Study On Layer-by-Layer Assembled Films For Antibiotics And Anti-tumor Drugs Delivery

In recent years,with the rapid development of nanotechnology,nano drug delivery carrier has become one of the hot spots in nanomaterials and has a high application value in the medical field.The study of single drug carrier has been relatively mature,research on dual drug or multi-drug delivery system has attracted wide attention.Layer-by-layer assembly nanoparticle film based on non-covalent force between polyions.There are many advantages such as mild conditions,simple operation,different drugs are loaded with various ways.Based on the above,in this paper,LBL assembly technology is used to prepare two kinds of dual drug delivery system,which loading antibiotics and anti-tumor drugs,with non-toxic,good biocompatible and biodegradable polyelectrolytes.One of systems is to complete the common load of two positively charged drugs,the other is to achieve a dual drug load with different charge.This study provides an experimental basis for the new dual drug delivery system.First,Layer-by-Layer assembly multilayer films was fabricated to release two kinds of positively charged drugs such as Vancomycin hydrochloride?VAN?and Daunorubicin hydrochloride?DNR?.VAN was loaded into films by first complexing with polyaspartic acid?PASP?to prepare PASP-VAN complexes,and then PASP-VAN was LbL assembled with chitosan quaternary ammonium?HTCC?to fabricated?PASP-VAN/HTCC?*10 multilayer films.The effect of PASP-VAN and polyelectrolyte HTCC pH on the VAN loading was studied,and the optimum pH condition was(PASP-VAN_4.0/HTCC_8.0)*10.The release time of VAN from the film(PASP-VAN_4.0/HTCC_8.0)*10 was 1650 min in the LBL way.Then DNR was loaded into(PASP-VAN4.0/HTCC_8.0)*10 films by a post-diffusion process,and two kinds of positively charged drugs were loaded into one multilayer films DNR-(PASP-VAN_4.0/HTCC_8.0)*10.It was shown that in physiological saline at 37?,the release time of DNR and VAN were 540 min and 720 min.The surface morphology were characterized by atomic force microscopy?AFM?,the surface roughness of the substrate ?the film of(PASP-VAN_4.0/HTCC_8.0)*10 and the film of DNR-(PASP-VAN_4.0/HTCC_8.0)*10 increased in turn.Secondly,The effect of barrier layer on drugs release was studied.In order to slow down the release rate of antitumor drug DNR,the dual drug system was combined with barrier layer.The film(PASP_4.0/HTCC_8.0)*20 was fabricated,DNR was firstly loaded into films by a post-diffusion process.Then the capping layers?PASP/PAH?*n were assembled by using spray-coating method and LbL assembly method.The second drug VAN was loaded by complexing with PASP to prepare PASP-VAN complexes,and then PASP-VAN was deposited with HTCC to prepare the dual drug delivery system.Research shows that the 10 T barrier layers were prepared in the two methods has little difference in the blocking effect,but the efficiency of the spray method is high.The effect of the numbers of the capping layers with spraying on the release time of DNR was studied,research shows that the capping layers could effectively slow down the release rate of DNR,and the release time of DNR was prolonged more than 2310 min because of 20 cycles barrier layer while the release time of DNR was extended more 420 min because of 10 cycles barrier layer.The release experiment of dual drug delivery system indicated that,VAN released 1680 min and DNR released last for 2700 min.Finally,The oppositely charged drugs of antibiotic ceftriaxone sodium?CTX?and DNR were used in the experiment.The multilayer film(HA_4.0/PAH-CTX7.5)*6 was fabricated by LbL assembly of Sodium hyaluronate?HA?and Polyeletrolyte complexes?PAH-CTX?.Then the blank film(PASP_4.0/PDDA)*20 was papred in the surface of this film,and DNR was loaded into it by a post-diffusion process.In order to slow down the release rate of DNR,the capping layers?PASP/PAH?*20 were assembled on the films by using spray-coating.The release experiment of dual drug delivery system indicated that,CTX released 9 h,and DNR released last for 81 h.The rapid release of antibiotics CTX help to kill bacteria in time,long-term release of anti-cancer drug DNR help reduce the toxic side effects on normal tissue.