生物相容透皮给药微针治疗浅表肿瘤
作者:
作者单位:

1.广东医科大学药学院,东莞 523808;2)中国科学院深圳先进技术研究院,中国科学院健康信息学重点实验室,广东省纳米医药重点实验室,深圳 518055;3)深圳市第三人民医院(南方科技大学第二附属医院),国家感染性疾病临床医学研究中心,肝病研究所,深圳 518112

作者简介:

尹婷 Tel:0755-86392210,E-mail:wsyt132@163.comYIN Ting. Tel: 86-755-86392210,E-mail: wsyt132@123.com

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中图分类号:

基金项目:

国家自然科学基金(81901864), 深圳市科技计划项目 (JCYJ20210324115611032),广东省自然科学基金(2022A1515011 337),广东省普通高校重点领域专项(2022ZDZX2022),广东省 大学生科技创新专项资金(pdjh2022b0227),2022年广东医科大学 博士研究经费,广东省高校特色创新项目(2021KTSCX036) 和广 东省中医局中药研究项目(20221206) 资助。


Biocompatible Transdermal Microneedles for Superficial Tumor Therapy
Author:
Affiliation:

1)School of Pharmacy, Guangdong Medical University, Dongguan 523808, China;2)CAS Key of Laboratory of Health Informatics, Guangdong Key Laboratory of Nanomedicine, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China;3)Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital, Shenzhen 518112, China

Fund Project:

This work was supported by grants from The National Natural Science Foundation of China (81901864), Shenzhen Science and Technology Program (JCYJ20210324115611032), Natural Science Foundation of Guangdong Province (2022A1515011337), Guangdong Provincial University Key Field Project (2022ZDZX2022), Guangdong Province University Students Science and Technology Innovation Special Fund (pdjh2022b0227), Funds for PHD researchers of Guangdong Medical University, Characteristic Innovation Project of Universities in Guangdong Province (2021KTSCX036), and Traditional Chinese Medicine Research Project of Guangdong Traditional Chinese Medicine Bureau (20221206).

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    摘要:

    复杂的肿瘤微环境导致抗肿瘤药物在肿瘤组织内递送效率低下,严重阻碍了药物对浅表肿瘤的治疗效果。生物相容透皮给药微针凭借较高的机械强度,刺穿皮肤角质层,将微针内的药物递送至浅表肿瘤组织内,提高生物利用度,改善静脉注射、口服给药的肝肾毒性等问题。本文介绍了生物相容透皮给药微针的设计及其在癌症化疗、光动力治疗、光热治疗、免疫治疗、基因治疗等领域的研究进展,对浅表肿瘤的微创、局部递药和精准、高效治疗具有重要指导意义。

    Abstract:

    The complex tumor microenvironment leads to the inefficient intra-tumor delivery of antitumor drugs severely restrict the therapeutic effect of drugs on superficial tumors. At present, the main treatment methods for superficial tumors are surgical resection, chemotherapy, radiotherapy. These therapies can destroy tumor tissue or inhibit the growth of cancer cells in the short term, but the long-term treatment results are not satisfactory. With the research of anti-tumor treatment, chemotherapy , photodynamic therapy (PDT), photothermal therapy (PTT), gene therapy and immunotherapy and other new combined treatment strategies have the advantages of good therapeutic effect, small invasion, and low toxic and side effects, and have shown great potential for the treatment of superficial tumors. In order to achieve good therapeutic efficacy, it is necessary to effectively deliver therapeutic drugs (photosensitizers, photothermal agents, chemotherapeutic drugs, etc.) to the tumor site to exert anti-tumor effect. Based on the major drawbacks of the traditional administration strategy, such as low bioavailability of oral administration, pain, poor targeting, and systemic toxicity caused by subcutaneous/intravenous administration. It is important to develop safe and effective anticancer drug delivery strategies to promote novel cancer therapies. The transdermal delivery system (TDS) can deliver the drug through the stratum corneum of skin into the dermis and through capillaries into the bloodstream, effectively overcoming low bioavailability associated with oral administration. In addition, subcutaneous/intravenous administration often causes pain sensation defects, TDS can significantly improving patient medication compliance. However, due to the presence of a cuticle barrier on the skin that hinders drug penetration, there is a significant reduction in drug delivery efficiency, limiting its further application. The emergence of biocompatible transdermal microneedles presents a promising solution for enhancing drug penetration in TDS. These microneedles are composed of biodegradable components, such as polymers and polysaccharides, serving as matrix materials that encapsulate drugs. This innovative approach represents a minimally invasive local drug delivery system with the dual functionality of subcutaneous injection and transdermal drug administration. The biocompatible transdermal microneedles with high rigidity can effectively puncture the skin cuticle and deliver agents within the microneedle to superficial tumor tissues via controlled drug release, which would significantly improve drug bioavailability and avoid toxicity to livers/kidneys compared with conventional drug intravenous/oral administration. The biodegradable polymer material of microneedles avoids the safety risks and reduces the risk of cross infection, which is caused by the metal materials of solid microneedles or non-degradable polymers. In addition, biocompatible transdermal microneedles can overcome the shortcomings of low-dose hollow coated microneedles by encapsulating the drug into the entire tip for efficient drug loading. Meanwhile, the height and volume of the needle tip can be adjusted by changing the mold structure in order to meet the needs of different depth and dosage of the drug. Here, the design of biocompatible transdermal microneedles for cancer chemotherapy, PDT and PTT, immunotherapy, adoptive cell therapy and gene therapy in introduced. We also summarize the challenges of biocompatible transdermal microneedles-mediated superficial tumor therapy, to help promote potential translational superficial tumor applications of microneedles.

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石清霞,尹婷,郑明彬,蔡林涛.生物相容透皮给药微针治疗浅表肿瘤[J].生物化学与生物物理进展,2023,50(11):2636-2648

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历史
  • 收稿日期:2022-11-06
  • 最后修改日期:2023-10-13
  • 接受日期:2023-01-09
  • 在线发布日期: 2023-11-22
  • 出版日期: 2023-11-20