、合成染料或载光敏剂纳米粒子中的一种或多种。
所述卟啉类分子及卟啉类分子前体包括5-氨基酮戊酸(5-ALA)及其酯化物,所述二氢卟吩类分子包括二氢卟吩e6(Ce6),所述三碳菁类分子包括吲哚箐绿(ICG),所述天然活性产物包括金丝桃素。
所述麻醉剂为普鲁卡因、氯普鲁卡因、利多卡因、碳酸利多卡因、丁卡因、布比卡因、左旋布比卡因、罗哌卡因中的一种或多种组合。
所述可溶性聚合物包括透明质酸、乙烯吡咯烷酮-乙酸乙烯酯共聚物、聚乙烯醇、聚乙烯吡咯烷酮、明胶、丝素蛋白、蚕丝蛋白、糊精、羧甲基纤维素、羟丙基纤维素、羟丙基甲基纤维素、软骨硫磺素、葡聚糖、海藻酸钠、支链淀粉、麦芽糖、聚γ-谷氨酸中的一种或多种。
一种载光敏剂的无痛可溶性微针阵列,所述微针阵列由1根以上的微针组成,所述可溶性微针呈棱锥形、圆锥形或类锥形,所述微针的长度为100–5000μm,底径为50–800μm,相邻所述微针针尖间距为100–5000μm,所载光敏剂的含量为1-1000μg/cm2微针阵列。
一种载光敏剂的无痛可溶性微针阵列的制备方法,包括以下步骤:
1)聚二甲基硅氧烷(PDMS)模具板的制备:将聚二甲基硅氧烷(聚二甲基硅氧烷(PDMS))和固化剂置于烧杯中,搅拌均匀,然后置于超声清洗机中除去气泡,然后将上述混合物倒在一次性培养皿中,平铺;将培养皿放入恒温真空干燥箱,抽真空以除尽所述混合物中气泡,加热,使聚二甲基硅氧烷(PDMS)固化;冷却后将固化的聚二甲基硅氧烷(PDMS)从培养皿剥离,即得到聚二甲基硅氧烷(PDMS)模具板;
2)激光刻蚀聚二甲基硅氧烷(PDMS)微针阴模:用一体式光纤二氧化碳激光打标机设置参数刻蚀聚二甲基硅氧烷(PDMS)模具板,去除材料多余材料得到聚二甲基硅氧烷(PDMS)微针阵列阴模;
3)将光敏剂、麻醉剂和可溶性聚合物均匀分散到超纯水中得到含有光敏剂和麻醉剂的可溶性聚合物水溶液;
4)将步骤2)得到的聚二甲基硅氧烷(PDMS)微针阵列阴模用氧等离子体处理后,取步骤3)得到的含有光敏剂和麻醉剂的可溶性聚合物水溶液涂在该聚二甲基硅氧烷(PDMS)微针阵列阴模的表面,在真空环境中使药物进入模具尖端,回收多余药物;在上述已载有光敏剂和麻醉剂的聚二甲基硅氧烷(PDMS)模具上加入可溶性聚合物溶液,在真空下使可溶性聚合物溶液填满模具;静置后干燥,随后将所述聚二甲基硅氧烷(PDMS)微针阵列阴模剥离。
所述可溶性聚合物为透明质酸,所述光敏剂为5-ALA,所述麻醉剂为利多卡因,所述微针阵列的制备方法,包括以下步骤:
1)聚二甲基硅氧烷(PDMS)模具板的制备:将聚二甲基硅氧烷(PDMS)和固化剂按质量比10:1置于烧杯中,搅拌5min左右,然后置于超声清洗机中约10min,除去气泡,然后将上述混合物倒在一次性培养皿中,使其厚度约为3-4mm;将所述培养皿放入恒温真空干燥箱,抽真空至真空度为-0.08MPa以除尽所述混合物中气泡;80℃下加热2h使聚二甲基硅氧烷(PDMS)固化;冷却后将固化的聚二甲基硅氧烷(PDMS)与剥离,即得到聚二甲基硅氧烷(PDMS)模具板。
2)激光刻蚀聚二甲基硅氧烷(PDMS)微针阴模:用一体式光纤CO2激光打标机设置参数刻蚀聚二甲基硅氧烷(PDMS)模具板,制备聚二甲基硅氧烷(PDMS)微针阴模,使该微针矩阵模对应的微针贴片含10*10共100根微针,针高830μm,针底宽310μm,针心间距700μm。
