The development of functional materials for osteoporosis is ultimately required for bone remodeling.However,grafts were accompanied by increasing pro-inflammatory cytokines that impaired bone formation.In this work,na...The development of functional materials for osteoporosis is ultimately required for bone remodeling.However,grafts were accompanied by increasing pro-inflammatory cytokines that impaired bone formation.In this work,nano-hydroxyapatite(n-HA)/resveratrol(Res)/chitosan(CS)composite microspheres were designed to create a beneficial microenvironment and help improve the osteogenesis by local sustained release of Res.Study of in vitro release confirmed the feasibility of n-HA/Res/CS microspheres for controlled Res release.Notably,microspheres had anti-inflammatory activity evidenced by the decreased expression of pro-inflammatory cytokines TNF-α,IL-1βand iNOS in RAW264.7 cells in a dose dependent manner.Further,enhanced adhesion and proliferation of BMSCs seeded onto microspheres demonstrated that composite microspheres were conducive to cell growth.The ability to enhance osteo-differentiation was supported by up-regulation of Runx2,ALP,Col-1 and OCN,and substantial mineralization in osteogenic medium.When implanted into bone defects in the osteoporotic rat femoral condyles,enhanced entochondrostosis and bone regeneration suggested that the n-HA/Res/CS composite microspheres were more favorable for impaired fracture healing.The results indicated that optimized n-HA/Res/CS composite microspheres could serve as promising multifunctional fillers for osteoporotic bone defect/fracture treatment.展开更多
Novel ethyl cellulose/chitosan microspheres （ECCMs） were prepared by the method of w/o/w emulsion and solvent evaporation. The microspheres were spherical, adhesive, and aggregated loosely with a size not bigger tha...Novel ethyl cellulose/chitosan microspheres （ECCMs） were prepared by the method of w/o/w emulsion and solvent evaporation. The microspheres were spherical, adhesive, and aggregated loosely with a size not bigger than 5 pm. The drug loading efficiency of berberine hydrochloride （BH） loaded in microspheres were affected by chitosan （CS） concentration, EC concentration and the volume ratio of V（CS）/V（EC）. ECCMs prepared had sustained release efficiency on BH which was changed with different preparation parameters. In addition, the pH value of release media had obvious effect on the release character of ECCMs. The release rate of BH from sample B was only a little more than 30% in diluted hydrochloric acid （dHCl） and that was almost 90% in PBS during 24 h. Furthermore, the drug release data were fitted to different kinetic models to analyze the release kinetics and the mechanism from the microspheres. The released results of BH indicated that ECCMs exhibited non-Fickian diffusion mechanism in dHCI and diffusion-controlled drug release based on Fickian diffusion in PBS. So the ECCMs might be an ideal sustained release system especially in dHCl and the drug release was governed by both diffusion of the drug and dissolution of the polymeric network.展开更多
Chitosan/α,β-glycerophosphate （CS/α,β-GP） thermo-sensitive hydrogels presented flowable solution state at low temperature and semisolid hydrogel when the ambient temperature increased. In this research, differen...Chitosan/α,β-glycerophosphate （CS/α,β-GP） thermo-sensitive hydrogels presented flowable solution state at low temperature and semisolid hydrogel when the ambient temperature increased. In this research, different concentrations of metronida- zole encapsulated, CS and α,β-GP, as well as different acid solvents, were chosen to evaluate their influences on the drug release behaviors from CS/α,β-GP hydrogels. It was found that there was a sustaining release during the first 3 h followed by a plateau. SEM images showed that drugs were located both on the surface and in the interior of hydrogels. The optimal preparation conditions of this hydrogel for drug release were as follows： 1.8% （w/v） CS in HAc solvent, 5.6% （w/v） a, 13-GP and 5g/L metronidazole encapsulation. Cytotoxicity evaluation found no toxic effect. In order to control the release rate, 2.5 g/L chitosan microspheres with spherical shape and smooth surface were incorporated, and it was found that the initial release process was alleviated, while drug concentration had no obvious effect on the release rate. It could be concluded that the metronidzole release behaviors could be optimized according to practical applica- tions.展开更多
基金supported by the National Natural Science Foundation of China(81460173/81860326/81960268)the Department of Science and Technology of Yunnan Province of China(2017FF117(-062)/2018FE001(-137)/2018FE001(-125)/2019ZF011-2).
