Delivery system for specifically targeting cancer cells and method of use thereof
A specific, cancer cell technology for delivery systems and cancer therapy that addresses high levels of toxicity in healthy tissues
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Embodiment 1
[0133] Embodiment 1: Preparation of planetary ball mill nanoparticles
[0134] First, 10% to 15% (w / v) of alginate, cellulose, collagen, starch, lactose, other biopolymers, or mixtures thereof (excipients / biopolymers) are dissolved in water and Mix using a homogenizer. Next, 10% to 20% (w / v) of proteins (such as BSA or IgG) or macromolecules (such as gadolinium, paclitaxel, and cisplatin, etc.) (w / v) were added to the vehicle / biological in the polymer solution. Next, 10% PEG (w / v) was added to the biopolymer-cytotoxic agent solution and stirred for 30 minutes. After centrifugation, pour the solution into about 3mm 3 tablet press and dry. The tablets were then ground with a planetary ball mill under controlled temperature conditions (<37°C). The resulting particles can be used alone (ie uncoated) or by coating with 5%, 10% or 20% PCL solution (in dichloromethane) under continuous stirring at 1000 rpm. Finally the PCL coated biopolymer-PEG particles were rinsed with wate...
Embodiment 2
[0155] Example 2: Tumor-associated antigen ligand coating and PBM nanoparticles loaded with chemotherapeutic agents for breast cancer cells grain
[0156] Polycaprolactone-polyethylene glycol copolymer for coupling to folic acid coated ~20 nm diameter cytotoxic drug-loaded biodegradable planetary ball mill (PBM) nanoparticles. The folate-coated PBM nanoparticles were further loaded with docetaxel, carboplatin or cisplatin. Incubation of primary cells and cell lines with cisplatin solution at 20 μM resulted in >90% of BrCa cells (MCF-7, MDA-MB-231 and 4T1) and normal (primary) mammary epithelial cells after 24 hours of culture of cell death. However, PBM nanoparticles containing 10-fold less chemotherapeutic agent were taken up and induced apoptosis in BrCa cells, but not primary mammary epithelial cells, at the same level as cisplatin, docetaxel, or carboplatin solutions, respectively. Furthermore, mammary tumor-bearing mice receiving cisplatin solution (8 mg / kg / week) or...
Embodiment 3
[0165] Example 3: Effect of tumor cell targeting and chemotherapy-loaded PBM nanoparticles on prostate cancer cells
[0166] Cytotoxic drug-loaded biodegradable PBM nanoparticles of ~20 nm diameter were coated with polycaprolactone-polyethylene glycol copolymer and folic acid. Treatment of PCa cells (PC3 and PTEN-CaP2) and normal prostate epithelial cells (PrEC and RWPE-1 ) with 20 μM cisplatin resulted in >90% cell death. PBM nanoparticles containing 100-fold less cisplatin were absorbed and induced apoptosis in prostate cancer cells at the same level as cisplatin solution, but did not significantly affect normal cells. Tumor-bearing mice receiving either cisplatin solution (8 mg / kg / week) or folate-coated PBM nanoparticles (containing an equivalent dose of 0.08 mg / kg / week cisplatin) produced significant (and similar) tumor regression. However, mice receiving cisplatin solution had significantly higher renal and hepatic toxicity than native or PBM nanoparticle-treated mice....
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Abstract
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