Preparation and application of protein adsorption-resistant photic sensitivity-enhanced anoxic stress cationic carrier

A technology of anti-protein adsorption and cationic carrier, which is applied in the light-sensitized hypoxic stress cationic polymer as a drug delivery carrier. In the field of preparation of the carrier, it can solve the problem of shortening the half-life of blood and achieve aggravation of hypoxia and accelerated drug delivery. Release and promote the effect of tumor accumulation

Inactive Publication Date: 2018-05-04
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, after multiple applications of PEG, it will cause obvious humoral immune response. After the neutralizing antibody secreted by B cells binds to PEG, the PEG-modified carrier will be recognized and cleared by phagocytes, and its blood half-life is significantly shortened, that is, PEG has ABC (accelerated blood clearance) effect

Method used

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  • Preparation and application of protein adsorption-resistant photic sensitivity-enhanced anoxic stress cationic carrier
  • Preparation and application of protein adsorption-resistant photic sensitivity-enhanced anoxic stress cationic carrier
  • Preparation and application of protein adsorption-resistant photic sensitivity-enhanced anoxic stress cationic carrier

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Embodiment 1

[0038] Preparation of PEI derivatives modified by embodiment 1 sultaine

[0039] Dissolve 0.4g PEI (MW 1800) in methanol solution, add 0.27g carboxybetaine monomer, react for 1-3 days, dialyze (MWCO=1kD) for 48-72h, freeze-dry to obtain sulfobetaine-PEI derivative ( D. 14％ -PEI).

Embodiment 2

[0040] The preparation of the polylysine derivative of embodiment 2 carboxybetaine modification

[0041] 0.5g polylysine (MW 10000) is dissolved in the mixed solution of N,N-dimethylformamide and methanol (v / v=1:1), adds 0.34g carboxybetaine monomer, reaction 1- 3 days, dialyzed (MWCO=3.5kD) 48-72h, lyophilized to obtain sulfobetaine-polylysine derivative (D 20％ -PLL).

Embodiment 3

[0042] The preparation of embodiment 3 sultaine modified hydroxyethyl chitosan derivatives

[0043] Dissolve 0.1g of hydroxyethyl chitosan in a mixed solution of dimethyl sulfoxide and methanol (v / v=1:3), add 0.59g of sulfobetaine monomer, react for 1-3 days, dialyze (MWCO =14kD) 48-72h, freeze-dried to obtain sulfobetaine-hydroxyethyl chitosan derivative (D 30％ -HECS).

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Abstract

The invention belongs to the field of pharmaceutic preparations, and discloses the preparation and pharmaceutical application of a protein adsorption-resistant photic sensitivity-enhanced anoxic stress cationic carrier. A cationic polymer is taken as a skeleton to modify a zwitter-ion glycine betaine monomer so as to weaken the adsorption to protein in an organism of the polymer; further modifyingthe intermediate with a hydrophobic connecting arm containing an anoxic stress azobenzene structure and a photosensitizer, so as to construct an amphipathic polymer carrier. The cationic modifier form a nanoparticle through self assembling in a water solution, can be directly applied to photodynamics therapy, can also be used for loading hydrophobic chemical drugs or nucleic acid drugs and applied to photodynamics and antineoplastic drug combination therapy. According to the invention, the photodynamics therapy of the photosensitizer is used for constructing a high-anoxic tumor microenvironment to stimulate nanometer disassembly, thus promoting drug release and improving the utilization ratio; in addition, through the sensitivity-enhanced antineoplastic drug therapeutic effect generated by the photodynamic active oxygen, the high-efficient synergistic treatment on tumour is realized.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and relates to a light-sensitized anoxic stress cationic polymer resistant to protein adsorption as a drug delivery carrier, and also relates to a preparation method and application of the carrier. Background technique [0002] Photodynamic therapy (Photodynamic therapy, PDT) is an important non-invasive treatment method, which has been applied in the clinical application of tumor treatment; After light, it becomes an excited state molecule, which reacts with oxygen to generate singlet oxygen, which can effectively kill tumor cells. PDT has gradually become the fourth minimally invasive therapy for tumor treatment after surgery, radiotherapy and chemotherapy. Compared with other traditional anti-tumor treatments, PDT has many advantages such as cancer cell specificity; photosensitizer molecular safety, does not inhibit human immune function; drug resistance is not easy to develop. How...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K41/00A61K45/00A61K47/58A61K47/64A61K47/61A61P35/00
CPCA61K41/0057A61K45/00A61K2300/00
Inventor 霍美蓉殷婷婕梁金来
Owner CHINA PHARM UNIV
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