pirfenidone (KitosCell LP)

Dual Delivery from a Multilayer Buccal Film: Rational Design of a Combination Product for Localized Treatment of Oral Fibrosis.

Raggi Veronica V, Gelli Rita R, Salar Neslihan D ND, Widak Assumpta A et al.

Oral submucous fibrosis (OSF) is a chronic, progressive, and potentially malignant disorder characterized by severe oral cavity remodeling. The condition is driven by a painful burning sensation and a pathognomonic restriction of mouth opening (trismus), severely diminishing patients' quality of life. Current clinical management represents a critical bottleneck in patient care, as conventional strategies rely heavily on painful intralesional injections or systemic regimens plagued by localized toxicity and poor compliance. Consequently, there is an urgent demand for localized, noninvasive, and patient-compliant delivery systems capable of sustaining therapeutic drug levels directly at the fibrotic site. To address this challenge, we developed, optimized, and characterized a multilayered buccal film ("sandwich" architecture) combining bupivacaine (Bupi) and pirfenidone (PFD) to achieve an immediate anesthetic effect followed by sustained antifibrotic action. A Design of Experiments (DoE) approach optimized both formulation composition and the critical process parameter (drying rate), yielding a fast-dissolving (FD) layer engineered for rapid Bupi release alongside a slow-dissolving (SD) layer tailored for prolonged PFD dissolution. The resulting monolithic system successfully immobilizes both therapeutics in a stable amorphous state, leveraging macromolecular free volume and modulated surface microtopography to regulate biphasic release kinetics. This work demonstrates the feasibility of engineering kinetically distinct, multilayered buccal films through rational design, providing a translationally viable therapeutic platform for localized management of oral fibrosis.

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.