Study On PH-responsive Hollow Mesoporous Silica Drug Delivery System

With the clinical application of propranolol hydrochloride（PNH）in infantile hemangioma,it has been found that there are many adverse reactions,including bradycardia,hypotension,hypoglycemia and seizures caused by it.In addition,propranolol hydrochloride is taken orally 3 times a day,which also greatly reduces patient compliance.These adverse reactions and too frequent administration have severely hindered the clinical application of propranolol hydrochloride in infantile hemangioma.Therefore,changing the delivery method of propranolol hydrochloride,the bioavailability and therapeutic effect of the drug may be improved.The dosage of the drug and the number of administrations can be reduced and the compliance of the patient is improved so that the safety of drug usage can be increased.The preparation and application of nano-medicine sustained and controlled-release delivery systems based on organic and inorganic materials have gradually become the focus of research.Hollow mesoporous silica spheres（HMSS）have an internal hollow structure,which can significantly improve the pharmacokinetics and pharmacodynamic properties when used as a drug sustained and controlled release carrier.In this paper,the preparation conditions of HMSS were explored.Propranolol hydrochloride was loaded in HMSS and wrapped with polydopamine（PDA）to prepare a pH-responsive hollow mesoporous silica drug delivery system.The drug release performance of the system was explored.（1）The solid silica spheres（sSiO₂）were prepared by the St（?）ber method,and the self-template method was used to prepare two kinds of HMSS with different pore structures through cationic surfactants（CTAB）assisted selective etching,respectively,wormhole-like pore structure hollow mesopores silica spheres（HMSS-W）and hollow mesoporous silica spheres with oriented pore structure hollow mesoporous silica spheres（HMSS-O）.PNH-loaded hollow mesoporous silica composite particles（HMSS-W@PNH,HMSS-O@PNH）by loading propranolol hydrochloride was prepared.The pH-responsive hollow mesoporous silica drug delivery system（HMSS-W@PNH@PDA,HMSS-O@PNH@PDA）was obtained by wrapping with PDA.The structure and performance of the delivery system was characterized by Transmission Electron Microscopy（TEM）,N₂ adsorption and desorption,Scanning Electron Microscopy（SEM）,Infrared Rpectroscopy（IR）,X-ray diffraction（XRD）and other technologies.（2）The influence of ammonia concentration on its particle size during the synthesis of s Si O₂,stirring speed on its structure during the synthesis of HMSS-W,and the amount of CTAB on its structure during the synthesis of HMSS-O were investigated.The results showed that under certain other conditions,as the concentration of ammonia decreases,that is,the amount of ammonia decreased,the average particle size of the synthesized s Si O₂ also decreased.It is the appropriate condition when 2m L ammonia water was used.The average particle size of the prepared s Si O₂ was 120nm,good monodispersity and no agglomeration with regular spherical morphology.When the stirring speed was 1000rmp/min during the synthesis of HMSS-W,the prepared HMSS-W had a good internal hollow structure,with an average particle size of 150nm and a specific surface area of710.44 m²/g.As the amount of CTAB was 750mg during the synthesis of HMSS-O,the prepared HMSS-O had a good internal hollow structure,with an average particle size of190nm and a specific surface area of 1128.66 m²/g.（3）The effects of different loading methods,different solvents,and different PNH solution concentrations on the drug loading of the system were investigated.The results showed that the appropriate drug loading conditions were dry dipping,methanol as the solvent,and the PNH solution solubility was 43 mg/m L,the drug loading capacity of HMSS-W@PNH was 42.80%,and the drug loading capacity of HMSS-O@PNH was43.79%.（4）The system’s drug release performance studies showed that the two prepared HMSS@PNH realized the sustained release of the drug,with the apparent effect;The package of PDA had a significant impact on the drug release performance of the delivery system.The cumulative drug release rate of HMSS@PNH without PDA packaging at different pH was about the same,with sustained release effect.After packaging PDA,with the decrease of pH,the cumulative drug release rate of HMSS@PNH@PDA gradually increased to achieve pH responsiveness and controlled release of drugs.The release process conformed to the Weibull model.The silicon oxide drug delivery system prepared by the pH-responsive hollow mesoporous II had practical application and promotion value.