Design,Synthesis And Bioactivity Studies Of Dual-target Nanodrug Based On Natural Active Molecules Camptothecin And Podophyllotoxin

Both in medicines and pesticides,combination with two or more drugs has many distinctive advantages that are not available with single drug agents:promoting synergism among the different drugs against cancer cells or insect and suppressing drug resistance through distinct mechanism of action.Nanotechnology has been developed as a powerfull tool for drug delivery and widely applied in the areas of medicines and pesticides.Dual-target nano-drug is nanotechnology-based combination with two drugs,getting attention in medicines,and could be considered as an emerging approach for the treatment of cancer in near future.However,thus far there are no papers about nanotechnology-based combination with two or more pesticides.Taking this into consideration,our group conjugated the botanic pesticide camptothecin with polyethylene glycol,forming amphiphilic copolymer.The conjugate could be self-assemble into micelles,or forming a hydrogel with a-CD by super-cross-linked to combine delivery with acetamiprid or nitenpyram.These two double-target nano-pesticide are evaluated for their insecticidal activity against T.Cinnabarinus,B.brassicae,and B.xylophilus.The results show that these two double-target nano-pesticide could significantly improve the insecticidal activity,compared with two parent pesticides.It implied that there is synergism between camptothecin and acetamiprid or nitenpyram.Slow-release formulations can decrease the applied amounts of pesticides and prolong and better control release of drug,and have been the focus of research about drug delivery systems.Mesoporous silica materials have the potential to be widely used as drug carriers due to their nontoxic nature and drug-releasing properties.Our group prepares mesoporous silica nanoparticles using amphiphilic copolymer(CPT-PEG and AVM-PEG)and cetyltrimethylammonium bromide(CTAB)as dual templates.In vitro release study shows this formula can continuously release within 25 days.This formula is evaluated for their insecticidal activity against B.xylophilus,T.Cinnabarinus,and P.xylostella.The results show that the formula could improve the insecticidal activity,compared with two parent pesticides.It implied that this formula could suppress avermectin resistance.Colon-specific drug delivery is recognized to be advantageous in the treatment of disorders of the large intestine,such as irritable bowel syndrome,colitis and colon cancer where it is necessary to attain a high concentration level of active agent in the large intestine.Colon delivery can also offer a benefit over orally administered drugs which exhibit poor uptake in the upper regions of the gastrointestinal tract due to degradation by the luminal or mucosal enzymes.Due to luxuriant microbial glycosidases and azoreductases,Polymeric colon delivery systems designed for bacterial degradation were based on hydrolysis of polysaccharides or azo bond reduction.Furthermore,the low-toxic dose of 5-Fu has an additive or even more-than-additive effect on the cytotoxicity induced by GL331 at 0.1 μM or less.Taking this into consideration,we design to prepare supramolecular hydrogels encapsulating GL331 as colon dual-targeting drug delivery carrier and evaluate the synergistic effect with 5-Fu.Maybe the strategy could extend the clinical application of GL331.In vitro release study shows this formula can continuously release within 5 days.