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CN-122005424-A - Microneedle drug delivery system and preparation method and application thereof

CN122005424ACN 122005424 ACN122005424 ACN 122005424ACN-122005424-A

Abstract

The invention relates to the technical field of biological materials, and discloses a microneedle drug delivery system, a preparation method and application thereof. The microneedle drug delivery system comprises a needlepoint part and a back lining part, wherein the needlepoint part comprises a hydrogel matrix, the hydrogel matrix is prepared by physical crosslinking of 4-8% of hyaluronic acid and 0.5-10% of sodium carboxymethyl cellulose, and the back lining part is prepared from a polymer with wet adhesiveness. The invention solves the multiple challenges of insufficient mechanical strength, uncontrollable drug release, poor skin adhesion, complex process and the like of the microneedle in the prior art in a single system through ingenious material combination and structural design, and provides a solution of the microneedle drug delivery system with balanced performance, strong controllability and suitability for application.

Inventors

  • ZHU YANXIA

Assignees

  • 深圳瑞维塔生物科技有限公司

Dates

Publication Date
20260512
Application Date
20260226

Claims (10)

  1. 1. A microneedle delivery system comprising a needle tip portion and a backing portion; The needle point part comprises a hydrogel matrix, wherein the hydrogel matrix is prepared by physical crosslinking of 4-8% of hyaluronic acid and 0.5-10% of sodium carboxymethylcellulose; The raw material for preparing the backing portion includes a polymer having wet adhesion.
  2. 2. The microneedle delivery system of claim 1, wherein the hyaluronic acid forms a hydrogel matrix with sodium carboxymethyl cellulose by hydrogen bonding.
  3. 3. The microneedle delivery system of claim 1, wherein the hyaluronic acid has a molecular weight of 200-400 kDa and the sodium carboxymethylcellulose has a viscosity of 50-200 mPa-s.
  4. 4. The microneedle delivery system of claim 1, wherein the swelling ratio of hyaluronic acid to sodium carboxymethyl cellulose is 1000-1500%.
  5. 5. The microneedle delivery system of claim 1, wherein the wet-adhesive polymer comprises one of polyvinylpyrrolidone, sodium carboxymethyl cellulose, and a substance obtained by physically blending hyaluronic acid and sodium carboxymethyl cellulose.
  6. 6. The microneedle delivery system of claim 1, wherein the tip portion further comprises a first active substance loadable onto a hydrogel matrix, the first active substance comprising a small molecule chemical, a protein, a polypeptide, a nucleic acid, an antimicrobial agent, or the like.
  7. 7. The microneedle delivery system of claim 1, wherein the material of the backing portion further comprises a second active substance comprising one or more of nanosilver, zinc oxide nanoparticles, tea tree oil.
  8. 8. A method of preparing a microneedle delivery system according to any one of claims 1 to 7, comprising the steps of: Preparing a needle tip solution and a backing solution according to raw materials; the microneedle delivery system was prepared using a vacuum reverse mold process.
  9. 9. The method of preparing a hydrogel dressing according to claim 8, wherein the step of preparing the microneedle delivery system by vacuum reverse molding comprises: adding a needle point solution onto the microneedle mould, vacuumizing, and sucking off redundant needle point solution on the mould; And continuously adding a backing solution to the microneedle mould, and drying to obtain the microneedle drug delivery system.
  10. 10. Use of the microneedle delivery system of claims 1-7 for the manufacture of a medicament for delivery.

Description

Microneedle drug delivery system and preparation method and application thereof Technical Field The invention relates to the technical field of biological materials, in particular to a microneedle drug delivery system and a preparation method and application thereof. Background Transdermal administration is a non-invasive administration mode with the remarkable advantages of high patient compliance, avoidance of liver first pass effect, maintenance of stable blood concentration and the like. However, the stratum corneum, the outermost layer of human skin, constitutes a strong physical and chemical barrier, severely limiting the penetration of drug molecules, resulting in conventional transdermal patches being only suitable for small numbers of drugs with small molecular weight and high lipid solubility. Microneedle transdermal delivery technology is a revolutionary solution that has emerged in recent years. The technology can painless and minimally invasively pierce the stratum corneum of the skin through an array consisting of hundreds of micron-sized needle points to form a micron-sized drug delivery channel, so that the drug is directly delivered to the epidermis or dermis, and the limitations on the size, polarity and dosage form of the drug molecule are greatly overcome. Among the numerous types of microneedles, soluble microneedles prepared from biodegradable or water-soluble materials such as Hyaluronic Acid (HA), gelatin, polyvinyl alcohol (PVA) and the like have been the hot spot of research and major development in this field because of their excellent advantages of complete dissolution in interstitial fluid of skin, no generation of sharp medical wastes, high drug loading, and convenience for patients to use. Despite the remarkable progress of the prior art, the analysis of the prior literature and products shows that the prior hydrogel microneedle patch, particularly the soluble microneedle patch, still faces a series of technical bottlenecks and limitations which are urgently solved in the process of going to large-scale clinical application, namely, the mechanical strength and the skin penetration efficiency are difficult to be compatible. Soluble microneedles made from conventional polymeric materials such as HA often have insufficient mechanical strength to reliably penetrate human skin, especially in areas of thicker stratum corneum such as palms, soles, or in pathological thickening of skin caused by psoriasis, etc. The needle body is susceptible to bending, breaking or collapsing during penetration, resulting in failed administration. While there have been attempts to enhance mechanical properties by increasing the crosslink density, this often comes at the expense of rapid, complete solubility of the needle, which may lead to needle residues, initiate new biocompatibility problems, or affect complete drug release. Second, the controllability and intelligence level of the drug release behavior is insufficient. The drug release kinetics of the existing soluble microneedle mainly depends on the passive erosion speed of matrix materials, the release mode is single, the accurate control of programming and time sequence is difficult to realize, and the drug release on demand cannot be performed in response to specific pathological microenvironments (such as pH value, enzyme and active oxygen level change) of a focus part. For chronic disease management (e.g. diabetes, hypertension) requiring long-term administration or treatment scenarios requiring dose adjustment according to dynamic physiological signals (e.g. blood glucose fluctuations), there is a clear gap between control accuracy and intelligent feedback capability of the prior art. Although research has been explored to integrate environmentally-responsive hydrogels or microsensors in microneedles, the reliability of their structure, biosafety for long-term use, and complexity of mass production processes severely limit their clinical transformation prospects. Third, skin adhesion is contradictory to long-term dosing stability. The adhesive force of the back lining layer of the conventional microneedle patch to the skin is limited, the back lining layer is easy to loosen, shift and even fall off under the influence of daily activities of human bodies (such as sweating, skin stretching and clothes friction), the stable fit of the administration part in a plurality of hours to a plurality of days can not be ensured, and the accuracy of administration dosage and the treatment effect are directly influenced. Although the prior art enhances adhesion by introducing adhesive components such as polydopamine and acrylic pressure-sensitive adhesives, how to balance strong adhesion with mild peeling and avoid skin pain, injury or colloid residue when removing patches is still a key problem of deep optimization. This contradiction is particularly pronounced for patches that require administration for several days. Fourth, manufacturing proces