CN116350925A - 一种光热抗菌微针及其制备方法 - Google Patents
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Abstract
本发明涉及一种光热抗菌微针及其制备方法,首先配制微针衬底溶液:采用水溶性高分子聚合物溶解得到;配制微针针尖溶液:采用天然材料聚合物溶解得到;制备FeTAP纳米酶:制备PVP溶液,向PVP溶液中加入FeCl3、单宁酸溶液,透析、冷冻干燥得到FeTAP纳米酶;制备光热抗菌微针:将FeTAP纳米酶溶解于微针针尖溶液中,加入到微针模板中,充分干燥;然后将微针衬底溶液加入到微针模板表面,再次充分干燥后,得到光热抗菌微针。该抗菌微针具有光热效应,能实现更好的局部的、持久的、高效抗菌给药,可用于组织工程及再生医学等技术领域。
Description
技术领域
本发明涉及医学材料领域,具体涉及一种光热抗菌微针及其制备方法。
背景技术
细菌性角膜炎又称细菌性角膜溃疡,是一种由细菌感染引起的角膜炎症,如葡萄球菌、链球菌、链球菌和假单胞菌。细菌性角膜炎的治疗不当或不有效,可能导致角膜穿孔、眼内感染,最终导致不可逆的视力损伤和失明。抗生素眼药水是治疗细菌性角膜炎最广泛使用的疗法。然而,由于角膜存在独特的解剖和生理结构特征,如上皮细胞中的紧密连接,眼药水无法渗透到角膜中,导致药物的爆裂释放,抵抗时间短,局部给药后生物利用度差。此外,抗生素的滥用导致了耐抗生素细菌的出现,为基于抗生素的治疗前景蒙上了阴影。相比之下,基于传统皮下注射针的眼内注射可以穿透表面屏障,改善局部给药,耐药性延长,而病人的依从性却很差,因为疼痛、频繁的就诊要求以及感染和出血的风险。因此,在治疗细菌性角膜炎方面,局部的、持久的、高效的抗菌剂的眼部给药,以及良好的患者依从性,是非常值得期待的。
纳米酶表示具有模拟酶活性的纳米材料。由于纳米酶易于制备,具有规范的催化活性,稳定性高,成本效益高,且易于处理,因此在各种应用中,纳米酶已成为天然酶的有前途的替代品。具体来说,由铁离子和多元酚组装的纳米酶表现出良好的生物相容性、生物降解性、pH值依赖性催化活性和活性氧(ROS)形成或清除能力。然而,如何有效和局部地将这些纳米酶输送到眼球表面仍然是一个挑战。另外,微针(MNs)是一种微米级的小针阵列,已被广泛用于穿透表皮,实现无痛、无创、高效的经皮给药。药物、功能性细胞因子、干细胞、蛋白质、二维材料和金属有机框架材料已被纳入MNs内,用于各种治疗目的。
发明内容
本发明的目的是提供一种光热抗菌微针及其制备方法,该抗菌微针具有光热效应,能实现更好的局部的、持久的、高效抗菌给药。
为实现上述目的,本发明提供的技术方案是:
一种光热抗菌微针的制备方法,包括以下步骤:
(1)配制微针衬底溶液:采用水溶性高分子聚合物溶解得到微针衬底溶液,微针衬底溶液用于制备光热抗菌微针的衬底;
(2)配制微针针尖溶液:采用天然材料聚合物溶解得到微针针尖溶液,微针针尖溶液用于制备光热抗菌微针的针尖;
(3)制备FeTAP纳米酶:制备聚乙烯吡咯烷酮PVP溶液,向PVP溶液中加入FeCl3,搅拌后加入单宁酸TA溶液,继续搅拌后进行透析、冷冻干燥得到FeTAP纳米酶;
(4)制备光热抗菌微针:将步骤(3)制备的FeTAP纳米酶溶解于步骤(2)配制的微针针尖溶液中,加入到微针模板中,充分干燥;然后将步骤(1)中配制的微针衬底溶液加入到微针模板表面,再次充分干燥后,得到光热抗菌微针。
为优化上述技术方案,采取的具体措施还包括:
步骤(1)中,水溶性高分子聚合物选自聚乙烯醇(PVA)、聚氧化乙烯(PEO)、胶原、明胶、海藻酸钠、瓜尔胶中的一种或多种;水溶性高分子聚合物的浓度为0.01-0.2g/mL。
步骤(2)中,天然材料聚合物选自胶原、明胶、海藻酸钠、瓜尔胶中的一种或多种;天然材料聚合物的浓度为0.01-0.35g/mL。
