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Microneedle patch for enhancing accumulation of protoporphyrin IX in solid tumor and preparation method of microneedle patch

A technology for microneedle sticking and solid tumors, which can be applied to preparations for in vivo experiments, medical preparations containing active ingredients, antineoplastic drugs, etc. It can solve the problems of low PpIX synthesis concentration, tumor hypoxia, and low treatment efficiency of solid tumors and other issues to achieve the effect of increasing the accumulation of PpIX

Active Publication Date: 2022-08-09
SHENZHEN UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] In view of the above deficiencies in the prior art, the purpose of the present invention is to provide a microneedle patch that enhances the accumulation of PpIX in solid tumors and its preparation method, aiming to solve the problem of lack of specific delivery strategy in the existing 5-ALA-PDT. The resulting tumor hypoxia, low concentration of PpIX synthesis, low efficiency of solid tumor treatment, etc.

Method used

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  • Microneedle patch for enhancing accumulation of protoporphyrin IX in solid tumor and preparation method of microneedle patch
  • Microneedle patch for enhancing accumulation of protoporphyrin IX in solid tumor and preparation method of microneedle patch
  • Microneedle patch for enhancing accumulation of protoporphyrin IX in solid tumor and preparation method of microneedle patch

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Embodiment 1

[0093] Example 1: Preparation of a Microneedle Patch for Enhanced PpIX Accumulation in Solid Tumors

[0094] Dissolve 100 mg of HSA in 10 mL of Dulbecco's medium without dextrose, then add 100 μL of CuCl 2 solution (0.1M concentration, deionized water solvent). The system was sealed and mineralized at 37°C for 24 hours. Subsequently, 100 μL of CaCl was 2 The solution (1 M concentration, deionized water solvent) was added to the system and mineralization was continued at 37°C for 24 hours. After that, CCP NPs were isolated by centrifugation (12000 rpm, 10 minutes).

[0095] Disperse 2 mg of CCP NPs in 2 mL of 0.1 mM phosphate buffered saline (PBS, pH adjusted to 7.4) to obtain a CCP NPs solution. Dissolve 2 mg of EDC·HCl in 100 μL of DMSO directly and add it to the above CCP NPs solution. After stirring and activation for 1 hour at room temperature and in the dark, 2 mg of N-hydroxysuccinimide (NHS) was dissolved in 100 μL of DMSO, and then added to the reaction solution af...

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Abstract

The invention discloses a microneedle patch for enhancing accumulation of protoporphyrin IX in a solid tumor and a preparation method of the microneedle patch. The method comprises the following steps: dissolving albumin into a Duncheng culture medium, taking the albumin as a template, and adding CuCl2 and CaCl2 for mineralization to obtain CCP nanoparticles; cAT and 5-ALA are loaded to the surfaces of the CCP nano-particles through a one-step carbodiimide coupling method and an electrostatic adsorption method respectively, and CCPCA nano-particles are obtained; and loading the CCPCA nanoparticles and the microneedle matrix solution into a microneedle mold, and performing vacuum drying and demolding to obtain the microneedle patch for enhancing PpIX accumulation in the solid tumor. According to the microneedle patch, the PpIX and O2 level in a tumor can be increased through precise delivery of CAT and 5-ALA, meanwhile, guidance of real-time bimodal PpIX fluorescence imaging and photoacoustic blood oxygen imaging is provided, and the photodynamic treatment effect on different cancers is improved.

Description

technical field [0001] The invention relates to the field of microneedle patch preparation and biomedicine, in particular to a microneedle patch for enhancing PpIX accumulation in solid tumors and a preparation method thereof. Background technique [0002] 5-aminolevulinic acid (5-ALA) is selectively taken up by tumor cells and rapidly biosynthesized into protoporphyrin IX (PpIX) with fluorescent properties, which can be used for fluorescence imaging-mediated tumor diagnosis. Therefore, the photochemical reaction of 5-ALA-based photodynamic therapy (5-ALA-PDT) mainly occurs in cancer cells, avoiding off-target toxic side effects. Although topical 5-ALA-PDT has become the mainstay of treatment for patients with actinic keratosis or basal cell carcinoma, the limited intratumoral biosynthetic concentration of PpIX and short tumor residence time, as well as tumor heterogeneity, tumor hypoxia The characteristics of environment and strong antioxidant system limit the clinical app...

Claims

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Application Information

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IPC IPC(8): A61K41/00A61K9/70A61K47/42A61P35/00A61K49/22A61K49/00A61M37/00
CPCA61K41/0071A61K41/0057A61K9/7023A61K9/0021A61K47/42A61P35/00A61K49/222A61K49/0036A61K49/0056A61M37/0015A61M2037/0053A61M2037/0046A61M2037/0023
Inventor 黄鹏贺港李雅诗林静
Owner SHENZHEN UNIV
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