3)将5-ALA、利多卡因和透明质酸均匀分散到超纯水中得到含有5-ALA和利多卡因的透明质酸水溶液,所述透明质酸水溶液中5-ALA的浓度为20%,利多卡因浓度为2%,所述透明质酸的浓度为300mg/mL,所述透明质酸的数均分子量为10kDa;
4)将所述步骤2得到的聚二甲基硅氧烷(PDMS)微针阵列模板用氧等离子体处理1min,然后,取所述步骤3)得到的所述含有5-ALA和利多卡因的透明质酸水溶液60mg涂在该聚二甲基硅氧烷(PDMS)微针阵列模板的表面,25℃下在-0.08MPa真空度的真空环境中使药物进入模具尖端,回收多余药物;在上述已载有5-ALA和利多卡因的聚二甲基硅氧烷(PDMS)模具上加入300mg/mL的透明质酸溶液,在真空下使透明质酸溶液填满模具;放置10min后取出,然后在25℃下干燥12h,随后将所述聚二甲基硅氧烷(PDMS)微针阵列模板剥离,即得到载有5-ALA和利多卡因的透明质酸微针阵列。
本发明的有益效果是:
1)通过将光敏剂和麻醉剂负载在可溶性微针中,可有效地穿透皮肤角质层,从而将光敏剂和麻醉剂直接递送至皮损部位。光敏剂和麻醉剂在可溶性聚合物溶解后保留在患处,明显改善了光敏剂和和麻醉剂的透皮效率,使光敏剂和麻醉剂在患处均匀分布。该类递送方式处理时间短,药物利用率高,且由于是局部给药,避免了毒副作用的发生,并使得照光过程中患者的疼痛大大减轻。
2)本发明通过将光敏剂和麻醉剂载入可溶性微针之中,将药物精准快速地递送至皮损部位,克服了传统的通过溶液、软膏或凝胶给药的光动力治疗的敷药时间长、光敏剂和麻醉剂透皮效率低、分布不均匀等弊端,能以更少光敏剂和麻醉剂剂量达到更佳的疗效。
附图说明
图1:本发明负载5-ALA和利多卡因的可溶性透明质酸微针示意图;
图2:本发明微针阵列中包含的微针个体结构示意图;
图3:本发明微针阵列的结构示意图。
附图编号:1-基座,2-针体,3-针尖。
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。
一种载光敏剂的无痛可溶性微针,所述微针包括基座1、位于所述基座1上的可溶性聚合物针体2以及载有光敏剂和麻醉剂的针尖3;所述基座1、针体2以及针尖3为一体成型。
所述针体2具备良好的生物相容性。
所述光敏剂为卟啉类分子、卟啉类分子前体、二氢卟吩类分子、细菌卟吩类分子、三碳菁类分子、酞菁类分子、吩噻嗪类分子、玫瑰红类分子、方酸菁类分子、硼-二吡咯亚甲基类染料、芴酮类分子、过渡金属化合物、天然活性产物、竹红菌素、核黄素、姜黄素、合成染料或载光敏剂纳米粒子中的一种或多种。
所述卟啉类分子及卟啉类分子前体包括5-氨基酮戊酸(5-ALA)及其酯化物,所述二氢卟吩类分子包括二氢卟吩e6(Ce6),所述三碳菁类分子包括吲哚箐绿(ICG),所述天然活性产物包括金丝桃素。
所述麻醉剂为普鲁卡因、氯普鲁卡因、利多卡因、碳酸利多卡因、丁卡因、布比卡因、左旋布比卡因、罗哌卡因中的一种或多种组合。
所述可溶性聚合物包括透明质酸、乙烯吡咯烷酮-乙酸乙烯酯共聚物、聚乙烯醇、聚乙烯吡咯烷酮、明胶、丝素蛋白、蚕丝蛋白、糊精、羧甲基纤维素、羟丙基纤维素、羟丙基甲基纤维素、软骨硫磺素、葡聚糖、海藻酸钠、支链淀粉、麦芽糖、聚γ-谷氨酸中的一种或多种。
