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CN-121987553-A - 3D printing composite hydrogel microneedle and preparation method and application thereof

CN121987553ACN 121987553 ACN121987553 ACN 121987553ACN-121987553-A

Abstract

The invention relates to a 3D printing composite hydrogel microneedle, which comprises methacryloylated chitosan, o-nitrobenzyl alcohol polyethylene glycol, resveratrol and liposome, wherein the resveratrol is coated on the liposome. The preparation method comprises the steps of preparing resveratrol-loaded liposome and preparing the 3D printing composite hydrogel microneedle, and provides an innovative microneedle patch with long-acting administration, excellent biocompatibility and myocardial repair function through the organic combination of pharmacological activity of resveratrol, a PEGNB controllable skeleton, adhesion and antibacterial properties of CSMA, accurate drug delivery capability of the microneedle and precise preparation advantages of 3D printing, and provides a new solution for myocardial injury treatment.

Inventors

  • FENG LONGBAO
  • Huang Shanghui

Assignees

  • 广州贝奥吉因生物科技股份有限公司

Dates

Publication Date
20260508
Application Date
20260130

Claims (10)

  1. 1. The 3D printing composite hydrogel microneedle is characterized by comprising methacryloylated chitosan, o-nitrobenzyl alcohol polyethylene glycol, resveratrol and liposome, wherein the resveratrol is coated on the liposome.
  2. 2. The 3D printing composite hydrogel microneedle according to claim 1, wherein the mass concentration of the methacryloylated chitosan, the o-nitrobenzyl alcohol polyethylene glycol, the resveratrol and the liposome in the 3D printing composite hydrogel microneedle is 10-20 mg/mL, 50-90 mg/mL, 0.5-1 mg/mL and 1-2 mg/mL, respectively.
  3. 3. The method for preparing the 3D printing composite hydrogel microneedle according to any one of claims 1 to 2, comprising the following steps: the resveratrol loaded liposome is prepared by dissolving hydrogenated soybean lecithin, cholesterol and resveratrol, performing ultrasonic treatment, dripping into water, and evaporating; The preparation method of the 3D printing composite hydrogel microneedle comprises the steps of taking a resveratrol loaded liposome solution, adding a photoinitiator and lemon yellow, uniformly mixing, adding methacryloyl chitosan and o-nitrobenzyl alcohol polyethylene glycol, printing and washing to obtain the 3D printing composite hydrogel microneedle.
  4. 4. A method of preparing the methacryloylated chitosan according to claim 3, comprising the steps of: Dissolving chitosan in acetic acid solution, diluting with ethanol, performing ultrasound, adding methacrylic anhydride, stirring at room temperature, dialyzing, and freeze-drying to obtain the chitosan-containing gel, wherein the stirring time is 6-8 hours; according to the mass ratio, the chitosan and the methacrylic anhydride are 1 (1-2).
  5. 5. A method according to claim 3, wherein the preparation of resveratrol loaded liposomes comprises the steps of: Dissolving hydrogenated soybean lecithin, cholesterol and resveratrol in absolute ethanol, performing ultrasonic treatment, dripping into water, and evaporating to obtain the final product; according to the mass ratio, the hydrogenated soybean lecithin is 1 (2-3) of the cholesterol and 1-2 of the resveratrol.
  6. 6. The method of preparing according to claim 3, wherein the preparation of the 3D printed composite hydrogel microneedle comprises the steps of: Taking a resveratrol loaded liposome solution, adding a photoinitiator and lemon yellow, uniformly mixing by vortex, adding methacryloyl chitosan and o-nitrobenzyl alcohol polyethylene glycol for dissolution, printing and washing to obtain the 3D printing composite hydrogel microneedle; The photoinitiator comprises LAP, and the weight ratio of the resveratrol loaded liposome solution to the photoinitiator is (1-2) mL (1-2) mg (0.5-1.2) mg.
  7. 7. The method according to claim 6, wherein the printing parameters are set to 10mW/cm 2 for light intensity, 20s for exposure time, 1 for the number of layers of the substrate, and 25s for exposure time of the substrate.
  8. 8. The preparation method of claim 3, wherein in the 3D printing composite hydrogel microneedle, the mass concentration of the methacryloylated chitosan, the o-nitrobenzyl alcohol polyethylene glycol, the resveratrol and the liposome is respectively 10-20 mg/mL, 50-90 mg/mL, 0.5-1 mg/mL and 1-2 mg/mL.
  9. 9. Use of a 3D printed composite hydrogel microneedle according to claims 1-2, or a 3D printed composite hydrogel microneedle obtained by the method of preparation according to claims 3-8, for the preparation of a product for myocardial repair.
  10. 10. A product for myocardial repair comprising the 3D printed composite hydrogel microneedle according to claims 1-2 or the 3D printed composite hydrogel microneedle obtained by the method of preparation according to claims 3-8.

