Controlled Fabrication Of One-dimensional Hydroxyapatite Nanomaterials And Their Application As Drug Carriers For Proteins

Drug delivery system has the advantages of fewer times of usage,stable plasma concentration and less side effects,which can effectively treat chronic diseases.As an important part of drug delivery system,the development of drug sustained release carrier has become one of the hot spot in the field of biomaterials.As the main inorganic component of human hard tissue,hydroxyapatite?HAp?with good biocompatibility,biodegradability and non-immunogenicity has broad application prospects in the field of drug sustained release carrier.Researchers usually use morphological modifiers to prepare porous or hollow HAp nanomaterials.However,the prepared materials will inevitably remain residual additives and directly affect the interaction between HAp and human tissues,making biosecurity difficult to be guaranteed.In addition,there are some defects such as low mechanical strength,high degree of crystallization and lack of essential trace elements for the organism in artificial HAp.Therefore,it has been one of the most difficult problems in the field of controllable preparation of HAp nanomaterials with excellent biological properties,high safety,good drug loading and release properties.In this dissertation,HAp nanobelts?HNBs?,zinc-doped HAp?Zn HAp?and strontium-doped HAp?Sr HAp?nanorods were controllably prepared via a hydrothermal route without using any morphological modifiers,respectively.And the products were characterized by X-ray diffractometer,Fourier transform infrared spectroscopy,scanning electron microscope,inductively coupled plasma emission spectrometer and specific surface and pore size distribution analyzer.Then the protein adsorption and sustained release properties of bovine serum albumin?BSA?and lysozyme?LYS?were investigated onto the HNBs,Zn HAp and Sr HAp,respectively.The main research results are as follows.?1?The pure HNBs consisted of uniform nanobelts.And the chemical composition and crystal structure of HNBs were basically the same as those of the standard HAp.The products had large crystallinity and grew preferentially along the direction of?3 0 0?diffraction crystal plane.After doping,the chemical groups and crystal structures of Zn HAp and Sr HAp did not change obviously,but the morphologies changed from banded to rod-like shape.The small pores were found on the surface of products,and the specific surface area and pore volume of products increased.Meanwhile,compared with HNBs,the intensity of?3 0 0?surface peaks of Zn HAp and Sr HAp decreased and the lattice parameters changed.In addition,the characteristic diffraction peaks of Zn HAp and Sr HAp were partially broadened,and the crystallinities decreased.?2?Environmental factors such as different p H values of buffer solutions,ionic strength and concentration of PO₄^3- had different impacts on the performances of HNBs adsorbing proteins.The results showed that the adsorption capacity of BSA and LYS onto HNBs firstly increased and then decreased,and reached the maximum when the p H value of buffer solution was equal to the isoelectric point of the protein with the increase of p H.When the p H value was constant,the amount of BSA adsorbed onto HNBs increased and the amount of LYS adsorbed decreased with the increase of ionic strength.With the increase of concentration of PO₄^3-,the amounts of BSA and LYS adsorbed onto HNBs decreased.Adsorption kinetics and thermodynamics of BSA and LYS onto HNBs were researched and the results indicated that the adsorption processes all could be described by pseudo-second-order adsorption kinetics model.The former was in accordance with Langmuir isothermal adsorption model and the latter was compatible with Freundlich isothermal adsorption model.Futhermore,the adsorption was spontaneous and endothermic and the process of entropy increase.The in vitro release results showed that HNBs loaded with proteins had a sustained release effect,and the cumulative release rate of protein increased with the increase of concentration of PO₄^3-.At the same time,HNBs had the characteristics of p H response to BSA release in vitro,but not to LYS.?3?The isothermal adsorption experiments of proteins onto Zn HAp and Sr HAp found that the adsorption processes of BSA onto Zn HAp and Sr HAp conformed to Langmuir isothermal adsorption model,and the adsorption processes of LYS conformed to Freundlich isothermal adsorption model.The results of the influence of metal doping on adsorption properties showed that incorporation of Zn was not conducive to the adsorption of BSA onto Zn HAp,but helpful to the adsorption of LYS onto Zn HAp,and 1Zn HAp possessed the highest LYS loading amount of 115.1 mg/g,which was 3.786 times that of HNBs.Incorporation of Sr was conducive to the adsorptions of BSA and LYS onto Sr HAp.The 1Sr HAp possessed the highest BSA loading amount of 55.52 mg/g,which was 14.64% higher than that of HNB,and 15 Sr HAp possessed the highest LYS loading amount of 90.54 mg/g,which was 2.978 times that of HNBs.The results of in vitro release showed that the release time of Zn HAp and Sr HAp loaded with proteins could reach more than 30 h in vitro,which indicated that they had some certain sustained release effects.Moreover,compared with HNBs,incorporation of Zn could accelerate the release rate of BSA from Zn HAp in vitro,but slow down the sudden release of LYS from Zn HAp.Incorporation of Sr could slow the early burst release of BSA and LYS from Sr HAp,and Sr HAp had better sustained release performances of proteins.Meanwhile,the 1Zn HAp and 1Sr HAp had the characteristics of p H response to BSA release in vitro.But 1Zn HAp and 15 Sr HAp had no p H response to LYS release.