一种载光敏剂的无痛可溶性微针阵列,所述微针阵列由1根以上的微针组成,所述可溶性微针呈棱锥形、圆锥形或类锥形,所述微针的长度为100–5000μm,底径为50–800μm,相邻所述微针针尖间距为100–5000μm,所载光敏剂的含量为1-1000μg/cm2微针阵列。
一种载光敏剂的无痛可溶性微针阵列的制备方法,包括以下步骤:
1)聚二甲基硅氧烷(PDMS)模具板的制备:将聚二甲基硅氧烷(聚二甲基硅氧烷(PDMS))和固化剂置于烧杯中,搅拌均匀,然后置于超声清洗机中除去气泡,然后将上述混合物倒在一次性培养皿中,平铺;将培养皿放入恒温真空干燥箱,抽真空以除尽所述混合物中气泡,加热,使聚二甲基硅氧烷(PDMS)固化;冷却后将固化的聚二甲基硅氧烷(PDMS)从培养皿剥离,即得到聚二甲基硅氧烷(PDMS)模具板;
2)激光刻蚀聚二甲基硅氧烷(PDMS)微针阴模:用一体式光纤二氧化碳激光打标机设置参数刻蚀聚二甲基硅氧烷(PDMS)模具板,去除材料多余材料得到聚二甲基硅氧烷(PDMS)微针阵列阴模;
3)含有光敏剂和麻醉剂的可溶性聚合物水溶液的制备:将光敏剂、麻醉剂和可溶性聚合物均匀分散到超纯水中得到含有光敏剂和麻醉剂的可溶性聚合物水溶液;
4)将步骤2)得到的聚二甲基硅氧烷(PDMS)微针阵列阴模用氧等离子体处理后,取步骤3)得到的含有光敏剂和麻醉剂的可溶性聚合物水溶液涂在该聚二甲基硅氧烷(PDMS)微针阵列阴模的表面,在真空环境中使药物进入模具尖端,回收多余药物;在上述已载有光敏剂和麻醉剂的聚二甲基硅氧烷(PDMS)模具上加入可溶性聚合物溶液,在真空下使可溶性聚合物溶液填满模具;静置后干燥,随后将所述聚二甲基硅氧烷(PDMS)微针阵列阴模剥离。
所述可溶性聚合物为透明质酸,所述光敏剂为5-ALA,所述麻醉剂为利多卡因,所述微针阵列的制备方法,包括以下步骤:
1)聚二甲基硅氧烷(PDMS)模具板的制备:将聚二甲基硅氧烷(PDMS)和固化剂按质量比10:1置于烧杯中,搅拌5min左右,然后置于超声清洗机中约10min,除去气泡,然后将上述混合物倒在一次性培养皿中,使其厚度约为3-4mm;将所述培养皿放入恒温真空干燥箱,抽真空至真空度为-0.08MPa以除尽所述混合物中气泡;80℃下加热2h使聚二甲基硅氧烷(PDMS)固化;冷却后将固化的聚二甲基硅氧烷(PDMS)与剥离,即得到聚二甲基硅氧烷(PDMS)模具板。
2)激光刻蚀聚二甲基硅氧烷(PDMS)微针阴模:用一体式光纤CO2激光打标机设置参数刻蚀聚二甲基硅氧烷(PDMS)模具板,制备聚二甲基硅氧烷(PDMS)微针阴模,使该微针矩阵模对应的微针贴片含10*10共100根微针,针高830μm,针底宽310μm,针心间距700μm。
3)将5-ALA、利多卡因和透明质酸均匀分散到超纯水中得到含有5-ALA和利多卡因的透明质酸水溶液,所述透明质酸水溶液中5-ALA的浓度为20%,利多卡因浓度为2%,所述透明质酸的浓度为300mg/mL,所述透明质酸的数均分子量为10kDa;
4)将所述步骤2得到的聚二甲基硅氧烷(PDMS)微针阵列模板用氧等离子体处理1min,然后,取所述步骤3)得到的所述含有5-ALA和利多卡因的透明质酸水溶液60mg涂在该聚二甲基硅氧烷(PDMS)微针阵列模板的表面,25℃下在-0.08MPa真空度的真空环境中使药物进入模具尖端,回收多余药物;在上述已载有5-ALA和利多卡因的聚二甲基硅氧烷(PDMS)模具上加入300mg/mL的透明质酸溶液,在真空下使透明质酸溶液填满模具;放置10min后取出,然后在25℃下干燥12h,随后将所述聚二甲基硅氧烷(PDMS)微针阵列模板剥离,即得到载有5-ALA和利多卡因的透明质酸微针阵列。
