The Research On Delivery Of Anticancer Drugs By Multi-responsive Cyclodextrin Nanocarriers

In recent years,cancer has been a major threat to human life and health.Traditional cancer treatment methods can prevent specific killing of anticancer drugs in the process of reaching the lesion site and thus have certain toxic side effects on normal cells.The intelligent nano drug carrier can target and release the drug to the lesion site according to the specific difference of the internal environment of the cancer cell and the normal cell,such as temperature,pH and redox,thereby reducing unnecessary side effects.In thispaper,naturalmacromolecule?-cyclodextrin??-CD?,methacrylic dimethylaminoethylester?DMAEMA?,N-isopropylacrylamide?NIPAM?,polyethylene glycol monomethyl ether?CH₃-PEG-OH?,ferrocenecarboxylic acid?FcA?,caprolactam??-CL?and benzimidazole?BM?were used as raw materials to prepare a series of star polymers and guest molecules,which are self-assembled by host and object of cyclodextrin.An environmentally responsive intelligent nano drug carrier was obtained,and drug loading and drug release experiments were carried out using doxorubicin hydrochloride?DOX?,naproxen?NAP?,indomethacin?IND?and diclofenac sodium?DS?as template drugs.Using?-CD,DMAEMA as raw materials,?-cyclodextrin star poly?2-?dimethylamino?ethylmethacrylate???-CD-?PDMAEMA?₇?wasprepared.Amphiphilic polymers were prepared using host-guest recognition of cyclodextrin and self-assembled in aqueous solution to form supramolecular micelles.Benzimidazole protonized from cyclodextrin cavity under acidic conditions led to micelle disintegration and showed good pH sensitivity.The structure,morphology and particle size of supramolecular micelle?-CD-?PDMAEMA?₇/BM-PCL were characterized by fourier transform infrared spectroscopy?FTIR?,transmission electron microscopy?TEM?and laser particle size analyzer.The results demonstrated that the supramolecular micelles exhibit a regular spherical structure with a particle size of about 50-100 nm,which has good temperature and pH response characteristics.The external temperature was raised from 25°C to 45°C and the pH was lowered from 7.0to 2.0.Polymeric micelles increased drug release by 40%and 36%,respectively.The DOX drug loading and encapsulation efficiency were as high as 40%and 86%.The star-shaped polymer?-CD-PNIPAM was prepared by atom transfer radical polymerization?ATRP?.The drug-loaded supramolecular micelle?-CD-?PNIPAM?₇/BM-PCL was prepared by self-assembly with the guest molecule BM-PCL.Due to the unique phase transition mechanism of PNIPAM,supramolecular micelles have good temperature-sensitive properties.Above the low critical solution temperature?LCST?of PNIPAM,the hydrophilic segment of the PNIPAM acting as a shell will agglomerate and shrink,resulting in reduced stability of the drug-loaded micelles,giving it a unique temperature response characteristic.Secondly,BM will protonate out of the cyclodextrin cavity in an acidic solution,giving it a good pH response.The experimental results shown that the particle size of the supramolecular micelles was between 50-100 nm,and the release amount was 40%higher than that at 25°C at 37°C.At pH 5.2,the release amount was also 40%higher than that at 7.The loading efficiency of DOX was 34.97%,and the encapsulation efficiency was 77.21%.When the temperature was higher than the LCST of PNIPAM,?-CD-?PNIPAM?₇/Fc-mPEG supramolecose-loaded micelles with temperature and redox response characteristics were prepared by?-CD host-guest recognition.The chain agglomeration of PNIPAM acts as the hydrophobic core of the micelle,and the hydrophilic mPEG shell increases the stability of the micelle.When the micelles encounter redox stimulation,the Fc was oxidized to the Fc⁺depleted cavity of the cyclodextrin,giving the micelles a redox response characteristic.Subsequent experiments confirmed that the micelles exhibited a regular spherical structure with a drug loading of 37.23%and an entrapment efficiency of 74.45%.The temperature increased from 37°C to 42°C,and the H₂O₂ concentration increased from 0 to 0.3%.?w/w?.The release rate of DOX-loaded supramolecular micelles?-CD-?PNIPAM?₇/Fc-mPEG was significantly increased.This unique drug carrier with temperature and redox response characteristics has a positive guiding effect on the development of future anticancer drugs.