生物相容透皮给药微针治疗浅表肿瘤

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。

Biocompatible Transdermal Microneedles for Superficial Tumor Therapy

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.