所述光敏剂为在特定波长光波的照射下其本身或代谢产物能发生光动力反应生成活性氧的物质。
本发明可溶性微针应用于光动力治疗的步骤包括:(1)将所述载光敏剂的可溶性微针扎于患处,按压一定时间至微针针尖溶解后取下;(2)一定时间后对施针处给予特定波长激发光照射。按压时间为1s至10min,从开始按压到给予激发光照射的时间间隔为10min至24h。
本发明的载光敏剂无痛可溶性微针可应用于光动力治疗,其适应症包括如下几种:
(1)良性肿瘤及癌前病变,如脂溢性角化、日光性角化、鲍恩样丘疹病、角化棘皮瘤、增殖性红斑、婴幼儿血管瘤和血管畸形等;
(2)皮肤浅表感染:病毒感染(如尖锐湿疣、寻常疣、扁平疣等)、细菌感染、真菌感染、寄生虫感染(如皮肤利什曼病等);
(3)皮脂腺相关疾病:如痤疮、头部脓肿性穿掘性毛囊周围炎、化脓性汗腺炎、皮脂溢出等;
(4)皮肤恶性肿瘤:如黑素瘤、皮肤淋巴瘤、基底细胞癌、鲍温病、皮肤鳞状细胞癌、乳房外Paget病;
(5)其它皮肤病:如扁平苔藓、硬化性萎缩性苔藓、硬皮病、银屑病、皮肤光老化、光线性唇炎等;
(6)皮肤浅表肿瘤和感染的检测。
实施例1:负载5-ALA和利多卡因的可溶性透明质酸微针的制备
1、聚二甲基硅氧烷(PDMS)模具板的制备:将聚二甲基硅氧烷(聚二甲基硅氧烷(PDMS))和固化剂按质量比10:1置于烧杯中,搅拌5min左右,然后置于超声清洗机中约10min,除去气泡,然后将上述混合物倒在一次性培养皿中,使其厚度约为3-4mm。将培养皿放入恒温真空干燥箱,抽真空至真空度为-0.08MPa以除尽所述混合物中气泡。80℃下加热2h使聚二甲基硅氧烷(PDMS)固化;冷却后将固化的聚二甲基硅氧烷(PDMS)与剥离,即得到聚二甲基硅氧烷(PDMS)模具板。
2、激光刻蚀聚二甲基硅氧烷(PDMS)微针阴模:用一体式光纤CO2激光打标机设置参数刻蚀聚二甲基硅氧烷(PDMS)模具板,制备聚二甲基硅氧烷(PDMS)微针阴模,使该微针矩阵模对应的微针贴片含10*10共100根微针,针高830μm,针底宽310μm,针心间距700μm。
3、将5-ALA、利多卡因和透明质酸均匀分散到超纯水中得到含有5-ALA和利多卡因的透明质酸水溶液,所述透明质酸水溶液中5-ALA的浓度为20%,利多卡因浓度为2%,所述透明质酸的浓度为300mg/mL,所述透明质酸的数均分子量为10kDa;
4、将所述步骤2得到的聚二甲基硅氧烷(PDMS)微针阵列模板用氧等离子体处理1min,然后,取步骤3得到的所述含有5-ALA和利多卡因的透明质酸水溶液60mg涂在该聚二甲基硅氧烷(PDMS)微针阵列模板的表面,25℃下在-0.08MPa真空度的真空环境中使药物进入模具尖端,回收多余药物;在上述已载有5-ALA和利多卡因的聚二甲基硅氧烷(PDMS)模具上加入300mg/mL的透明质酸溶液,在真空下使透明质酸溶液填满模具;放置10min后取出,然后在25℃下干燥12h,随后将所述聚二甲基硅氧烷(PDMS)微针阵列模板剥离,即得到载有5-ALA和利多卡因的透明质酸微针阵列(如图1)。
实施例2–6:不同参数的无痛可溶性光动力治疗微针
此外,按照实施例1的方法,通过调整聚二甲基硅氧烷(PDMS)微针阴模的结构和光敏剂溶液浓度,得到了如表1所示的具有多种不同参数的微针。