Description

3D printing composite hydrogel microneedle and preparation method and application thereof Technical Field The invention relates to the technical field of hydrogel microneedles, in particular to a 3D printing composite hydrogel microneedle, and a preparation method and application thereof. Background Myocardial injury is followed by inflammatory response, oxidative stress and apoptosis, ultimately leading to an irreversible decline in cardiac function. In recent years, various strategies based on biological materials have been tried in order to improve the microenvironment of the damaged area and promote the restoration of cardiac function. For example, a hydrogel stent constructed by natural or synthetic polymers can form a protective barrier on the surface of heart and realize local drug release by incorporating active molecules, a liposome drug delivery system based on nanotechnology can encapsulate antioxidants or signal molecules to improve the stability and sustained release performance of the drug to a certain extent, and in addition, the cardiac patch can be used as an exogenous supporting means to improve the mechanical support and drug enrichment of myocardial injury areas in a macroscopic level. In recent years, the microneedle technology is gradually applied to myocardial repair research, and by virtue of an array structure of the microneedle technology, a surface barrier can be broken through, medicines can be accurately delivered to the surface of damaged myocardium, and the local medicine utilization rate is effectively improved. Meanwhile, the rise of 3D printing technology provides a highly controllable forming method for preparing the micro-needle and the heart patch, so that the height, density and arrangement mode of the needle can be individually designed according to the specific condition of myocardial injury. In summary, existing research has evolved from single drug delivery to multi-functional composite systems, attempting to achieve precise intervention on myocardial injury through materials engineering and manufacturing techniques. Despite the advances made in myocardial injury repair by current research, significant shortcomings remain. Firstly, most of the traditional hydrogel patches are based on natural polymers (such as hyaluronic acid, gelatin and the like), and have good biocompatibility, but the mechanical strength and toughness are insufficient, high-frequency dynamic stress caused by continuous heart contraction is difficult to bear, and the traditional hydrogel patches are easy to fall off or deform, so that the treatment effect is reduced. In addition, the degradation rate of such hydrogels is not controllable and often is difficult to match with the myocardial repair process. Secondly, although the liposome is widely applied to drug delivery, the liposome has limited stability under a dynamic heart environment, is extremely easy to diffuse along with blood flow to cause insufficient drug localization, is difficult to form continuous and effective drug concentration in a damaged area, and has limited therapeutic effect due to lack of immobilization when the liposome is singly used. Again, although the existing microneedle patch has potential in the aspect of local drug delivery, most of materials are single hydrogel, the mechanical strength of a needle body is insufficient, stable penetration of a myocardial fibrous layer is difficult to realize, the microneedle patch is easy to break or deform under the action of tissue stress, structural parameters such as the height, the density and the like of the microneedle are mostly dependent on mold molding, the controllability is lacking, and the personalized requirements of different patient injury areas are difficult to meet. Finally, although 3D printing technology has been applied in tissue engineering, its combination with heart repair materials is still in an exploring stage, most of existing 3D printed heart patches are mainly single-function, lack of collaborative design of drug delivery and tissue repair, and fail to simultaneously satisfy key requirements of mechanical matching, accurate positioning, drug release, long-term stability and the like. Therefore, the prior art only solves a certain aspect of the myocardial repair process, lacks systemicity and integrity, and is difficult to realize efficient, long-term and personalized myocardial injury treatment. Disclosure of Invention Aiming at the defects of the prior art, the invention provides a 3D printing composite hydrogel microneedle, which comprises methacryloyl Chitosan (CSMA), o-nitrobenzyl alcohol polyethylene glycol (PEGNB), resveratrol and liposome (Lip), wherein the resveratrol is coated on the liposome. In one embodiment, in the 3D printing composite hydrogel microneedle, the mass concentration of the methacryloylated chitosan, the o-nitrobenzyl alcohol polyethylene glycol, the resveratrol and the liposome is respectively 10-20 mg/mL, 50-90 mg/mL, 0.5-1