Studies On The Load And Sustained-release Of Methotrexate And Daunorubicin Hydrochloride In Layer-by-Layer Polyelectrolyte Films

Layer-by-layer?LBL?self assembly technique has been wildly used in the field of drug delivery and the preparation of multilayer films because of the simple,effective preparation method and the mildness environment.In this work,polyaspartic acid?PASP?was used as polyanion electrolyte,polyallylamine hydrochloride?PAH?and polydimethyl diallyl ammonium chloride?PDDA?were used as polycation electrolytes to prepare the multilayers with anticancer drugs loaded.The load and release performance of drugs were further investigated in this study and the films were characterized by atomic force microcopy?AFM?.Firstly,LBL multilayer films capable of releasing methotrexate disodium salt?MTX?were fabricated successfully.MTX was conjugated to PAH via electrostatic attraction to produce PAH-MTX compound.Various factors were studied in the fabrication of?PASP/PAH-MTX?*n,results showed that the PASP?pH=4.0?and PAH-MTX?pH=7.5?is appropriate,and the more MTX can be loaded and the longer releasing time can be lasted by increasing the concentration of polyelectrolytes and the number of deposition cycles.Then,MTX was also loaded into?PASP-PAH4.0/PAH7.5?*n film by a post-diffusion process via the electrostatic interaction between MTX and PAH,and the loaded MTX can be released about 15 h under the condition of saline?37??,the amount of medicine release is about 2.4 mg.After that,?PASP4.0/PAH-PASP7.5?*n multilayer films were fabricated by dipping and spraying methods respectively and daunorubicin hydrochloride?DNR?was successfully loaded into them by the post-diffusion method.The influence of layer numbers to load and release of DNR showed that,the more assemble cycles can lead to more DNR moleculars loaded,and the loaded DNR can be released from?PASP4.0/PAH-PASP7.5?*10.5_DNR film about 30 hours,which is longer than 5.5 and 15.5 deposition cycles.The dry operation during DNR loaded can be in favour of a higher loads and a longer releasing time.The films produced by spraying method loaded less DNR moleculars,and the loaded drugs show burst release.In the end,polymeric films capable of loading MTX and DNR at the same time were fabricated.MTX was loaded during the?PASP4.0/PAH-MTX7.5?*n preparation and DNR was loaded by a post-diffusion process.All the assembly process were simple electrostatic attractions only.The load and release of MTX and DNR were further investigated in this work,results showed that,DNR can be released about 7 h and MTX released from 5 h to 120 h,it's a ladder-like release behaviour from?PASP4.0/PAH-MTX7.5?*18_{PASP4.0/PAH-PASP7.5}*15.5_DNR film.In addition,the releasing time of DNR and MTX from?PASP4.0/PAH-MTX7.5?*18_{PASP4.0/PDDA5.5}*15.5_DNR film are about 15 h and 200 h respectively.Results of cell experiment indicated that the dual-drug loaded system is better than the single drug loaded system in inhibiting effect against cancer cells.The present study provides a new way for designing LBL films for differential release of dual drugs.