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Protein-based delivery system for overcoming resistance in tumour cells

A tumor cell, drug resistance technology, applied in anti-tumor drugs, nanotechnology for sensing, pharmaceutical formulations, etc., can solve problems such as limiting the success of tumor chemotherapy, and achieve the effect of increasing cytotoxicity and easy modification.

Inactive Publication Date: 2009-01-14
LTS LOHMANN THERAPIE-SYST AG
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  • Abstract
  • Description
  • Claims
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Problems solved by technology

This phenomenon considerably limits the success of tumor chemotherapy

Method used

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  • Protein-based delivery system for overcoming resistance in tumour cells
  • Protein-based delivery system for overcoming resistance in tumour cells
  • Protein-based delivery system for overcoming resistance in tumour cells

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Embodiment

[0068] To prepare nanoparticles according to the present invention, 20.0 mg of human serum albumin and 1.0 mg of doxorubicin hydrochloride corresponding to a molar ratio of 5:1 (active agent: protein) were dissolved in 1.0 mL of ultrapure water, and stirred Simultaneously incubate for 2 hours. When 3.0 mL of 96% ethanol was added through the pump system (1.0 mL / min), serum albumin precipitated in the form of nanoparticles. The above materials were crosslinked for 24 hours by adding different amounts of 8% glutaraldehyde to different degrees (Table 1). The stabilized nanoparticles were divided into 2.0 mL aliquots and purified by 3 cycles of centrifugation and redispersion in an ultrasonic water bath. Supernatants from each washing step were collected and assayed for the fraction of unbound doxorubicin contained therein by RP18 HPLC. To determine the concentration of nanoparticles, 50.0 μL of the formulation was added to a weighted metal boat and dried at 80° C. for 2 h. Aft...

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Abstract

The invention relates to nanoparticles, the particle matrix of which is based on at least one protein in which at least one active agent is embedded, a method of production of the nanoparticles with at least one active agent embedded in t the protein matrix and the use of said nanoparticles for the treatment of tumours, in particular, for the treatment of tumours which are resistant to chemical medicaments.

Description

Background technique [0001] The development of drug resistance in the treatment of solid tumors poses a major problem in oncology. Drug resistance frequently occurs due to increased excretion of chemotherapeutic substances by tumor cells. The mechanism of this drug resistance development is related to the overexpression of P-glycoprotein (Pgp) [Krishna et al., (2000), Eur. J. Pharm. Sci. 11, 265]. Pgp is an ATP-dependent efflux pump that can actively expel medicinal substances from tumor cells. Overexpression of Pgp results in reduced intracellular accumulation of chemotherapeutic agents such that their intracellular concentration is insufficient for antitumor effects. Dosage adaptation of cytostatics, ie, dose increases, is required to compensate for decreased chemotherapeutic aggregation, but is limited due to the toxic side effects of cytostatics that accompany such increases. Overexpression of Pgp leads to so-called multidrug resistance [multidrug resistance, MDR], in w...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/16A61K9/51
CPCA61K9/1658A61K9/5169A61K9/5192A61K9/0019A61P35/00A61K9/16A61K9/51B82Y15/00
Inventor 塞巴斯蒂安·德莱塞克劳斯·朗热约尔格·克罗伊特尔马丁·米歇利斯英德日赫·奇纳特尔
Owner LTS LOHMANN THERAPIE-SYST AG
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