Experimental Study On Inhibition Of Fibrous Dysplasia By Suramin-Loaded Active Targeting Drug Delivery

ObjectiveComparative analysis of bone resorption and bone formation in fibrous dysplasia were first carried out in our study.Then active targeting drug delivery based on hyperbranched poly(amine-ester)s were synthesized and suramin sodium was loaded to interfere the bone mesenchymal stem cells of FD,aiming to know whether the drug delivery loaded suramin sodium can inhibit the abnormal bone resorption and bone formation in FD and cure FDMethod1.Scanning electron microscope were used to observe the ultrastructure in FD and OF;immunohistochemistry,real-time PCR and western blotting were used to detect the difference of bone resorption and bone formation between them.2.Novel active targeting cationic drug delivery was prepared through protontransfer polymerization of commercially available glycidyl methacrylate and triethanolamine in the presence of potassium hydride catalysis,then modified by alendronate.The structure and properties of the resulting hyperbranched poly(amine-ester)s were systematically analyzed by nuclear magnetic resonance technology,Fourier transform infrared spectroscopy,dynamic light scattering and transmission electron microscopy.MTT assay was employed to assess the biocompatibility of the copolymers.The strong affinity of the micelles to bone was confirmed by the hydroxyapatite(HA)binding assay.3.Suramin was encapsulated into the micelles and confirmed by DLS and TEM.Then MTT assay and cell growth curve were employed to detect whether the suramin-loaded micelles can inhibit the bone mesenchymal stem cells of FD.Results1.Active bone formation existed both in FD and OF but in a different way.Expression of osteoprotegerin(OPG)was higher in FD than OF(P<0.05),indicating that more active bone resorption in OF than FD.2.Novel active targeting cationic drug delivery Suc-HBPAE-ALE was successfully synthesized and verified by NMR and FTIR.The results showed that weight-average molecular weight was about 9.0*10~3g/mol,PDI was about 1.5.DLS and TEM showed that the size of micelles was about 60-70nm.The assay HA binding of Suc-HBPAE-ALE in vitro indicated the copolymer has the strong targeted capability,about 80%of the copolymer micelles have absorbed to the surface of HA crystals after incubating with HA for 20 min.MTT assay showed the drug delivery had good biocompatibility.When the concentration of copolymers is up to 1 mg/mL,the survival rate is over 80%after 48h incubation with the BMSCs.3.In vitro drug release results revealed that the suramin loaded Suc-HBPAE-ALE micelles are relatively stable under neutral conditions.Meanwhile,the results showed that the micelles displayed acid-triggered(pH=5.0)drug release behaviors,cumulative release was 62.645%within 40h.The proliferation inhibition of bone mesenchymal stem cells of FD was evaluated by MTT assay and cell growth curve.100mg/ml micelles loaded suramin could inhibit the proliferation of BMSC of FD.Conclusion1.FD and OF were different in either bone formation or bone resorption.More active bone resorption were observed in OF than FD while FD was mainly dominated by abnormal bone formation.2.The drug delivery of Suc-HBPAE-ALE had excellent active targeting and good biocompatibility.3.Suramin loaded Suc-HBPAE-ALE,taking advantage of active targeting and pH-sensitivity,released suramin into the surrounding area of FD to inhibit bone mesenchymal stem cells.Thus achieving the aim of interfere the abnormal bone resorption and formation in FD and inhibit the growth and development of FD.This novel Suramin loaded micelle provided a new way to treat FD in clinic.