CN-122005420-A - Long-acting administration frozen soluble microneedle, preparation method and application thereof

Abstract

The invention relates to a long-acting drug administration frozen soluble microneedle, a preparation method and application thereof, the method is to solidify and shape the water-containing temperature sensitive gel precursor system under the low temperature condition to obtain the solid micro needle which has enough mechanical strength and can penetrate into the skin surface layer. The micro needle can be quickly converted into gel state from solid state after contacting with body temperature, and a local gel matrix is formed under the skin, so as to realize in-situ retention and slow release of the carried medicine. The technology improves the formability and the penetrating power of the micro needle by freezing and solidifying, and constructs a subcutaneous drug reservoir by utilizing the phase transition characteristic of the temperature-sensitive gel, thereby improving the sustainability and the targeting of local administration. The method has simple process and can be used for the development of the microneedle preparation in the fields of skin and local treatment.

Inventors

• YU ZIYI
• GU JIAWEI
• ZHANG JING
• ZHENG HAIPING

Assignees

• 南京工业大学

Dates

Publication Date

20260512

Application Date

20260112

Claims (9)

1. 1. A method for preparing a long-acting administration frozen soluble microneedle, which is characterized by comprising the following steps: (1) The construction of the drug-carrying microneedle matrix comprises the steps of mixing microencapsulated active ingredients with a temperature-sensitive polymer matrix to obtain a uniform drug-carrying microneedle matrix; (2) And (3) freeze molding, namely injecting the drug-loaded microneedle matrix obtained in the step (1) into a microneedle mould, and performing freeze curing under a low-temperature condition to form a solid microneedle structure by the drug-loaded microneedle matrix.
2. 2. The method of claim 1, wherein the microencapsulated active ingredient is selected from one or more of cells, bacteria, liposomes, exosomes, collagen that are available for delivery.
3. 3. The method according to claim 1, wherein the temperature sensitive polymer matrix is selected from one or more of polyoxyethylene-polyoxypropylene-polyoxyethylene triblock copolymers (F127, F68), PLGA-PEG-PLGA triblock copolymers and methacryloylated gelatin (GelMA).
4. 4. The method of claim 1, wherein the microneedle mould is made of one or more of Polydimethylsiloxane (PDMS), silicone rubber, polytetrafluoroethylene, or a metallic material.
5. 5. The method of claim 1, wherein the solid state microneedle structure has a height of 500 μιη to 800 μιη.
6. 6. The method of claim 1, wherein the temperature sensitive polymer matrix has a phase transition temperature of 0 ℃ to 40 ℃.
7. 7. A long-acting freeze-soluble microneedle prepared according to the method of any one of claims 1 to 6.
8. 8. Use of a long-acting drug delivery cryosoluble microneedle according to claim 7 in the field of topical drug delivery.
9. 9. The use according to claim 8, characterized in that said field of topical administration comprises in particular the treatment of alopecia, the treatment of scalp inflammation, the topical chemotherapy of cutaneous tumours and the introduction of dermatological active ingredients.

Description

Long-acting administration frozen soluble microneedle, preparation method and application thereof Technical Field The invention relates to the technical field of biological medicine delivery, in particular to a long-acting drug-delivery frozen soluble microneedle and a preparation method thereof, which are particularly suitable for the scenes of local skin treatment, beauty repair and the like and can realize long-acting and accurate release of microencapsulated active ingredients. Background Frozen microneedles (also known as ice microneedles) are a type of transdermal drug delivery vehicle developed in recent years. Unlike other types of microneedles, such microneedles release drugs, proteins or cells by freezing a drug-containing liquid or biological agent into a solid needle body at low temperature, and directly withdrawing the needle body from the frozen environment to penetrate the skin when in use, and gradually thawing the needle body by body temperature. The frozen microneedle has the advantages of noninvasive property, controllability, thermosensitive active substance loading and the like, and is widely applied to the fields of drug delivery, vaccine immunization, skin repair, tissue regeneration and the like. Compared with the traditional external preparation, the preparation can maintain the stability of the medicine or the bioactive substances for a long time at low temperature and realize high-efficiency transdermal delivery through the micro-channel. However, existing frozen microneedle systems generally suffer from the limitation of "melt immediate release". The needle body is mostly made of water or a conventional low-temperature medium as a matrix, and is quickly melted into a liquid state under the action of body temperature after penetrating into the skin, so that the medicine is easy to diffuse and run away along with the liquid body, and a stable medicine reservoir is difficult to form in tissues, so that the duration of the medicine effect is limited. In addition, the prior art focuses on the administration of an epidermis layer, and lacks a structural design capable of in-situ gelation at body temperature and realizing slow release medicine storage. For example, chinese patent application CN111329832a discloses a nano-lipid carrier microneedle for treating alopecia, which improves hair follicle targeting and local retention by encapsulating finasteride nano-lipid carrier at the tip of the needle, but the system belongs to a soluble microneedle which is immediately dissolved and released after being inserted into the skin, and fails to form a durable drug depot structure. PCT international patent application WO2022127662A1 discloses a frozen microneedle based on a hydrogel material, which can rapidly release a drug or cells by freeze-molding and body temperature thawing, and can keep active substances stable, but does not use the thermal response characteristics of the material to form a gel structure, and the drug solution is easy to diffuse and lose after thawing. The US20220354998A1 uses a preformed gel filling method, and the freezing is only used for shaping, and the phase change does not occur during use. In conclusion, the existing frozen microneedle system focuses on rapid release, generally lacks the capability of forming gel in situ and forming a slow-release drug depot under the action of body temperature, and is difficult to realize long-term retention and controlled release of drugs. Disclosure of Invention In order to solve the problems, one of the purposes of the present invention is to provide a long-acting drug delivery frozen soluble microneedle and a preparation method thereof, which realize high-efficiency load, stable storage and long-acting transdermal release of microencapsulated active ingredients, and simultaneously have good biocompatibility and formability. As one aspect of the present invention, there is provided a method for preparing a long-acting administration freeze-soluble microneedle, comprising the steps of: And 1, constructing a medicine-carrying microneedle matrix, namely mixing the microencapsulated active ingredients with a temperature-sensitive polymer matrix, and fully mixing the mixture by stirring, ultrasonic and other modes to ensure that a mixed system is uniform and obtain uniform medicine-carrying microneedle temperature-sensitive gel. Wherein the temperature-sensitive polymer matrix is selected from one or more of polyoxyethylene-polyoxypropylene-polyoxyethylene triblock copolymer (F127, F68), PLGA-PEG-PLGA triblock copolymer and methacrylic acid gelatin (GelMA) system, and the microencapsulated active ingredient is selected from one or more of liposome, exosome, small molecule drug, growth factor, protein and polypeptide with therapeutic or cosmetic effect on skin. And 2, freeze molding, namely injecting the medicine-carrying microneedle matrix in the step 1 into a microneedle mould to ensure that the medicine-carrying microneedle matr