Near-infrared-actuated devices for remotely controlled drug delivery

A reservoir that could be remotely triggered to release a drug would enable the patient or physician to achieve on-demand, reproducible, repeated, and tunable dosing. Such a device would allow precise adjustment of dosage to desired effect, with a consequent minimization of toxicity, and could obviate repeated drug administrations or device implantations, enhancing patient compliance. It should exhibit low off-state leakage to minimize basal effects, and tunable on-state release profiles that could be adjusted from pulsatile to sustained in real time. Despite the clear clinical need for a device that meets these criteria, none has been reported to date to our knowledge. To address this deficiency, we developed an implantable reservoir capped by a nanocomposite membrane whose permeability was modulated by irradiation with a near-infrared laser. Irradiated devices could exhibit sustained on-state drug release for at least 3 h, and could reproducibly deliver short pulses over at least 10 cycles, with an on/off ratio of 30. Devices containing aspart, a fast-acting insulin analog, could achieve glycemic control after s.c. implantation in diabetic rats, with reproducible dosing controlled by the intensity and timing of irradiation over a 2-wk period. These devices can be loaded with a wide range of drug types, and therefore represent a platform technology that might be used to address a wide variety of clinical indications

A two-component pre-seeded dermal-epidermal scaffold

We have developed a bilayered dermal-epidermal scaffold for application in the treatment of full-thickness skin defects. The dermal component gels in situ and adapts to the lesion shape, delivering human dermal fibroblasts in a matrix of fibrin and cross-linked hyaluronic acid modified with a cell adhesion-promoting peptide. Fibroblasts were able to form a tridimensional matrix due to material features such as tailored mechanical properties, presence of protease-degradable elements and cell-binding ligands. The epidermal component is a robust membrane containing cross-linked hyaluronic acid and poly-l-lysine, on which keratinocytes were able to attach and to form a monolayer. Amine-aldehyde bonding at the interface between the two components allows the formation of a tightly bound composite scaffold. Both parts of the scaffold were designed to provide cell-type-specific cues to allow for cell proliferation and form a construct that mimics the skin environment.D.S.K. acknowledges funding from the Biotechnology Research Endowment from the Department of Anesthesiology at Boston Children's Hospital. I.P.M. acknowledges the Portuguese Foundation for Science and Technology for the grant BD/39396/2007 and the MIT-Portugal Program. D.G. acknowledges the Swiss National Science Foundation for a post-doctoral fellowship (PBGEP3-129111). B.P.T. acknowledges an NIR Ruth L. Kirschstein National Research Service Award (F32GM096546)

Depth-dependent photodegradation of marine dissolved organic matter.

Marine dissolved organic matter (DOM) in surface and deep waters of the eastern Atlantic Ocean and Sargasso Sea was analyzed by excitation emission matrix (EEM) fluorescence spectroscopy and parallel factor analysis (PARAFAC). