BACKGROUND:Titanium alloys lack biological activity when used as orthopedic implants,which can lead to implant loosening and periprosthetic infection.Therefore,it is of great significance to study a titanium alloy surface modification method that combines osteogenic and anti-infection functions.OBJECTIVE:To study the physical and chemical properties of titanium alloy modified with copper and strontium binary doped calcium silicate composite coating,and to evaluate its bone-promoting and antibacterial potential.METHODS:Ball milling and granulation methods were used to prepare composite powder containing copper oxide(CuO),strontium oxide(SrO),and calcium silicate(CS).A copper-strontium binary doped calcium silicate composite coating was prepared on the surface of titanium alloy(Ti6Al4V)through atmospheric plasma spraying technology.The composite coating was characterized.The titanium alloy extract,calcium silicate coating modified titanium alloy extract,copper-doped calcium silicate composite coating modified titanium alloy extract,and copper-strontium binary doped calcium silicate composite coating modified titanium alloy extract were co-cultured with MC3T3-E1 cells to detect the biosafety and osteogenic properties of the materials.Staphylococcus aureus(or Escherichia coli)were co-cultured with titanium alloy,calcium silicate coating modified titanium alloy,copper-doped calcium silicate composite coating modified titanium alloy,and copper-strontium binary doped calcium silicate composite coating modified titanium alloy.The in vitro antibacterial properties of the materials were detected by scanning electron microscopy and plate counting method.RESULTS AND CONCLUSION:(1)Scanning electron microscopy showed that a large number of nanostructures existed on the rough surface of the copper-strontium binary doped calcium silicate composite coating.The composite coating was successfully sprayed on the surface of titanium alloy.The composite coating could slowly release Sr2+and Cu2+in vitro.The release concentration of Sr2+was greater than that of Cu2+.(2)CCK-8 assay and cell live/dead staining results showed that the copper-doped calcium silicate composite coating modified titanium alloy had certain cytotoxicity.The calcium silicate coating and the copper-strontium binary doped calcium silicate composite coating modified titanium alloy had good biocompatibility.Alkaline phosphatase and alizarin red staining results showed that compared with titanium alloy and calcium silicate coating modified titanium alloy,copper strontium binary doped calcium silicate composite coating modified titanium alloy showed better osteogenic properties.(3)The results of scanning electron microscopy,bacterial coating,and bacterial counting method showed that compared with titanium alloy and calcium silicate coating modified titanium alloy,copper-doped calcium silicate composite coating and copper strontium binary doped calcium silicate composite coating modified titanium alloy can effectively inhibit the growth of Staphylococcus aureus and Escherichia coli,showing antibacterial potential.(4)The results indicate that copper strontium binary doped calcium silicate composite coating modified titanium sheet has good biocompatibility,osteogenic and antibacterial properties.

BACKGROUND:Titanium alloys lack biological activity when used as orthopedic implants,which can lead to implant loosening and periprosthetic infection.Therefore,it is of great significance to study a titanium alloy surface modification method that combines osteogenic and anti-infection functions.OBJECTIVE:To study the physical and chemical properties of titanium alloy modified with copper and strontium binary doped calcium silicate composite coating,and to evaluate its bone-promoting and antibacterial potential.METHODS:Ball milling and granulation methods were used to prepare composite powder containing copper oxide(CuO),strontium oxide(SrO),and calcium silicate(CS).A copper-strontium binary doped calcium silicate composite coating was prepared on the surface of titanium alloy(Ti6Al4V)through atmospheric plasma spraying technology.The composite coating was characterized.The titanium alloy extract,calcium silicate coating modified titanium alloy extract,copper-doped calcium silicate composite coating modified titanium alloy extract,and copper-strontium binary doped calcium silicate composite coating modified titanium alloy extract were co-cultured with MC3T3-E1 cells to detect the biosafety and osteogenic properties of the materials.Staphylococcus aureus(or Escherichia coli)were co-cultured with titanium alloy,calcium silicate coating modified titanium alloy,copper-doped calcium silicate composite coating modified titanium alloy,and copper-strontium binary doped calcium silicate composite coating modified titanium alloy.The in vitro antibacterial properties of the materials were detected by scanning electron microscopy and plate counting method.RESULTS AND CONCLUSION:(1)Scanning electron microscopy showed that a large number of nanostructures existed on the rough surface of the copper-strontium binary doped calcium silicate composite coating.The composite coating was successfully sprayed on the surface of titanium alloy.The composite coating could slowly release Sr2+and Cu2+in vitro.The release concentration of Sr2+was greater than that of Cu2+.(2)CCK-8 assay and cell live/dead staining results showed that the copper-doped calcium silicate composite coating modified titanium alloy had certain cytotoxicity.The calcium silicate coating and the copper-strontium binary doped calcium silicate composite coating modified titanium alloy had good biocompatibility.Alkaline phosphatase and alizarin red staining results showed that compared with titanium alloy and calcium silicate coating modified titanium alloy,copper strontium binary doped calcium silicate composite coating modified titanium alloy showed better osteogenic properties.(3)The results of scanning electron microscopy,bacterial coating,and bacterial counting method showed that compared with titanium alloy and calcium silicate coating modified titanium alloy,copper-doped calcium silicate composite coating and copper strontium binary doped calcium silicate composite coating modified titanium alloy can effectively inhibit the growth of Staphylococcus aureus and Escherichia coli,showing antibacterial potential.(4)The results indicate that copper strontium binary doped calcium silicate composite coating modified titanium sheet has good biocompatibility,osteogenic and antibacterial properties.

To prepare and optimize the self-microemulsion co-loaded with tenuifolin and β-asarone(TF/ASA-SMEDDS) and evaluate its quality. The prescription compositions of TF/ASA-SMEDDS were screened by solubility test, single factor test and pseudo-tern-ary phase diagram, and the prescriptions were further optimized by Box-Behnken response surface method, with the drug loading and particle size as the evaluation indexes. Then the optimized TF/ASA-SMEDDS was evaluated for emulsified appearance, particle size, morphology and drug release in vitro. The optimized prescription for TF/ASA-SMEDDS was as follows: caprylic citrate triglyceride polyoxyethylene castor oil-glycerol(10.8∶39.2∶50), drug loading of(5.563±0.065) mg·g~(-1) for tenuifolin and(5.526±0.022) mg·g~(-1) for β-asarone; uniform and transparent pan-blue nanoemulsion can be formed after emulsification, with particle size of(28.84±0.44) nm. TEM showed that TF/ASA-SMEDDS can form spherical droplets with a uniform particle size after emulsification; In vitro release test results showed that the drug release rate and cumulative release of tenuifolin and β-asarone were significantly improved. The preparation process of TF/ASA-SMEDDS was simple and can effectively improve in vitro release of tenuifolin and β-asarone.
Anisoles ; Biological Availability ; Diterpenes, Kaurane ; Drug Delivery Systems ; Emulsions ; Particle Size ; Solubility ; Surface-Active Agents

Herpetospermum caudigerum lignans (HTL), one of the potential drugs with anti-hepatitis B virus and hepatoprotective effects, has limited clinical applications because of poor aqueous solubility and low bioavailability. Both herpetrione (HPE) and herpetin (HPN) are the most abundant ingredients in HTL and exhibit weak acidity. The purpose of the present study was to produce dried preparations of HTL (composed of HPE and HPN) nanosuspensions (HTL-NS) with high redispersibility using lyophilization technology. The HTL-NS was prepared by utilizing precipitation-combined homogenization technology based on acid-base neutralization reactions, and critical formulation and process parameters affecting the characteristics of HTL-NS were optimized. The resultant products were characterized by particle size analysis, SEM, XRD, stability, solubility, dissolution and in vivo bioavailability. HTL-NS showed near-spherical-shaped morphology and the size was 243 nm with a narrow PDI value of 0.187. The dried preparations with a relatively large particle size of 286 nm and a PDI of 0.215 were achieved by using 4% (W/V) mannitol as cryoprotectants, and had a better stability at 4 or 25 °C for 2 months, compared to HTL-NS. In the in vitro test, the dried preparations showed markedly increased solubility and dissolution velocity. Besides, in the in vivo evaluation, it exhibited significant increases in AUC, CMRT and a decrease in T, compared to the raw drug. In conclusion, our results provide a basis for the development of a drug delivery system for poorly water-soluble ingredients with pH-dependent solubility.
Animals ; Biological Availability ; Cell Line ; Chemistry, Pharmaceutical ; methods ; Drug Carriers ; chemistry ; Drug Delivery Systems ; Humans ; Lignans ; administration & dosage ; chemistry ; pharmacokinetics ; Male ; Nanoparticles ; administration & dosage ; chemistry ; Particle Size ; Rats ; Rats, Wistar ; Solubility ; X-Ray Diffraction

BACKGROUND:The mechanism underlying Wal erian degeneration fol owing peripheral nerve injury is complex. Immune regulation on Wal erian degeneration is beneficial for early repair of perpheral nerve injury.
OBJECTIVE:To investigate the effects of Tol-like receptor 4 (TLR4) antagonist on Wal erian degeneration and axonal regeneration after early peripheral nerve injury in rats.
METHODS:Fifty male Wistar rats were recruited and randomly divided into treatment group (n=20), model group (n=20) and sham group (n=10). The right sciatic nerves of rats in treatment and model groups were cut and sutured end-to-end, while the sciatic nerves of rats in sham group were only exposed. In the treatment group rats were intravenously injected with 0.15 mg/kg TAK-242 via tail vein 1 hour preoperatively and 7 days postoperatively, and the rats in the other two groups were given intravenous injection of the same volume of normal saline. The sciatic nerves were removed at 24 hours, 3, 4 and 7 days after surgery.
RESULTS AND CONCLUSION:Real-time PCR indicated that the mRNA expressions of interleukin-1βand monocyte chemoattractant-1 were significantly increased in the model group compared with the sham group at 24 hours after surgery (both P<0.001), while the expressions were significantly decreased after TAK-242 injection (both P<0.001). Immunofluorescence showed that compared with the model group, down-regulated expression of CD68+and iba1+cel s appeared in the treatment group at 3 days after surgery (P<0.01, P<0.05). Luxol fast blue staining revealed that demyelination at the sciatic nerve stump appeared in both model and treatment groups at postoperative 7 days, but myelin debris clearance in the treatment group was significantly reduced compared with the model group (P<0.05). Hematoxylin-eosin staining showed that a lot of inflammatory cel s, Schwann cells and regenerated nerve fibers at the sciatic nerve stump were found in the model group, while there were few inflammatory cells, Schwann cel s and regenerated nerve fibers in the treatment group at 7 days after surgery. Immunohistochemistry found that the expression of growth-associated protein-43 in the treatment group was significantly lower than that in the model group at 4 days postoperatively (P<0.05). Besides, compared with the model group, a significantly decreased sciatic functional index was found in the treatment group at 20, 30 and 40 days after surgery (P<0.05). These results show that TLR4 antagonists delay early nerve regeneration in rats after sciatic nerve injury probably by inhibiting the TLR4 signaling pathway.