nevirapine (nevirapine ER / nevirapine XR / nevirapine, XR)

mPEG-b-PCL-Based Nanoformulations of Aziridine-Functionalized 1,3,5-Triazine Derivative for Cancer Treatment.

Bagaeva Irina I, Sinitsyna Ekaterina E, Zmitrichenko Yuliia Y, Tochilnikov Gregorii G et al.

Developing nanoformulations of antitumor drugs represents a critical priority in addressing key challenges of free drug administration such as low therapeutic efficacy, poor bioavailability, and severe side effects, including high systemic toxicity. In this study, mPEG-b-PCL block copolymers of different molecular weights were synthesized and applied to develop nanoformulations of the antitumor aziridine-functionalized 1,3,5-triazine derivative, dioxadet (DOD) via nanoprecipitation. The resulting DOD-loaded nanoparticles exhibited optimal characteristics for intravenous administration, and high encapsulation efficiency. The effect of mPEG-b-PCL molecular weight on drug encapsulation and release was investigated, and the results were elucidated through computational analysis of the molecular binding mechanism between DOD and PCL. Release profiles showed a sustained biphasic pattern. Determination of DOD concentration in blood of healthy rats indicated that the nanoformulation extended DOD's circulation time. The empty nanoparticles were well-tolerated by both normal and cancer cells. The nanoformulation maintained inhibitory activity against A549 cells with an IC50, comparable to that of free DOD. The antitumor efficacy and reduced toxicity of the optimized nanoformulation were demonstrated in mice using two ascitic tumor models (Ehrlich ascites carcinoma and L1210 lymphoid leukemia) and one solid tumor model (Lewis lung epidermoid carcinoma) with the greatest therapeutic effect observed against the solid tumor.

Factors Associated With Recurrent Venous Thromboembolism During Extended Apixaban Therapy for Cancer-Associated Thrombosis.

Mahé Isabelle I, Chidiac Jean J, Righini Marc M, Le Gal Grégoire G et al.

Structure-Barrier-Release Relationships of Low-Temperature ALD ZrO2 Thin Films on Co-Cr Alloys: Reducing Long-Term Co and Cr Ion Release in Artificial Saliva.

Ziębowicz Anna A, Groelich Wiktoria W, Kajzer Anita A, Kajzer Wojciech W et al.

Co-Cr alloys are widely used in biomedical devices owing to their excellent mechanical properties and corrosion resistance; however, sustained metal-ion release in physiological environments remains an important materials concern. Low-temperature atomic layer deposition (ALD) enables the formation of conformal ceramic barriers that can restrict long-term metal-ion transport. In this study, nominally ~50 nm ALD-derived ZrO2 coatings were deposited on Co-Cr substrates manufactured by investment casting (CAST), CAD/CAM milling (MILLED), and laser powder bed fusion (PRINTED). The coatings were characterized using scanning electron microscopy (SEM), atomic force microscopy (AFM), Raman spectroscopy, transmission electron microscopy with selected-area electron diffraction (TEM/SAED), and X-ray photoelectron spectroscopy (XPS), while the electrochemical response was evaluated by open-circuit potential (OCP) and electrochemical impedance spectroscopy (EIS). Long-term barrier performance was quantified by inductively coupled plasma atomic emission spectroscopy (ICP-AES) as cumulative Co and Cr release for all manufacturing routes and Mo release for the Mo-containing CAST and PRINTED alloys after 28 days in artificial saliva at 37 °C. ZrO2 deposition reduced cumulative Co and Cr release for all manufacturing routes. Mo release was also reduced in the Mo-containing alloys, with Mo remaining below the analytical detection limit (<0.005 µg cm-2) for the PRINTED + ZrO2 system. Electrochemical measurements further demonstrated manufacturing-route-dependent differences in barrier response between the initial and 28-day exposure states. Overall, the findings establish a structure-barrier-release framework linking coating formation and electrochemical response with cumulative ion release, and identify 28-day cumulative ion release as a practical functional descriptor for comparing the long-term performance of ALD-derived ceramic barriers on Co-Cr alloys.

Bismuth-Triggered Copper Release From CuS Nanosheets Enables Synergistic Ion-Interference and Chemodynamic/Photothermal Therapy.

Su Ziwei Z, Xu Hongkang H, Su Zhuping Z, Sheng Kangliang K et al.

Despite the promising potential of Cu-based nanozymes in cancer therapy, the therapeutic efficacy remains limited by the difficulty of achieving controlled Cu-ion release without compromising lattice integrity and catalytic activity. Herein, we developed a therapeutic nanoplatform utilizing bismuth (Bi)-doping techniques to control the release of copper (Cu) ions, enabling synergistic ion interference therapy, chemodynamic therapy (CDT) and photothermal therapy (PTT) for tumor treatment. Based on the instability of Bi-based compounds in the tumor microenvironment (TME), Bi ions are preferentially released from Bi-doped CuS nanosheets (Bi-CuS NSs), exposing more Cu vacancies and facilitating Cu ion release compared to CuS NSs. More importantly, upon cellular internalization, the released copper ions induce ionic homeostasis disruption, leading to cuproptosis in liver cancer cells. Simultaneously, the Cu vacancies generated by ion release enhance the peroxidase-like activity to produce more reactive oxygen species and improve the photothermal conversion efficiency to induce localized hyperthermia, synergistically amplifying tumor cell destruction. Consequently, Bi-CuS NSs exhibit excellent potential for synergistic metal ion interference and photothermal/chemodynamic therapy, enabling the multimodal treatment of hepatocellular carcinoma. This study presents a Bi-mediated strategy for regulating Cu-ion release and catalytic activity in metal-based cancer nanomedicines.