CN-116617150-B - Antifungal microneedle patch and preparation method and application thereof

CN116617150BCN 116617150 BCN116617150 BCN 116617150BCN-116617150-B

Abstract

The invention relates to an antifungal microneedle patch, a preparation method and application thereof, wherein the antifungal microneedle patch comprises a backing layer and a needle head arranged on the surface of the backing layer; the needle forms an n multiplied by n array on the surface of the back lining layer, the surface of the needle comprises a fatty acid coating containing antibacterial agent, the interior of the needle comprises a photosensitizer, and n is selected from integers. The antibacterial agent is lipophilic triazole antifungal agent. The fatty acid is selected from saturated fatty acids containing 6-12 carbon atoms. The invention innovatively combines the antifungal drug itraconazole and the photo-thermal agent/photosensitizer indocyanine green, and is loaded in the micro-needle, thereby being capable of carrying out painless minimally invasive local administration, realizing the effective killing of fungi by combining the antibacterial effect, the photo-thermal effect and the photodynamic effect of the antifungal drug released under the excitation of near infrared light, and avoiding irreversible damage to normal tissues.

Inventors

DING XIN
LIANG YIJING
YUAN PEIYAN

Assignees

中山大学·深圳

Dates

Publication Date: 20260508
Application Date: 20230427

Claims (7)

1. An antifungal microneedle patch, comprising a backing layer and a needle disposed on a surface of the backing layer; The needles form an n x n array on the surface of the backing layer; the needle surface comprises a lauric acid coating containing an antibacterial agent; The inside of the needle head comprises a photosensitizer; said n is selected from integers; The preparation method of the antifungal microneedle patch comprises the following steps: S1, adding chitosan solution into a mould, centrifuging, treating with alkali solution, drying, adding photosensitizer solution, centrifuging, drying, adding hyaluronate solution 1, centrifuging, adding hyaluronate solution 2, centrifuging, drying and shaping to obtain an intermediate product; s2, adding the lauric acid solution of the antibacterial agent into a blank mold, and centrifuging to obtain a mold containing the antibacterial agent solution; And S3, placing the intermediate product into a mold containing the antibacterial agent solution, and then drying and repeating for a plurality of times to obtain the antifungal microneedle patch.
2. The antifungal microneedle patch of claim 1, wherein the antimicrobial agent is a lipophilic triazole-based antifungal agent.
3. The antifungal microneedle patch of claim 2, wherein the antimicrobial agent is itraconazole.
4. The antifungal microneedle patch of claim 1, wherein the material of the needle comprises chitosan and the material of the backing layer is hyaluronate.
5. The antifungal microneedle patch of claim 1, wherein the photosensitizer is indocyanine green.
6. The antifungal microneedle patch of claim 1, wherein in step S1, the chitosan solution has a concentration of 3-5%, the photosensitizer solution has a concentration of 0.01-0.2%, the hyaluronate solution 1 has a concentration of 40-60%, and the hyaluronate solution 2 has a concentration of 10-30%.
7. The antifungal microneedle patch of claim 1, wherein the antimicrobial agent is present in an amount of 10-20% in the lauric acid solution of the antimicrobial agent in step S2.

Description

Antifungal microneedle patch and preparation method and application thereof Technical Field The invention belongs to the technical field of biological medicines, and particularly relates to an antifungal microneedle patch and a preparation method and application thereof. Background About 20-25% of people worldwide suffer from dermatophyte infections, which may develop into invasive fungal infections if not treated in time and thus threaten life health. At present, local preparations such as lotions, creams, gels and the like containing antifungal drugs are mostly used for treating dermatomycotic infection, but the local preparations are effective only on superficial dermatomycotic infection, and the local preparations have poor effect on deep infection caused by fungi capable of migrating to subcutaneous tissues through epidermis and dermis because the drugs are difficult to penetrate through horny layers. Treatment of deep fungal infections is usually carried out by oral antifungal therapy, but this systemic administration method causes major toxic side effects to the body due to lack of targeting. Thus, there is an urgent need to develop an effective, safe and easy-to-use method to combat skin infections. The microneedle is a patch consisting of an array of microneedles of 100-1000 μm in length, which is capable of penetrating the stratum corneum for administration, and is a minimally invasive topical administration without pain or with little pain because the penetration depth does not reach nerve endings in the dermis. Most microneedles are made of polymers for entrapment and controlled release of drugs. There have been studies on the use of microneedles for the detection and treatment of various diseases including skin cancer, skin infection, diabetes, eye diseases, etc. There have been several studies reported on microneedles for treating dermatophyte infections, such as microneedle patches manufactured using chitosan-polyethyleneimine copolymer as an antibacterial polymer, and encapsulating amphotericin to treat deep skin fungal infections. Also, the hyaluronic acid microneedle patch coated with itraconazole nanocrystals is used for treating skin candida albicans infection. However, in recent years, clinically discovered multi-drug resistant fungi are increasingly growing, and the multi-drug resistant fungi are difficult to kill only by antibiotics antifungal drugs. Photothermal treatment refers to that a photothermal agent generates temperature rise under the excitation of light, so that a fungus structure is physically destroyed, and a sterilization effect is achieved. This physical disruption mechanism does not allow the fungus to develop resistance. However, the use of photothermal sterilization alone generally requires high temperatures and long times, which inevitably cause damage to surrounding normal cells and tissues. Photodynamic therapy is a treatment method that causes inactivation of fungi by activating photosensitizers with light to generate cytotoxic reactive oxygen species, which cause oxidative damage to cellular components (lipids, proteins and nucleic acids). Photodynamic therapy exhibits broad-spectrum antimicrobial properties and avoids fungal resistance. However, the low penetration efficiency of free photosensitizers into the skin, poor water solubility, instability, etc. have limited the further clinical application of photodynamic therapy. Therefore, a new technical solution is needed to solve the problems existing in the prior art. Disclosure of Invention In order to solve the defects in the prior art, the invention creatively combines the antifungal drug itraconazole and the photothermal agent/photosensitizer indocyanine green, and is loaded in the micro needle for painless minimally invasive local administration, and the antibacterial effect, the photothermal effect and the photodynamic effect of the antifungal drug released under the excitation of near infrared light are combined to realize the effective killing of fungi without irreversible damage to normal tissues. It is an object of the present invention to provide an antifungal microneedle patch comprising a backing layer and a needle disposed on a surface of the backing layer; The needles form an n x n array on the surface of the backing layer; the needle surface comprises a fatty acid coating containing an antimicrobial agent; The inside of the needle head comprises a photosensitizer; the n is selected from integers. Further, the antibacterial agent is a lipophilic triazole antifungal agent. Further, the antibacterial agent is itraconazole. Further, the fatty acid is selected from saturated fatty acids having 6 to 12 carbon atoms. Further, the fatty acid is preferably lauric acid. Further, the material of the needle is chitosan, and the material of the back lining layer is hyaluronate. Further, the photosensitizer is indocyanine green. Itraconazole (ITZ, CAS accession number 84625-61-6) is a lipophilic triazole anti