Preparation And Related Properties Of Novel Drug Carriers For Overcoming Dense Cells

Polymeric micelles have a wide range of applications in the field of drug carriers because then can reduce the side effects of drugs while increasing the dose of the drugs,enhance the circulating time of drugs in the blood,provide a sustained and controlled release.In addition,they can be loaded with multiple drugs for combined therapy.In contrast,traditional nanomaterials can not be rapidly released at designated sites due to their passive transport,which greatly limited their applications.Central nervous system diseases such as Parkinson's disease etc.may lead to very high mortality rates.To overcome the blood-brain barrier(BBB)is an important research bottleneck of the treatment of central nervous system diseases.Overcoming the blood-brain barrier has been extensively studied in recent years,however,biocompatibility and biosafety may be improved.Therefore,the development of new drug carriers to overcome BBB has a very important practical significance.Firstly,we prepared a novel targeted peptide-linked polyethylene glycol modified hydrophobicity(Peptide12-PEG-HC)to overcome BBB.The 6-hydroxyl group of chitosan was acylated and then attached to the targeting peptide.Their structures were characterized by nuclear magnetic resonance spectroscopy,infrared spectroscopy and UV-visible spectroscopy.The surface morphology was observed by transmission electron microscopy.And the particle sizes distribution,zeta potential,drug loading and release efficiency,biocompatibility,biological safety,passing in and out of the cells and the ability of penetrating the cells membrane were studied.The main research results were as follows:Peptide12-PEG-HC was successfully synthesized.The particle sizes was about 80 nm,and the zeta potential was 4.13 m V.The particle sizes was small and the distribution was uniform.The surface of the particle was positive charge.The drug loading was up to 17.35% and the encapsulation efficiency reached 34.7%.There was almost no side leakage of the drugs in a short time in the acidic environment with p H = 5.3.There was almost no side leakage at p H = 7.4.At the same time,the peptide has a targeted effect.These factors are essential for drug delivery.After some biological evaluation,it shows a very low cell toxicity,co cultured cell survival rate is above 80%.The Live/Dead experiment also showed that the cell viability was good and the cells could grow and multiple normally.The hemolysis index is lower than 5%,indicating good biocompatibility.It can be able to enter and exit cells through phagocytosis.Peptide12-P-PEG-HC micelles have a certain ability to penetrate the cell membrane.These datas suggest that Peptide12-PEG-HC is a potentially effective drug carrier that overcomes the blood-brain barrier and may have other biological applications.Secondly,we prepared a kind of nanocomposite micellar Diethylene-polylysine-2,3-dimethyl maleic anhydride(D-PLL-DMMA)/ Peptide12-PEG-HC as a drug carrier to overcome the dense pancreatic tumor cells.The D-PLL-DMMA was synthesized and its structure was characterized by nuclear magnetic resonance spectroscopy.D-PLL-DMMA is negatively charged and Peptide12-PEG-HC is positively charged.The two structures can be self-assembled into D-PLL-DMMA/ Peptide12-PEG-HC micelles.The particle sizes distribution and zeta potential under different synthetic conditions were studied,and the following main research results were obtained:Different grafting rates of HC and PEG-HC were synthesized.The best particle sizes and stable structure PEG-HC can be obtained when the grafting rate of HC was 1:0.02,1:0.05 or 1:1.The particle sizes were 88 nm,85nm and 150 nm,respectively.The PDI values were 0.064,0.088 and 0.246,respectively.Different concentration of D-PLL-DMMA could bring different particle sizes distribution of D-PLL-DMMA / Peptide12-PEG-HC micelles.The particle size distribution of D-PLL-DMMA solution(0.1~1 mg/m L)and Peptide12-PEG-HC(1mg/m L)self-assembled into micelles was studied.The results showed that the micelles showed a particle size of 138 nm and PDI = 0.319 when the concentration of D-PLL-DMMA was 0.6 mg / m L.in addition,its particle size is very small,and the distribution is uniform and the structure is stable.