The Preparation And Research Of Hydroxyapatite As A Novel Carrier Material Of Preliposomes

Doxorubicin,abroad-spectrumantitumordrug,hasahightherapeutic index.However,it has a strong cardiotoxicity after acting on the human body.It also produces bone marrow suppression and other adverse reactions,limits its clinical application.Liposomal preparations,as a new type of preparation,have many advantages such as targeting,good histocompatibility,long-lasting effect,reducing the toxic side effects of drugs and protecting encapsulated drugs,etc.However,liposomes are liquid preparations,and phospholipids are easily oxidatively hydrolyzed in water-soluble nights,and drugs are prone to leakage.The precursor liposomes are usually dry and well-fluid solid particles,when add aqueous solution will form liposomes.Theeaseofstorageissignificantlyimprovedliposome stability.Conventional precursor liposome carrier materials such as sorbitol,mannitol,etc.,their loading is small.It can not reach the required concentration for clinical treatment.Currently,there is a need for an efficient carrier material that can carry more phospholipids in order to form more liposomes.Hydroxyapatite?HAP?has not been reported to used as a carrier for research.It is a porous material with a very high specific surface area and strong adsorption and loading capacity.It is also a major componentofhumanteethandbones,withgoodbiocompatibilityand biodegradability.As a drug carrier is very safe and it will be a good new type of carrier material.This paper,it aims to increase the carrier loading of precursor liposomes.HAP nanoparticles were synthesized by chemical precipitation method,sol-gel method and CTAB template method.It was found that the HAP synthesized by the CTAB template method has a higher specific surface area and a uniform pore.The flow properties of synthesized hydroxyapatite powder with CTAB were investigated.The angle of repose was 33.25°C,the bulk density?_loose=0.350,the tap density?_solid=0.040,and the degree of compression=13.58%.It is extremely hygroscopic and has a moisture absorption rate of 24.09%.In this paper,the doxorubicin proliposomes were prepared by spray drying method using mannitol,lactose and HAP nanoparticles as carriers.When HAP was used as a carrier,the entrapment efficiency was high and the drug loading was2.45%.Compared with lactose and mannitol,the drug loading increased by 94%and74%respectively,and the lactose and mannitol loadings were 1.26%and 1.41%.As a carrier of the precursor liposome,HAP has obvious advantages and greatly increases the drug loading.The preparation process of the precursor liposome was investigated and optimized,and the best prescription was obtained and verified.The basic properties of the precursor liposomes and liposomes were investigated,and the stability of high temperature,high humidity,and strong light irradiation was examined.This paper established a method for the determination of doxorubicin?Dox?content using high performance liquid chromatography?HPLC?.Glucose gel method?G-50?was used to separate liposomes from free drugs,and established the methods to determine the entrapment efficiency and drug loading.Taking the entrapment efficiency and drug loading as indicators,the effect of prescription on precursor liposomes was investigated by single factor.By optimizing the prescription by orthogonal design,the best prescription for the ratio of carrier phospholipids 4:1,cholesterol phospholipids 1:5,and phospholipids ratio 1:10 was obtained,and a high entrapment efficiency of 84.1%was achieved for precursor liposomes and the liquidity is also very good.Discovered by the stability test of high temperature,high humidity and strong light irradiation.Doxorubicin proliposome particles are more hygroscopic but not sensitive to high temperatures and strong light exposure.The average particle size of the liposomes was 213.2 nm,the PDI was 0.197,and the range of the particle size distribution was also uniform.The measured Zeta potential was 17.6 mv.In vitro release studies show that it has a long term and slow release effect.In summary:Hydroxyapatite is an excellent precursor liposome carrier material,which can significantly increase the drug loading,providing a basis for its application as a novel carrier material in the market.