文摘The development of functional materials for osteoporosis is ultimately required for bone remodeling.However,grafts were accompanied by increasing pro-inflammatory cytokines that impaired bone formation.In this work,nano-hydroxyapatite(n-HA)/resveratrol(Res)/chitosan(CS)composite microspheres were designed to create a beneficial microenvironment and help improve the osteogenesis by local sustained release of Res.Study of in vitro release confirmed the feasibility of n-HA/Res/CS microspheres for controlled Res release.Notably,microspheres had anti-inflammatory activity evidenced by the decreased expression of pro-inflammatory cytokines TNF-α,IL-1βand iNOS in RAW264.7 cells in a dose dependent manner.Further,enhanced adhesion and proliferation of BMSCs seeded onto microspheres demonstrated that composite microspheres were conducive to cell growth.The ability to enhance osteo-differentiation was supported by up-regulation of Runx2,ALP,Col-1 and OCN,and substantial mineralization in osteogenic medium.When implanted into bone defects in the osteoporotic rat femoral condyles,enhanced entochondrostosis and bone regeneration suggested that the n-HA/Res/CS composite microspheres were more favorable for impaired fracture healing.The results indicated that optimized n-HA/Res/CS composite microspheres could serve as promising multifunctional fillers for osteoporotic bone defect/fracture treatment.
基金The authors are indebted to the financial support from the National Natural Science Foundation of China （Grant No. 51103035）.
文摘Novel ethyl cellulose/chitosan microspheres （ECCMs） were prepared by the method of w/o/w emulsion and solvent evaporation. The microspheres were spherical, adhesive, and aggregated loosely with a size not bigger than 5 pm. The drug loading efficiency of berberine hydrochloride （BH） loaded in microspheres were affected by chitosan （CS） concentration, EC concentration and the volume ratio of V（CS）/V（EC）. ECCMs prepared had sustained release efficiency on BH which was changed with different preparation parameters. In addition, the pH value of release media had obvious effect on the release character of ECCMs. The release rate of BH from sample B was only a little more than 30% in diluted hydrochloric acid （dHCl） and that was almost 90% in PBS during 24 h. Furthermore, the drug release data were fitted to different kinetic models to analyze the release kinetics and the mechanism from the microspheres. The released results of BH indicated that ECCMs exhibited non-Fickian diffusion mechanism in dHCI and diffusion-controlled drug release based on Fickian diffusion in PBS. So the ECCMs might be an ideal sustained release system especially in dHCl and the drug release was governed by both diffusion of the drug and dissolution of the polymeric network.
文摘Chitosan/α,β-glycerophosphate （CS/α,β-GP） thermo-sensitive hydrogels presented flowable solution state at low temperature and semisolid hydrogel when the ambient temperature increased. In this research, different concentrations of metronida- zole encapsulated, CS and α,β-GP, as well as different acid solvents, were chosen to evaluate their influences on the drug release behaviors from CS/α,β-GP hydrogels. It was found that there was a sustaining release during the first 3 h followed by a plateau. SEM images showed that drugs were located both on the surface and in the interior of hydrogels. The optimal preparation conditions of this hydrogel for drug release were as follows： 1.8% （w/v） CS in HAc solvent, 5.6% （w/v） a, 13-GP and 5g/L metronidazole encapsulation. Cytotoxicity evaluation found no toxic effect. In order to control the release rate, 2.5 g/L chitosan microspheres with spherical shape and smooth surface were incorporated, and it was found that the initial release process was alleviated, while drug concentration had no obvious effect on the release rate. It could be concluded that the metronidzole release behaviors could be optimized according to practical applica- tions.
