[Objective] To evaluate the cellular biocompatibility of the nano poly(L-lactic acid)-block-poly(?-caprolactone)(Nano-PLLA-b-PCL)with canine articular cells and its feasibility as a scaffold for the cartilage tissue engineering.[Methods]Nano-PLLA-b-PCL was made by liquid-liquid phase separation.Canine articular cells were isolated and multiplied in vitro.The passage 3 cells were seeded onto the PLLA-b-PCL films and cultured in the 2-dimensional environment.The cytotoxicity was measured with MTT assay.Cellular Morphological changes were observed by phase-contrast microscopy and Hoechst33342 fluorometric method.Another passage 3 cells were seeded onto the Nano-PLLA-b-PCL scaffolds(experiment group),PLLA-b-PCL scaffolds(control group)and cultured in the 3-dimensional environment for 3 weeks.The ratio of cell adhesion was detected by cell counting method.The morphological changes of cells were observed by scanning electron microscopy.The protein content in seeded cells were determined by bioinchoninic acid assay(BCA).The content of DNA was quantified using Hoechst33258 assay.[Results]MTT assay showed the PLLA-b-PCL had no cytotoxicity.The seeded cells adhered and proliferated well into the Nano-PLLA-b-PCL scaffolds,and they maintained good cell phenotype.After 21-day cell culture within the Nano-PLLA-b-PCL scaffolds,the chondrocyte DNA and protein contents increased with time.Moreover,the content of DNA and protein was higher in the experiment group than that in the control group,respectively(P

Background::Ainuovirine (ANV) is a new generation of non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus (HIV) type 1 infection. This study aimed to evaluate the population pharmacokinetic (PopPK) profile and exposure-response relationship of ANV among people living with HIV.Methods::Plasma concentration-time data from phase 1 and phase 3 clinical trials of ANV were pooled for developing the PopPK model. Exposure estimates obtained from the final model were used in exposure-response analysis for virologic responses and safety responses.Results::ANV exhibited a nonlinear pharmacokinetic profile, which was best described by a two-compartment model with first-order elimination. There were no significant covariates correlated to the pharmacokinetic parameters of ANV. The PopPK parameter estimate (relative standard error [%]) for clearance adjusted for bioavailability (CL/F) was 6.46 (15.00) L/h, and the clearance of ANV increased after multiple doses. The exposure-response model revealed no significant correlation between the virologic response (HIV-RNA <50 copies/mL) at 48 weeks and the exposure, but the incidence of adverse events increased with the increasing exposure ( P value of steady-state trough concentration and area under the steady-state curve were 0.0177 and 0.0141, respectively). Conclusions::Our PopPK model supported ANV 150 mg once daily as the recommended dose for people living with HIV, requiring no dose adjustment for the studied factors. Optimization of ANV dose may be warranted in clinical practice due to an increasing trend in adverse reactions with increasing exposure.Trial registration::Chinese Clinical Trial Registry https://www.chictr.org.cn (Nos. ChiCTR1800018022 and ChiCTR1800019041).