Study On Layered Double Hydroxides As Drug Delivery System And The Release Property Of Drug From Nanohybrids

Nowadays one of the important research content in the research field of drug delivery system is research and development of the drug delivery materials.The perfect drug carrier should have advantages in the aspects of its bioavailability,biodegradability, biostability,reduced toxicity and the high drug loading.Recently,layered double hydroxides(LDHs)have been reported as a new delivery system for many anionic drugs via ion-exchange and some poorly water-soluble drug molecules via methods of coprecipitation,assemblage and reconstruction.Therefore in order for poorly water-soluble drug therapy to be more effective,the research on the property of LDHs as drug delivery material is very important.Among those poorly water-soluble drugs,camptothecin(CPT)is a typical antitumor model.We chose CPT as the guest molecule and Mg-Al LDHs as the host material to synthesize CPT-LDHs nanocompounds via methods of assemblage and reconstruction. The effect of reaction conditions on the drug loading were examined.Powder X-ray diffraction(PXRD),TEM,SEM and FT-IR spectroscopy were used to characterize the achieved products.Release mechanism and kinetics of CPT from nanohybrids were investigated as well.Main contents and conclusions:1.Synthesis and characterisation of Mg-Al LDHsThe purpose of this part is to synthesize the pristine material LDHs.The pristine Mg-Al LDHs was prepared by coprecipitation method from mixed solution of Magnesium and Aluminum chloride hexahydrates,The effects of the molar ratio of MgCl₂6H₂O/AlCl₃6H₂O on M³⁺/[M²⁺+ M³⁺]molar ratio x and the lattice parameter were investigated.The results show that Mg/Al molar ratio of the syntheized product was lower than that of the raw mixed salt solution,the reason for which was that the solubility product of Mg(OH)₂ is lower than that of Al(OH)₃. x is between 0.19～0.36,a is between 0.304～0.308nm,c is between 2.306～2.4nm,d is between 0.767～0.799nm,the interlayer space is about 0.30nm.The achieved product consisted of the typical thin,hexagonal plate-like crystals with～100 nm in size.2.Synthesis and charaterisation of CPT-LDHs-SDS nanohybrids(1)The method of assemblage was used to syntesize the nanohybrids.During the process the Mg/Al ratio x of Mg_xAl/DS LDHs,the polarity of the solvents,initial CPT concentration(C_CPT)and contact time in the intercalation process were studied to investigate their effects on the amount of CPT loaded into CPT-Mg_xAl LDHs-SDS nanohybrids(A_in).The most effective uptake of CPT occurred in DMSO media by Mg₃Al LDHs-SDS.The maximum A_invalue reached about 5.2%(w/w)under studied conditions.(2)The release rate of CPT from the nanohybrid at pH 7.2 is remarkably lower than that at pH 4.8,this is due to a possible difference in the release mechanism.For the pH 7.2 release,the mechanism is primarily through diffusion of drug molecules;while for the pH 4.8 release,that is through both the dissolution of LDH layers and diffusion of drug molecules among which the former one is dominating.The release kinetics of CPT from the nanohybrids obeyed the pseudo-first order kinetic model.3.Synthesis and charaterisation of CPT-LDHs nanohybrids(1)The method of reconstruction was used to syntesize the nanohybrids in ethanol-water mixed solution.During the process the volume ratio(R_v)of ethanol/water, initial CPT concentration(C_CPT),the reaction temperature and contact time in the intercalation process were studied to investigate their effects on the amount of CPT loaded into CPT-LDHs nanohybrids(A_in).The maximum A_invalue reached about 14% (w/w)when R_v=7:3 after 24h reconstruction under 60℃.(2)According to the size of CPT molecule and the gallery height of the nanohybrid,a probably arrangement of CPT molecules in CPT-LDHs nanohybrid may be proposed, i.e.,CPT molecules arrange as monolayer with their long axes parallel to the LDHs layers.(3)The release rate of CPT from the nanohybrid at pH 7.2 is remarkably lower than that at pH 4.8,this is due to a possible difference in the release mechanism.For the pH 7.2 release,the mechanism is primarily through diffusion of drug molecules;while for the pH 4.8 release,that is through both the dissolution of LDH layers and diffusion of drug molecules among which the former one is dominating.The release kinetics of CPT from the nanohybrids obeyed the pseudo-second order kinetic model.(4)we successfully attached disuccinimidyl carbonate(DSC)to the LDHs surface and achieved the surface functionalization of LDHs.