使用本发明实施例1的方法制备的具有不同长度、底径、相邻针尖间距、光敏剂类型、光敏剂含量的无痛可溶性光动力治疗微针,结果如下表:
治疗时按压时间为1s至10min,从开始按压到给予激发光照射的时间间隔为10min至24h。
载光敏剂的可溶性微针在检测肿瘤中的应用
1、按照实施例1方法制备载5-ALA的可溶性透明质酸微针(含10*10共100根微针,针高830μm,针底宽310μm,针心间距700μm);
2、将载5-ALA的可溶性透明质酸微针扎入病灶所在部位,按压5min后取下;
3、3-4h后使用405-408nm波长的蓝光照射病灶部位,肿瘤组织中选择性集聚的原卟啉(PpIX)可在该波长激发光下发出633-637nm红色荧光,而正常组织不发光,可依此鉴别正常组织与肿瘤组织。
实验证明,本发明相比起传统光敏剂给药方式具有敷药时间短、透皮效率高、精准递送、安全无毒、便于储存、疗效显著等优点,且解决了光动力治疗中因疼痛需要加麻醉措施的问题,在光动力治疗领域具有广阔的应用前景。
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 (9)
1.一种载光敏剂的无痛可溶性微针,其特征在于,所述微针包括基座、位于所述基座上的可溶性聚合物针体以及载有光敏剂和麻醉剂的针尖;所述基座、针体以及针尖为一体成型。
2.如权利要求1所述的一种载光敏剂的无痛可溶性微针,其特征在于,所述针体具备良好的生物相容性。
3.如权利要求1所述的一种载光敏剂的无痛可溶性微针,其特征在于,所述光敏剂为卟啉类分子、卟啉类分子前体、二氢卟吩类分子、细菌卟吩类分子、三碳菁类分子、酞菁类分子、吩噻嗪类分子、玫瑰红类分子、方酸菁类分子、硼-二吡咯亚甲基类染料、芴酮类分子、过渡金属化合物、天然活性产物、竹红菌素、核黄素、姜黄素、合成染料或载光敏剂纳米粒子中的一种或多种。
4.如权利要求3所述的一种载光敏剂的无痛可溶性微针,其特征在于,所述卟啉类分子及卟啉类分子前体包括5-氨基酮戊酸(5-ALA)及其酯化物,所述二氢卟吩类分子包括二氢卟吩e6(Ce6),所述三碳菁类分子包括吲哚箐绿(ICG),所述天然活性产物包括金丝桃素。
5.如权利要求1所述的一种载光敏剂的无痛可溶性微针,其特征在于,所述麻醉剂为普鲁卡因、氯普鲁卡因、利多卡因、碳酸利多卡因、丁卡因、布比卡因、左旋布比卡因、罗哌卡因中的一种或多种组合。
6.如权利要求1所述的一种载光敏剂的无痛可溶性微针,其特征在于,所述可溶性聚合物包括透明质酸、乙烯吡咯烷酮-乙酸乙烯酯共聚物、聚乙烯醇、聚乙烯吡咯烷酮、明胶、丝素蛋白、蚕丝蛋白、糊精、羧甲基纤维素、羟丙基纤维素、羟丙基甲基纤维素、软骨硫磺素、葡聚糖、海藻酸钠、支链淀粉、麦芽糖、聚γ-谷氨酸中的一种或多种。
7.一种载光敏剂的无痛可溶性微针阵列,其特征在于,所述微针阵列由1根以上的微针组成,所述可溶性微针呈棱锥形、圆锥形或类锥形,所述微针的长度为100–5000μm,底径为50–800μm,相邻所述微针针尖间距为100–5000μm,所载光敏剂的含量为1-1000μg/cm2微针阵列。
8.一种载光敏剂的无痛可溶性微针阵列的制备方法,其特征在于,包括以下步骤:
