Preparation And Characterization Of Novel Cerasome And Mesoporous Silica Based Functional Drug Delivery System

Nano carrier attracted more and more attention in rcent years mainly for its advantages caused by small size effect,highly improved drug solubility,controlled drug release and targeted delivery,its of great usage in improving drug pharmacokinetics and pharmacodynamics.As one of the most fashionable subject of research,cerasome is a liposome-resembling bilayer vesicle with extraordinary stability and without premature drug release.Mesoporous silica nanoparticles,high specific surface area give it a high drug loading capacity,its special mesopores can be used for drug controlled release.This thesis mainly focused on the development of novel cerasome and mesoporous silica for controlled drug release or further theranostic.1.Preparation and characterization of a novel nanocomposite:silver nanoparticles decorated cerasomeIn this study,a novel artificial hybrid vesicle,nano silver particles decorated cerasome were fabricated through sol-gel and self-assemble methods as well as in situ reduction.Samples were characterized in terms of hydrodynamic size and surface morphology via dynamic light scattering(DLS)as well as scanning and transmission electron microscopies.Analysis through energy dispersive X-ray spectrometer(EDS)proved the existence of silver particles.Due to the high morphological stability of cerasome,Silver nanoparticles with a size of about 5?10nm can be deposited on the surface without any stabilizers.The UV spectra revealed a single symmetric extinction peak at 406nm,confirming the spherical shape of the synthesized silver nanoparticles.Several reducing agents were screened before confirming sodium borohydride(NaBH4).Comparison of different NaBH4/lipid ratios(KNaBH4/CFL)was then carried out in order to ascertain its effect.Investigation of the stability of this hybrid vesicles was carried out,indicating that it can be stored at 4? for at least 3 months without any morphological change.Results demonstrated that this hybrid vesicle has excellent morphological stability,which impart it significant potential for various applications such as being an antibacterial material and a radio sensitization agent.2.Redox responsive liposomal nanohybrid cerasomes for intracellular drug deliveryCerasome is a freshly developed bilayer vehicle that resemble traditional liposome but has higher morphological stability.In this study,a novel redox-responsive cerasome(RRC)was developed for tumor-targeting drug delivery.The cerasome-forming lipid(CFL)that comprise a cleavable disulfide bond as connector unit of the triethoxysilyl head and the hydrophobic alkyl double chain was synthesized and subsequently used to prepare cerasome through ethanol injection method.RRC that has liposome-resembling lipid bilayer structure was proved being outstanding at drug loading capacity as well as morphological stability as compared to conventional liposomes.In addition,in vitro drug release tests of DOX/RRCs showed a redox-responsive drug release profile:accelerated DOX releasing compared to reduction-insensitive cerasomes(RIC)in the presence of 10 mM of GSH.Under the same condition,the reduction sensibility of RRC was further proved by increased hydrodynamic diameter and destroying of integrity from DLS and SEM results.RRC showed non-toxic to human embryonic kidney 293 cells,indicating that this material has good biocompatibility.On the other hand,DOX/RRCs showed a resemble IC50(half inhibitory concentration)value to that of free DOX to human hepatoma SMMC-7721 cells and breast cancer MCF-7 cells.IC50 values at 48 h were found to decrease in the following order:DOX/RIC>DOX/RRC>DOX.Taken together,the RRC developed in this study is of great potential to be utilized as a promising platform for intracellular anticancer drug delivery system.3.Layer-by-layer construction of lipid bilayer on mesoporous silica nanoparticle to improve its water suspensibility and hemocompatibilityMesoporous silica nanoparticle(MSN)was expected to provide a versatile drug delivery platform with modification flexibility.To improve its hemocompatibility and realize controlled and/or targeting drug release,modification of bare MSNs is essential.Herein,a novel method of coating MSNs with lipid bilayers was developed.First,a homemade organosiloxane precursor was used for hydrophobic modification of MSNs,then phospholipids(DPPC and DSPE-PEG2000)were coated by a filming-rehydration method based on hydrophobic interaction.The nanoparticle samples were characterized by TEM,DLS,nitrogen sorption,FT-IR,and TGA.Furthermore,the novel lipid bilayer coated MSNs(l-MSNs)were compared with bare MSNs in terms of suspension stability,drug release,hemolysis and nonspecific protein absorption.Our data proved that l-MSNs had better hemobiocompatibility and controlled drug release properties than that of bare MSNs.4.Synthesis of zinc phthalocyanine bridged periodic mesoporous organosilica for combination of cancer chemotherapy and photodynamic therapyA PMO precursor compound was synthesized by conjugation of TCPC with four APTES molecules,then a zinc phthalocyanine bridged periodic mesoporous organosilica was produced by co-condensation of the precursor with TEOS using CTAB as template agent.The PMO should serve as a promising theranostic agent for cancer therapy by combining of optical property of phthalocyanine and drug loading capacity of porous materials.PMO showed no difference in morphology and microstructure with mesoporous material and a considerable singlet oxygen generation under irradiation with 675 nm laser light.