步骤(3)中,PVP溶液的浓度为6-7mg/mL,PVP与FeCl3的反应质量比为30-35:10-12;单宁酸溶液的浓度为5-50mg/mL,FeCl3与单宁酸溶液的质量/体积比为100-120:1-10mg/mL。
步骤(3)中,透析为放置在10000Da透析袋中在水中透析3-4天,-45℃至-40℃冷冻干燥2-3天。
步骤(4)中,FeTAP纳米酶溶解于微针针尖溶液中的浓度为50-200ug/mL。
步骤(4)中,充分干燥是指干燥至固化,采用常温干燥或加热干燥,加热干燥的温度范围是30-50℃、时间范围是12-36h。
本发明还保护所述方法制备的光热抗菌微针。
与现有技术相比,本发明的有益效果是:
本发明的光热抗菌微针的制备方法将纳米酶封装在微针中,可以实现无痛、无创、高效的经皮给药。
本发明制备的光热抗菌微针具有pH值依赖性过氧化物酶模拟活性,可以在酸性条件下催化H2O2产生更多的·OH来杀死细菌。
本发明制备的光热抗菌微针具有出色的光热效率,可以进一步提高在NIR照射下的杀灭细菌的能力。
本发明制备的光热抗菌微针可以用于组织工程及再生医学等技术领域中。
附图说明
图1实施例1中得到的FeTAP的透射电镜图片。
图2实施例1中FeTAP纳米酶在不同环境下产生·OH的能力,图2中a是pH=5.5条件下产生·OH,b是pH=7.4条件下产生·OH。
图3实施例1中FeTAP纳米酶NIR照射下杀灭细菌效果更佳。
图4微针制备过程示意图;1-微针模具;2-天然材料聚合物溶液;3-水溶性高分子聚合物;4-微针。
图5实施例1中得到的微针的扫描电镜图片。
具体实施方式
以下通过实施例的形式对本发明的上述内容再作进一步的详细说明,但不应将此理解为本发明上述主题的范围仅限于以下的实施例,凡基于本发明上述内容所实现的技术均属于本发明的范围。
下述实施例中所使用的实验方法,如无特殊说明均为常规方法,所用的试剂、方法和设备,如无特殊说明均为本技术领域常规试剂、方法和设备。
实施例中,充分干燥是指干燥至固化,采用常温干燥或加热干燥,加热干燥的温度范围是30-50℃、时间范围是12-36h。
实施例1光热抗菌微针的制备,用于角膜炎治疗
(1)水溶性高分子聚合物溶液配制:
将1g的水溶性高分子聚合物瓜尔胶溶于100mL dH2O中,磁力搅拌得到瓜尔胶溶液。
(2)天然材料聚合物溶液配制步骤:
将3g的天然材料聚合物胶原溶于10mL dH2O中,磁力搅拌得到胶原溶液。
(3)FeTAP纳米酶制备步骤:
称取300mg的PVP加入到50mL dH2O,搅拌溶解,之后称取100mg的FeCl3加入到PVP溶液中,搅拌一段时间后加入10mL单宁酸溶液(浓度为10mg/mL),搅拌过夜。最后,将溶液在dH2O中透析3天,-42℃冷冻干燥2天,得到FeTAP纳米酶。透射电镜表明制备的FeTAP纳米酶具有均匀的形貌,如图1所示。相比于中性的环境,FeTAP纳米酶在酸性环境下可以产生更多的羟基自由基,如图2所示。此外,FeTAP纳米酶联合NIR照射比单纯的FeTAP显示出更好的杀菌效果,如图3所示。
(4)抗菌微针制备步骤:
将步骤(3)中制备的FeTAP纳米酶以60ug/mL的浓度溶解于步骤(2)中制备的胶原溶液中,并将得到的混合溶液加入到微针模板中,抽真空使得混合溶液完全浸入到微针模具中,充分干燥后将步骤(1)中制备的瓜尔胶溶液加入到所述微针模板的表面,再次充分干燥后,得到抗菌微针。微针的制备过程示意图及图片如图4和图5所示。
(5)大鼠角膜炎治疗
用手术刀将角膜上皮层刮除,并滴加金黄色葡萄球菌,制备角膜炎模型。在炎症部位插入抗菌微针,并用1mW/cm2 NIR照射2min,加入PBS的组作为对照组。所有手术都是在无菌环境下进行的。术后1,3,5,7天,用体式显微镜对炎症部位进行观察和拍照,并处死大鼠以获得炎症部位周围的组织进行进一步评估。
实施例2光热抗菌微针的制备,用于细菌感染创面治疗
(1)水溶性高分子聚合物溶液配制:
将10g的水溶性高分子聚合物PVA溶于100mL dH2O中,磁力搅拌得到PVA溶液。
