Preparation,Modification And Characterization Of Paclitaxel Nanohybrids Based On LDHs

Paclitaxel(PTX)is a nonionic hydrophobic anticancer drug,showing significant antitumor activity against a variety of cancers such as ovarian,breast,and lung cancer.However,the clinical application of PTX has been limited because of its poor water solubility,low bioavailability,and strong toxic side-effects.Therefore,it is very necessary to develop its delivery and controlled release systems.Layered double hydroxides(LDHs)are one of promising drug carriers that have recently received great interest.Drug molecules can be intercalated into their interlayers,forming drug-LDHs nanohybrids with good drug delivery and sustained release performance.However,there are some problems need to be solved,such as the extremely low loading of hydrophobic drugs and the poor dispersion stability of the durg-LDHs nanohybrids in water.In the current work,PTX was chosen as a model of nonionic,poorly water-soluble drugs,and a co-assembly route was used to construct PTX-LDHs nanohybrids,to explore the suitable strategy for the effective loading of hydrophobic drugs.The so-obtained nanohybrids were modified using a liposome(LS)-coating strategy,forming(drug-LDHs)@LS nanocomposites,to enhance the dispersion stability of drug-LDHs nanohybrids.The drug release behavior of the nanohybrids and nanocomposites was determined,to evaluate the prospect of their application as drug release systems.This work may provide useful information for developing PTX sustained release formulations based on LDHs.Main research contents and conclusions:(1)Preparation,modification and characterization of PTX-sodium cholate-LDHs nanohybrids.PTX-LDHs nanohybrids were prepared by a "drug modification/co-assembly"method.PTX molecules were first incorporated into sodium cholate(Ch)micelles,and the PTX-loaded micelles were then co-assembled with positively charged LDH single-layer nanosheets(SLNSs),forming PTX-Ch-LDHs nanohybrids.The nanohybrids were coated with LSs using a reverse evaporation method,forming(PTX-Ch-LDHs)@LS nanocomposites.The crystal structure,morphology,interfacial electrical property,and thermal stability of the samples were characterized using XRD,TEM,FT-IR,TG/DSC,and Zetapotential measurement techniques.The water dispersion stability and drug release behavior of the samples were determined.The drug loading of PTX-Ch-LDHs nanohybrids is?5.12 wt%.No obvious aggregation occurs for the(PTX-Ch-LDHs)@LS nanocomposites in water,and their average particle size is?300 nm.The nanocomposites exhibit a better drug sustained-release performance than the nanohybrids.The results demonstrate that the drug-modification/co-assembly method can realize the effective loading of hydrophobic drugs on LDHs,and that liposome-coating can significantly improve the water dispersity and sustained-release performances of drug-LDHs nanohybrids.The(PTX-Ch-LDHs)@LS nanocomposites are a promising drug release system.(2)Preparation,modification and characterization of PTX-graphene oxide-LDHs nanohybrids.PTX-graphene oxide(GO)-LDHs nanohybrids were prepared using a co-assembly route.PTX molecules were first loaded on GO nanosheets,and the drug-loaded GO nanosheets were then co-assembled with positively charged LDH SLNSs,forming PTX-GO-LDHs nanohybrids.The drug loading of the nanohybrids is?5.0 wt%,indicating that the method can realize the effective loading of hydrophobic PTX on LDHs.The so-obtained nanohybrids were coated with LSs,forming(PTX-GO-LDHs)@LS nanocomposites.The resultant nanocomposites in water show good dispersed spherical particles with les's than 200 nm in size,indicating that the LS-coating can obviously improve the dispersion stability of the nanohybrids.In addition,the PTX-GO-LDHs nanohybrids exhibit a good drug sustained release performance,and the drug release process can be described by the pseudo-second-order kinetic model.The(PTX-GO-LDHs)@LS nanocomposites are a promising drug delivery system.