Study On Chitosan Hollow Microspheres Based On Schiff-base Bond As Efficient Drug Carrier

It is well-known that anticancer drugs are mostly lipophilic macromolecules.Their poor water solubility limited their efficacy,thus a serious challenge is posed to anticancer drugs for application.In addition,high toxicity of naked drugs and low bioavailability are also problems.To address these issues,a wide variety of drug carriers have been proposed.Though numerous drug carrier systems,such as liposomes,polymeric micelles,microspheres and nanoparticles,have become popular types in biomedical applications,scientists still have a common goal:to design safer and more effective carrier for those tough anticancer drugs.Chitosan is a natural alkaline polysaccharide with good biocompatibility,biodegradability,nontoxic and transmembrane ability.It has been widely used for many pharmaceutical and medical applications.Its cationic property causes it to approach cell membranes more easily,and changes the permeability of cell membranes.Therefore,many drug carriers are designed on the basis of chitosan and its derivatives.Herein,we contribute a new strategy to fabricate chitosan hollow microspheres(CHM)via an O/W emulsion interfacial Schiff-base bonding reaction.We employ numerous hydrophobic small molecules of borneol 4-formylbenzoate(BF)to fix water-soluble hydrophilic biomacromolecule of glycol chitosan(GC),forming the CHM with a positively charged surface and lipophilic cavity,which is a suitable drug carrier for water-insoluble anticancer drugs,such as paclitaxel(PTX).The CHM was characterized by a series of analytical techniques,suggesting the CHM was successfully synthesized.Both cell uptake and cell cytotoxicity assays in vitro indicated that the PTX-loaded CHM was highly efficient on cancer cells.The main contents and results are as follows:1.The borneol 4-formylbenzoate(BF)was successfully synthesized via esterification between borneol and 4-formylbenzoic acid.2.The CHM was fabricated by employing O/W emulsionan interfacial Schiff-base bonding reaction,coumarin-6(Cou-6)and PTX were successfully encapsulated used as model of lipophilic drugs.These CHM have an average size of 400-000 nm after passing through the 0.22μm microporous membrane.Exactly,this phenomenon combined with SEM measurements demonstrates its remarkable shape-adaptive behavior.3.The CHM present a pH-dependence of structural stability.When pH value reduces from 7.06 to 5.01,the CHM began to lose their integrality.While,PTX cumulative release amount significantly increased to approximately 76.8%at pH 5.01 over 48 h,going with a fast release rate.4.The anti-tumor effect of CHM was studied by in vitro cell experiments.In vitro cellular uptake analyses displayed for the first time the real-time phagocytosis of the CHM and the in-situ intracellular release of the loaded fluorescent molecules.MTT assays further demonstrated good efficacy of the PTX-loaded CHM.In summary,these CHM are successfully prepared by employing O/W emulsionan interfacial Schiff-base bonding reaction with high drug loading efficiency,smart capabilities and high efficiency,shape-adaptive and pH responsive features,and effective anti-tumor effect.Since this unique assembly strategy supplies advantages such as facile fabrication,low cost but high efficiency to form intelligent drug carrier,we believe this adaptive CHM show great potential as a novel drug carrier,and this CHM model would open a new avenue for tough drugs on treating tumors.