(2)天然材料聚合物溶液配制步骤:
将2g的天然材料聚合物明胶溶于10mL dH2O中,磁力搅拌得到胶原溶液。
(3)FeTAP纳米酶制备步骤:
称取350mg的PVP加入到50mL dH2O,搅拌溶解,之后称取120mg的FeCl3加入到PVP溶液中,搅拌一段时间后加入2mL单宁酸溶液(浓度为45mg/mL),搅拌过夜。最后,将溶液在dH2O中透析3天,-42℃冷冻干燥2天,得到FeTAP纳米酶。透射电镜表明制备的FeTAP纳米酶具有均匀的形貌。
(4)抗菌微针制备步骤:
将步骤(3)中制备的FeTAP纳米酶以180ug/mL的浓度溶解于步骤(2)中制备的胶原溶液中,并将得到的混合溶液加入到微针模板中,抽真空使得混合溶液完全浸入到微针模具中,充分干燥后将步骤(1)中制备的瓜尔胶溶液加入到所述微针模板的表面,再次充分干燥后,得到抗菌微针。
(5)大鼠细菌感染创面治疗
用手术刀将大鼠表皮切掉,并滴加金黄色葡萄球菌,制备细菌感染创面模型。在炎症部位插入抗菌微针,并用0.75mW/cm2 NIR照射5min,加入PBS的组作为对照组。所有手术都是在无菌环境下进行的。术后1,3,5,7天,用体式显微镜对炎症部位进行观察和拍照,并处死大鼠以获得炎症部位周围的组织进行进一步评估。
以上所述,仅是本发明的较佳实施例,并非对本发明作任何形式上的限制,任何熟悉本专业的技术人员,在不脱离本发明技术方案范围内,依据本发明的技术实质,对以上实施例所作的任何简单的修改、等同替换与改进等,均仍属于本发明技术方案的保护范围之内。
Claims (8)
1.一种光热抗菌微针的制备方法,其特征在于,包括以下步骤:
(1)配制微针衬底溶液:采用水溶性高分子聚合物溶解得到微针衬底溶液,微针衬底溶液用于制备光热抗菌微针的衬底;
(2)配制微针针尖溶液:采用天然材料聚合物溶解得到微针针尖溶液,微针针尖溶液用于制备光热抗菌微针的针尖;
(3)制备FeTAP纳米酶:制备聚乙烯吡咯烷酮PVP溶液,向PVP溶液中加入FeCl3,搅拌后加入单宁酸TA溶液,继续搅拌后进行透析、冷冻干燥得到FeTAP纳米酶;
(4)制备光热抗菌微针:将步骤(3)制备的FeTAP纳米酶溶解于步骤(2)配制的微针针尖溶液中,加入到微针模板中,充分干燥;然后将步骤(1)中配制的微针衬底溶液加入到微针模板表面,再次充分干燥后,得到光热抗菌微针。
2.根据权利要求1所述的光热抗菌微针的制备方法,其特征在于:步骤(1)中,水溶性高分子聚合物选自聚乙烯醇(PVA)、聚氧化乙烯(PEO)、胶原、明胶、海藻酸钠、瓜尔胶中的一种或多种;水溶性高分子聚合物的浓度为0.01-0.2g/mL。
3.根据权利要求1所述的光热抗菌微针的制备方法,其特征在于:步骤(2)中,天然材料聚合物选自胶原、明胶、海藻酸钠、瓜尔胶中的一种或多种;天然材料聚合物的浓度为0.01-0.35g/mL。
4.根据权利要求1所述的光热抗菌微针的制备方法,其特征在于:步骤(3)中,PVP溶液的浓度为6-7mg/mL,PVP与FeCl3的反应质量比为30-35:10-12;单宁酸溶液的浓度为5-50mg/mL,FeCl3与单宁酸溶液的质量/体积比为100-120:1-10mg/mL。
5.根据权利要求1所述的光热抗菌微针的制备方法,其特征在于:步骤(3)中,透析为放置在10000Da透析袋中在水中透析3-4天,-45℃至-40℃冷冻干燥2-3天。
6.根据权利要求1所述的光热抗菌微针的制备方法,其特征在于:步骤(4)中,FeTAP纳米酶溶解于微针针尖溶液中的浓度为50-200ug/mL。
7.根据权利要求1所述的光热抗菌微针的制备方法,其特征在于:步骤(4)中,充分干燥是指干燥至固化,采用常温干燥或加热干燥,加热干燥的温度范围是30-50℃、时间范围是12-36h。
8.权利要求1-7任一项所述方法制备的光热抗菌微针。
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