Evolocumab loaded Bio-Liposomes for efficient atherosclerosis therapy.

PCSK9, which is closely related to atherosclerosis, is significantly expressed in vascular smooth muscle cells (VSMCs). Moreover, Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) mediated phenotypic transformation, abnormal proliferation, and migration of VSMCs play key roles in accelerating atherosclerosis. In this study, by utilizing the significant advantages of nano-materials, a biomimetic nanoliposome loading with Evolocumab (Evol), a PCSK9 inhibitor, was designed to alleviate atherosclerosis. In vitro results showed that (Lipo + M)@E NPs up-regulated the levels of α-SMA and Vimentin, while inhibiting the expression of OPN, which finally result in the inhibition of the phenotypic transition, excessive proliferation, and migration of VSMCs. In addition, the long circulation, excellent targeting, and accumulation performance of (Lipo + M)@E NPs significantly decreased the expression of PCSK9 in serum and VSMCs within the plaque of ApoE-/- mice.

Insights into graphene oxide/ferrihydrite adsorption as pretreatment during ultrafiltration: Membrane fouling mitigation and disinfection by-product control.

In this study, a novel adsorbent of graphene oxide (GO) incorporated ferrihydrite (FH) was fabricated and integrated with ultrafiltration (UF) to remove natural organic matter (NOM), the crucial cause of membrane fouling and major precursor of disinfection by-products (DBPs). Compared with FH and powdered activated carbon (PAC), GO/FH exhibited superior removal for high molecular weight (HMW) humic- and fulvic-like substances and low molecular weight (LMW) protein. The cake layer formed by GO/FH alleviated the deposition of NOM on membrane surface or inside membrane pores. Therefore, GO/FH reduced 89% and 95% total fouling resistance and irreversible membrane resistance, respectively, together with the lowest increment of transmembrane pressure. Pearson correlation analysis indicated that DOC, rather than specific ultraviolet absorbance (SUVA) and UV254, was significantly correlated to the formation of trihalomethanes (THMs) and haloacetic acids (HAAs) when SUVA was below 4 L/mg-C.m. Whilst the HMW NOM (1-20 kDa) was highly related to dibromochloromethane (DBCM) (r = 0.98-1), the LMW fraction (< 1 kDa) was correlated with dibromochloromethane (TCAA) and dichloroacetic acid (DCAA) (r = 0.88-0.98). Inspiringly, GO/FH-UF reduced 90% of carbonaceous DBPs, the concentrations of which well met the WHO Guidelines. In summary, GO/FH-UF substantially alleviated membrane fouling and dramatically reduced DBP formation potential.