CN-122005427-A - Application of abdominal cavity implantable hydrogel microneedle in colorectal cancer abdominal wall infiltration focus

CN122005427ACN 122005427 ACN122005427 ACN 122005427ACN-122005427-A

Abstract

The invention discloses an application of a hydrogel microneedle capable of being implanted into an abdominal cavity in colorectal cancer abdominal wall infiltration focus, relating to the field of medicine; the method is applied to clinical treatment of rectal cancer abdominal wall infiltration focus, and comprises the following steps of opening abdominal exploration of a mouse to determine the position of the abdominal wall infiltration focus after full anesthesia of the mouse; step two, clamping and delivering the sterilized microneedle sheet into the abdominal cavity by using a noninvasive clamp, step three, attaching a microneedle substrate to the surface of a focus under direct vision, pressing to enable a needle body to penetrate the peritoneal membrane, step four, flushing with normal saline to confirm that the microneedle is fixed, withdrawing an instrument, and suturing an incision. The microneedle physically penetrates through the surface layer of the peritoneum, directly delivers the medicine to the deep layer of the infiltrating focus, overcomes the inefficiency problem caused by the peritoneal barrier in the traditional therapy, and gradually swells and degrades GelMA/hyaluronic acid hydrogel in body fluid, so that collagenase, macrophage scavenger and anti-tumor medicine are continuously released, and the local effective concentration can be maintained for more than two weeks.

Inventors

CAO GUODONG
Cao Huake
CHEN BO
JIANG ZILONG
FU RUI

Assignees

安徽医科大学第一附属医院

Dates

Publication Date: 20260512
Application Date: 20260316

Claims (3)

1. The application of the abdominal cavity implantable hydrogel microneedle in colorectal cancer abdominal wall infiltration focus is characterized in that the application is applied to clinical treatment of colorectal cancer abdominal wall infiltration focus, and the specific application method comprises the following steps: opening the abdomen of the mice to explore and determine the position of the focus of infiltration of the abdominal wall after the mice are full-anesthetized; Step two, clamping the sterilized microneedle sheet by using a noninvasive clamp and sending the sterilized microneedle sheet into the abdominal cavity; Attaching the microneedle substrate to the surface of a focus under direct vision, and pressing to enable the needle body to penetrate the peritoneum; And fourthly, flushing with normal saline to confirm fixation of the micro needle, withdrawing the instrument, and suturing the incision.
2. The use of the intraperitoneally implantable hydrogel microneedle according to claim 1, wherein the intraperitoneally implantable hydrogel microneedle consists of GelMA10% -20%, hyaluronic acid 3% -8%, collagenase, macrophage scavenger and antitumor drug 0.1% -5% and photoinitiator.
3. Use of the laparoscopically implantable hydrogel microneedle according to claim 1 for treating a lesion infiltrated by the abdominal wall of colorectal cancer, wherein the method for preparing the laparoscopically implantable hydrogel microneedle comprises the steps of: a1, preparing a solution: Dissolving GelMA and hyaluronic acid in PBS at 37 ℃ and magnetically stirring for 2 hours until the GelMA and hyaluronic acid are completely dissolved; Oxaliplatin, collagenase and macrophage scavenger are added, and stirred for 30 minutes in a dark place, so as to ensure the uniform dispersion of the medicine; Adding LAP initiator, and mixing for 10 minutes in dark place; a2, mould forming: Injecting the mixed solution into a Polydimethylsiloxane (PDMS) microneedle mould; Centrifuging to discharge bubbles to fill the needle tip with the solution; a3, photo-crosslinking and curing: Irradiating ultraviolet light for 60 seconds to form a solid microneedle array; and A4, demolding and sterilizing: peeling off the PDMS mould to obtain a hydrogel microneedle sheet; sterilizing for 24 hours, drying at low temperature, and preserving with isolated oxygen.

