An active oxygen stimulus-responsive nanogel drug carrier and its preparation method and application
A stimuli-responsive, nano-gel technology, which is applied in drug combinations, pharmaceutical formulations, anti-tumor drugs, etc., can solve the problems of poor stability of photosensitizers, weak affinity of photosensitizers, and difficult control of drug loading rate, and achieve mild conditions and raw materials. The effect of easy availability and simple synthesis method
Inactive Publication Date: 2020-06-30
TIANJIN UNIVERSITY OF TECHNOLOGY
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Problems solved by technology
[0010] Although the currently reported photosensitizer delivery carriers can successfully transport photosensitizers and solve the problem of water solubility of photosensitizers to a certain extent, most of these photosensitizer carrier systems are loaded by simple coating or physical adsorption. Photosensitizers, these methods have weak affinity for photosensitizers, resulting in poor stability of photosensitizers in the carrier, difficult to control drug loading rate and unable to achieve controlled release of drugs
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Embodiment
[0040] 1) Synthesis of Active Oxygen Sensitive Crosslinker (MAC-SO)
[0041] Add 855mg salicylaldoxime (SO) into 9.4mL tetrahydrofuran, N 2 atmosphere, placed in an ice-water bath. Add 2.65 mL of triethylamine, then slowly add 2 mL of methacryloyl chloride (MAC), and keep the reaction temperature below 5°C during the dropwise addition. The dosage ratio of salicylaldoxime to methacryloyl chloride is 1:3. 10 minutes after the dropwise addition, the reaction was stopped. Spin the reactant to dryness, add chloroform to dissolve, wash twice with water with pH = 8, then wash with pure water or saturated saline until neutral, dry the organic phase with anhydrous sodium sulfate, filter with suction, spin dry, and pass the crude product through the column Purified by chromatography, the eluent was n-hexane:ethyl acetate=1:1, and MAC-SO was obtained. Structure: 1 H NMR (400MHz, CDCl 3 )δ8.49(d, J=11.1Hz, 1H), 8.04(dd, J=7.9, 1.4Hz, 1H), 7.50(td, J=8.2, 1.6Hz, 1H), 7.29(dd, J=15.9 ...
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The invention relates to a preparation method and application of a photosensitizer transmission carrier sensitive to active oxygen. According to the preparation method and application, salicylaldoximeand derivatives of the salicylaldoxime serve as cross-linking agents, vinylpyridine and polyethylene glycol serve as monomers to perform free radical polymerization, and then obtained nanoscale particles can serve as the transmission carrier of a photosensitizer. After the photosensitizer is transmitted to a lesion position, the cross-linking agents can fracture to release the photosensitizer tothe lesion position when being subjected to active oxygen stimulation generated by the photosensitizer. The preparation method and application of the photosensitizer transmission carrier sensitive tothe active oxygen have the advantages that the preparation method of the carrier is simple, the raw materials are obtained easily, the water solubility problem of the photosensitizer can be effectively improved, the drug administration on the lesion position 'according to demands' is achieved, the biological distribution of the drug on the tumor is improved, the toxic and side effect of the drug is obviously reduced, and then the better curative effect than original medicine is obtained. The preparation method and application of the photosensitizer transmission carrier sensitive to the activeoxygen have an important practical prospect and social value in the fields of oncotherapy and drug delivery.
Description
technical field [0001] The invention belongs to the field of drug carriers, in particular to a preparation method and application of a reactive oxygen stimulus-responsive nanogel as a photosensitizer delivery carrier. Background technique [0002] Malignant tumors have become one of the most serious diseases that threaten human health and cause human death. However, traditional cancer treatment methods in clinical medicine include surgical resection, radiotherapy, and chemotherapy. In recent years, photodynamic therapy has attracted extensive attention of researchers. Compared with traditional cancer treatment methods, photodynamic therapy has the following advantages: (1) selectively kills focus cells without harming surrounding normal tissues. (2) The photosensitizer has no special toxicity to the human body and no interaction with other drugs, and can be used in combination with other treatment methods. (3) There is no cumulative drug toxicity, and repeated treatment is...
Claims
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IPC IPC(8): C08F290/06C08F226/06C08F222/22A61K41/00A61K47/32A61P35/00
CPCA61K41/0057A61K47/32C08F290/062C08F226/06
Inventor 陆燕赵琳琳石鲁清
Owner TIANJIN UNIVERSITY OF TECHNOLOGY