Safety and efficacy of thalidomide in patients with transfusiondependentβ-thalassemia:a randomized clinical trial

Thalidomide inducesγ-globin expression in erythroid progenitor cells,but its efficacy on patients with transfusion-dependentβ-thalassemia(TDT)remains unclear.In this phase 2,multi-center,randomized,double-blind clinical trial,we aimed to determine the safety and efficacy of thalidomide in TDT patients.A hundred patients of 14 years or older were randomly assigned to receive placebo or thalidomide for 12 weeks,followed by an extension phase of at least 36 weeks.The primary endpoint was the change of hemoglobin(Hb)level in the patients.The secondary endpoints included the red blood cell(RBC)units transfused and adverse effects.In the placebo-controlled period,Hb concentrations in patients treated with thalidomide achieved a median elevation of 14.0(range,2.5 to 37.5)g/L,whereas Hb in patients treated with placebo did not significantly change.Within the 12 weeks,the mean RBC transfusion volume for patients treated with thalidomide and placebo was 5.4±5.0 U and 10.3±6.4 U,respectively(P<0.001).Adverse events of drowsiness,dizziness,fatigue,pyrexia,sore throat,and rash were more common with thalidomide than placebo.In the extension phase,treatment with thalidomide for 24 weeks resulted in a sustainable increase in Hb concentrations which reached 104.9±19.0 g/L,without blood transfusion.Significant increase in Hb concentration and reduction in RBC transfusions were associated with nonβ0/β0 and HBS1L-MYB(rs9399137 C/T,C/C;rs4895441 A/G,G/G)genotypes.These results demonstrated that thalidomide is effective in patients with TDT.

MULTILAYERS AND POLY(ALLYLAMINE HYDROCHLORIDE)-GRAFTPOLY(ETHYLENE GLYCOL) MODIFIED BOVINE SERUM ALBUMIN NANOPARTICLES:IMPROVED STABILITY AND pH-RESPONSIVE DRUG DELIVERY

To improve the colloidal stability of bovine serum albumin （BSA） nanoparticles （hiPs） in diverse mediums, poly（allylamine hydrochloride） （PAH）/sodium poly（4-styrene sulfonate） （PSS） multilayers and poly（allylamine hydrochloride）-graft-poly（ethylene glycol） （PAH-g-PEG） coating were coated on the surface of BSA NPs. Stabilities of the BSA NPs in diverse mediums with different surfaces were detected by dynamic light scattering （DLS）. Multilayers and PAH-g-PEG coated BSA NPs can be well dispersed in various mediums with a narrow polydispersity index （PDI）. The BSA NPs with the highest surface density of PEG show the best stability. The multilayers and PAH-g-PEG coating do not deter the pH-dependent loading and release property of BSA NPs. At pH 9, the encapsulation efficiency of doxorubicin reaches almost 99%, and the release rate at pH 5.5 is significantly higher than that at pH 7.4.