Construction Of Drug Delivery System Based On Pinus Koraiensis Polysaccharide Gel And Its Anti Breast Cancer Activity Research

The chemotherapy is regarded as the most primary and general method on cancer therapy,and paclitaxel(PTX)is one of effective drug on various solid tumors.Unfortunately,the poor water solubility of PTX limited its availability,Taxol~?,which is composed of Cremophore~?EL/ethanol mixture as the vehicle of PTX,has been used as the only formulation in clinic.However,Cremophore~?EL results in the side effects such as hypersensitivity reaction and peripheral neurophthy.In addition,the intravenous administration for Taxol~?reduces the treatment effect due to its systemic circulation.Therefore,it is a challenge to develop novel PTX administration which limits the use of Cremophore~?EL and has tumor selectivity.To achieve these demands,local drug delivery constructed by implantable or injectable carriers,which can directly administer drugs to tumor tissue,has been proposed as an alternative.The hydrogel is typically used as the carrier in local drug delivery due to its superior advantages such as 3-dimensional structure and sustained drug release behavior.However,the conventional hydrogels require surgical procedure to be implanted into the body,and it accompanies invasive handling and inconvenience to the treatment process.To overcome above problems,the injectable hydrogel which has an ability to recover the gel form after injection into the body has recently attracted much attention.Polysaccharides have been strongly developed as the material to constitute the injectable hydrogel due to their various advantages including wide resources,biocompatibility and hydrophilicity.For decades,chitosan,hyaluronic acid and carrageenan etc.have already been studied as representative gelling agents and finding new sources of polysaccharides is still valuable in terms of developing natural resources and corresponding demands for medical applications.Pinus koraiensis polysaccharide(PKP)is a kind of plant hetero polysaccharide from Pinus koraiensis.Notably,the antitumor activity of PKP was reported,and the development of PKP as anticancer drug carrier is expected to be synergistic.In present work,we reported an injectable hydrogel based on PKP-A(PKA)prepared by simply adding ethanol without any chemical cross link reagents.To our best knowledge,this is the first attempt to develop PKA as a drug carrier.We investigated the characteristics of the PKA gel by FT-IR,SEM and rheology.The injectable performance of PTX-loaded gel was studied in terms of recovery time and rheological properties.The biological properties of PKA gel including biodegradability and hemocompatibility were investigated,and in vitro drug release behavior was simulated.in vitro cellular assays were also measured to estimate the tumor inhibition effect.Finally,in vivo cancer inhibition effect was assessed on 4T1tumor bearing BALB/c mice model.The results of this work suggest that the local PTX delivery constructed by the PKA gel exhibited the enhanced therapeutic effect and reduced systemic toxicity in cancer treatment.