Preparation And Drug Delivery Property Of Fiber-based Mesoporous SiO₂ Drug Carrier

Wound dressing is a medical product that protects wounds,prevents wound infections,and promotes wound healing.With the care of general wound dressings,the structural and functional integrity of normal acute wounds will be quickly restored.However,for some patients with diabetic foot ulcers,pressure ulcers,and burns,it is difficult to heal wounds in an orderly manner.Some conditions make it difficult to heal the wounds,such as local pain,coagulation difficulties,bacterial infections,etc.Therefore,it is necessary to develop a new type of dressing to meet the different needs of different periods of wound healing.The normal wound healing process is mainly divided into four stages:hemostatic,inflammatory,proliferative,and remodeling.Wounds are susceptible to bacterial infection when they in inflammatory,which is the main reason for delayed wound healing.In order to solve the problem of long-acting antibacterial and continuous drug release in the chronic wound inflammatory phase,in this paper,multi-stage drug-loading systems such as mesoporous drug carriers,mesoporous-fiber composite drug carriers,and mesoporous-multilevel fiber composite drug carriers was designed and prepared.And the drug release properties of different drug carriers were studied and compared.In order to find the research and development purpose of precise wound dressing design that can control inflammation and accelerate wound healing in a long-term effect,the role of different drug delivery systems in wound healing were analyzed,especially before and after the inflammatory phase.The specific research content is as follows:Firstly,design and preparation of mesoporous drug carriers.Mesoporous silica nanoparticles(MSNs)were synthesized under alkaline conditions based on the sol-gel method by using Cetyltrimethylammonium bromide(CTAB)as a soft template and Ethyl orthosilicate(TEOS)as an organic silicon source.The optimal synthesis parameters were discussed by changing the pH,template concentration and stirring speed during the synthesis.The MSNs synthesized under optimal parameters have a specific surface area of 821.124 m~2/g,a pore volume of 0.646 cm~3/g,and an average mesoporous diameter of 3.537 nm.Secondly,the antibacterial drug ciprofloxacin hydrochloride(Cip)was loaded into MSNs by the ultrasonic impregnation method.The effects of drug solution concentration on drug loading and encapsulation efficiency of MSNs were discussed,and an in vitro release test was performed under acidic conditions.It was found that as the concentration of the drug solution increased,both the drug loading and the encapsulation rate of MSNs increased first and then decreased.When the Cip solution concentration was 7 mg/mL,it showed optimal drug loading performance.In vitro release results show that Cip has a good sustained release effect in the drug carrier,the release rate from fast to slow,and sustained release within 168h.Next,the aforementioned MSNs was mixed with the organic polymer material polycaprolactone(PCL).PCL/MSNs-Cip and PCL-Cur/MSNs-Cip composite fiber membranes were prepared by electrostatic spinning with curcumin(Cur)as a guest molecule in PCL.By comparing release results,it was shown that the drug release rate of Cip in the fibrous structure is much lower than the drug release rate in MSNs due to the encapsulation of the fibrous structure,the release trends of Cip in MSNs-Cip and PCL/MSNs-Cip are basically the same.While in PCL-Cur/MSNs-Cip fiber membrane,the release rate of the Cur contained in the PCL is higher than that of the Cip loaded in the MSNs.Within 12 hours,the cumulative release rates of the two drugs were 53.43%and 28.58%,respectively.A large number of antibacterial drugs were released,and the occurrence of inflammatory reactions was controlled during the wound healing process.After 24 hours,the release rate of Cur gradually slowed down,and Cip continued to release slowly,extending the overall antibacterial effect of the fiber membrane and had a long-lasting antibacterial effect.Finally,the above-mentioned dual-drug-loaded organic-inorganic composite fiber was used as the core layer,chitosan(CS)was used as the shell layer,and lidocaine hydrochloride was used as the guest molecule in the shell layer.It was found that in the early stages of wound healing,the fibrous shell analgesic drug Lid is released in large quantities,which can play a rapid analgesic effect.Cur in the middle nuclear layer was continuously released within 72h,which provided antibacterial support for wound healing,after 72h,the release curve became flat.At this time,the release of the antibacterial drug Cip loaded in the mesoporous silicon still slowly rises,achieving a long-acting antibacterial effect.It can be obtained by analyzing the release curve that all the above drug releases follow Fick's law,and diffusion is the main driving force for drug release.The results of the antibacterial experiment showed that the multi-stage drug-released carrier fiber membrane showed long-term and sustained antibacterial properties against S.aureus and E.coli.