Controlled Delivery of Corticosteroids Using Tunable Tough Adhesives.

Hydrogel-based drug delivery systems typically aim to release drugs locally to tissue in an extended manner. Tissue adhesive alginate-polyacrylamide tough hydrogels are recently demonstrated to serve as an extended-release system for the corticosteroid triamcinolone acetonide. Here, the stimuli-responsive controlled release of triamcinolone acetonide from the alginate-polyacrylamide tough hydrogel drug delivery systems (TADDS) and evolving new approaches to combine alginate-polyacrylamide tough hydrogel with drug-loaded nano and microparticles, generating composite TADDS is described.

Enhanced tendon healing by a tough hydrogel with an adhesive side and high drug-loading capacity.

Hydrogels that provide mechanical support and sustainably release therapeutics have been used to treat tendon injuries. However, most hydrogels are insufficiently tough, release drugs in bursts, and require cell infiltration or suturing to integrate with surrounding tissue. Here we report that a hydrogel serving as a high-capacity drug depot and combining a dissipative tough matrix on one side and a chitosan adhesive surface on the other side supports tendon gliding and strong adhesion (larger than 1,000 J m) to tendon on opposite surfaces of the hydrogel, as we show with porcine and human tendon preparations during cyclic-friction loadings.

Biophysical model to predict lung delivery from a dual bronchodilator dry-powder inhaler.

A biophysical lung model was designed to predict inhaled drug deposition in patients with obstructive airway disease, and quantitatively investigate sources of deposition variability. Different mouth-throat anatomies at varying simulated inhalation flows were used to calculate the lung dose of indacaterol/glycopyrronium [IND/GLY] 110/50 µg (QVA149) from the dry-powder inhaler Breezhaler. Sources of variability in lung dose were studied using computational fluid dynamics, supported by aerosol particle sizing measurements, particle image velocimetry and computed tomography.

Tough Composite Hydrogels with High Loading and Local Release of Biological Drugs.

Hydrogels are under active development for controlled drug delivery, but their clinical translation is limited by low drug loading capacity, deficiencies in mechanical toughness and storage stability, and poor control over the drug release that often results in burst release and short release duration. This work reports a design of composite clay hydrogels, which simultaneously achieve a spectrum of mechanical, storage, and drug loading/releasing properties to address the critical needs from translational perspectives. The clay nanoparticles provide large surface areas to adsorb biological drugs, and assemble into microparticles that are physically trapped within and toughen hydrogel networks.

Understanding pharmacokinetics using realistic computational models of fluid dynamics: biosimulation of drug distribution within the CSF space for intrathecal drugs.

We introduce how biophysical modeling in pharmaceutical research and development, combining physiological observations at the tissue, organ and system level with selected drug physiochemical properties, may contribute to a greater and non-intuitive understanding of drug pharmacokinetics and therapeutic design. Based on rich first-principle knowledge combined with experimental data at both conception and calibration stages, and leveraging our insights on disease processes and drug pharmacology, biophysical modeling may provide a novel and unique opportunity to interactively characterize detailed drug transport, distribution, and subsequent therapeutic effects. This innovative approach is exemplified through a three-dimensional (3D) computational fluid dynamics model of the spinal canal motivated by questions arising during pharmaceutical development of one molecular therapy for spinal cord injury.