Description

Application of abdominal cavity implantable hydrogel microneedle in colorectal cancer abdominal wall infiltration focus Technical Field The invention relates to the field of medicine, in particular to application of a hydrogel microneedle capable of being implanted into an abdominal cavity in colorectal cancer abdominal wall infiltration focus. Background Colorectal cancer abdominal wall infiltration and peritoneal metastasis are common complications of advanced patients, and current clinic mainly depends on systemic intravenous chemotherapy or intraperitoneal hot-infusion chemotherapy (HIPEC). Wherein: Intravenous chemotherapy acts on lesions through blood circulation, but due to the presence of the peritoneal-plasma barrier, the efficiency of drug penetration into peritoneal tissue is significantly limited; Although the peritoneal perfusion chemotherapy can improve the exposure of local medicaments, the fluid medicaments are easy to be quickly removed by the peritoneal metabolism, and the effective concentration is difficult to maintain at the focus part; Topical sustained release implants (e.g., fibrin glue delivery) can extend the duration of drug action, but they cannot penetrate tough peritoneal tissue barriers and the drug is difficult to reach deep invasive lesions. For this reason, the invention proposes the application of the laparoscopically implantable hydrogel microneedle in colorectal cancer abdominal wall infiltration focus. Disclosure of Invention The invention aims to solve the defects in the prior art, and provides an application of an abdominal cavity implantable hydrogel microneedle in colorectal cancer abdominal wall infiltration focus. In order to achieve the above purpose, the present invention adopts the following technical scheme: The application of the abdominal cavity implantable hydrogel microneedle in colorectal cancer abdominal wall infiltration focus is applied to clinical treatment of colorectal cancer abdominal wall infiltration focus, and the specific application method comprises the following steps: opening the abdomen of the mice to explore and determine the position of the focus of infiltration of the abdominal wall after the mice are full-anesthetized; Step two, clamping the sterilized microneedle sheet by using a noninvasive clamp and sending the sterilized microneedle sheet into the abdominal cavity; Attaching the microneedle substrate to the surface of a focus under direct vision, and pressing to enable the needle body to penetrate the peritoneum; And fourthly, flushing with normal saline to confirm fixation of the micro needle, withdrawing the instrument, and suturing the incision. The hydrogel microneedle capable of being implanted into the abdominal cavity consists of 10% -20% of GelMA, 3% -8% of hyaluronic acid, collagenase, macrophage scavenger and 0.1% -5% of antineoplastic drug and photoinitiator. Preferably, the preparation method of the abdominal cavity implantable hydrogel microneedle comprises the following steps: a1, preparing a solution: Dissolving GelMA and hyaluronic acid in PBS at 37 ℃ and magnetically stirring for 2 hours until the GelMA and hyaluronic acid are completely dissolved; Oxaliplatin, collagenase and macrophage scavenger are added, and stirred for 30 minutes in a dark place, so as to ensure the uniform dispersion of the medicine; Adding LAP initiator, and mixing for 10 minutes in dark place; a2, mould forming: Injecting the mixed solution into a Polydimethylsiloxane (PDMS) microneedle mould; Centrifuging to discharge bubbles to fill the needle tip with the solution; a3, photo-crosslinking and curing: Irradiating ultraviolet light for 60 seconds to form a solid microneedle array; and A4, demolding and sterilizing: peeling off the PDMS mould to obtain a hydrogel microneedle sheet; sterilizing for 24 hours, drying at low temperature, and preserving with isolated oxygen. The beneficial effects of the invention are as follows: 1. The microneedle provided by the invention physically penetrates through the surface layer of the peritoneum, directly delivers the drug to the deep layer of the infiltrated focus, overcomes the inefficiency problem caused by the peritoneal barrier in the traditional therapy, gradually swells and degrades the GelMA/hyaluronic acid hydrogel in body fluid, continuously releases collagenase, macrophage scavenger and anti-tumor drug, maintains the local effective concentration for more than two weeks, and simultaneously, the implantation position of the microneedle is tightly attached to the focus, thereby reducing the systemic diffusion of the drug, remarkably reducing the systemic side effects such as bone marrow suppression, neurotoxicity and the like, and the microneedle substrate can be biodegraded to avoid secondary taking out wounds. Drawings FIG. 1 is a flow chart of an application method of an abdominal cavity implantable hydrogel microneedle in colorectal cancer abdominal wall infiltration focus; FIG. 2 is a cytoc