1)聚二甲基硅氧烷(PDMS)模具板的制备:将聚二甲基硅氧烷(聚二甲基硅氧烷(PDMS))和固化剂置于烧杯中,搅拌均匀,然后置于超声清洗机中除去气泡,然后将上述混合物倒在一次性培养皿中,平铺;将培养皿放入恒温真空干燥箱,抽真空以除尽所述混合物中气泡,加热,使聚二甲基硅氧烷(PDMS)固化;冷却后将固化的聚二甲基硅氧烷(PDMS)从培养皿剥离,即得到聚二甲基硅氧烷(PDMS)模具板;
2)激光刻蚀聚二甲基硅氧烷(PDMS)微针阴模:用一体式光纤二氧化碳激光打标机设置参数刻蚀聚二甲基硅氧烷(PDMS)模具板,去除材料多余材料得到聚二甲基硅氧烷(PDMS)微针阵列阴模;
3)含有光敏剂和麻醉剂的可溶性聚合物水溶液的制备:将光敏剂、麻醉剂和可溶性聚合物均匀分散到超纯水中得到含有光敏剂和麻醉剂的可溶性聚合物水溶液;
4)将步骤2)得到的聚二甲基硅氧烷(PDMS)微针阵列阴模用氧等离子体处理后,取步骤3)得到的含有光敏剂和麻醉剂的可溶性聚合物水溶液涂在该聚二甲基硅氧烷(PDMS)微针阵列阴模的表面,在真空环境中使药物进入模具尖端,回收多余药物;在上述已载有光敏剂和麻醉剂的聚二甲基硅氧烷(PDMS)模具上加入可溶性聚合物溶液,在真空下使可溶性聚合物溶液填满模具;静置后干燥,随后将所述聚二甲基硅氧烷(PDMS)微针阵列阴模剥离。
9.如权利要求8所述的一种载光敏剂的无痛可溶性微针阵列的制备方法,其特征在于,所述可溶性聚合物为透明质酸,所述光敏剂为5-ALA,所述麻醉剂为利多卡因,所述微针阵列的制备方法,包括以下步骤:
1)聚二甲基硅氧烷(PDMS)模具板的制备:将聚二甲基硅氧烷(PDMS)和固化剂按质量比10:1置于烧杯中,搅拌5min左右,然后置于超声清洗机中约10min,除去气泡,然后将上述混合物倒在一次性培养皿中,使其厚度约为3-4mm;将所述培养皿放入恒温真空干燥箱,抽真空至真空度为-0.08MPa以除尽所述混合物中气泡;80℃下加热2h使聚二甲基硅氧烷(PDMS)固化;冷却后将固化的聚二甲基硅氧烷(PDMS)与剥离,即得到聚二甲基硅氧烷(PDMS)模具板。
2)激光刻蚀聚二甲基硅氧烷(PDMS)微针阴模:用一体式光纤CO2激光打标机设置参数刻蚀聚二甲基硅氧烷(PDMS)模具板,制备聚二甲基硅氧烷(PDMS)微针阴模,使该微针矩阵模对应的微针贴片含10*10共100根微针,针高830μm,针底宽310μm,针心间距700μm。
3)将5-ALA、利多卡因和透明质酸均匀分散到超纯水中得到含有5-ALA和利多卡因的透明质酸水溶液,所述透明质酸水溶液中5-ALA的浓度为20%,利多卡因浓度为2%,所述透明质酸的浓度为300mg/mL,所述透明质酸的数均分子量为10kDa;
4)将所述步骤2)得到的聚二甲基硅氧烷(PDMS)微针阵列模板用氧等离子体处理1min,然后,取所述步骤3)得到的所述含有5-ALA和利多卡因的透明质酸水溶液60mg涂在该聚二甲基硅氧烷(PDMS)微针阵列模板的表面,25℃下在-0.08MPa真空度的真空环境中使药物进入模具尖端,回收多余药物;在上述已载有5-ALA和利多卡因的聚二甲基硅氧烷(PDMS)模具上加入300mg/mL的透明质酸溶液,在真空下使透明质酸溶液填满模具;放置10min后取出,然后在25℃下干燥12h,随后将所述聚二甲基硅氧烷(PDMS)微针阵列模板剥离,即得到载有5-ALA和利多卡因的透明质酸微针阵列。
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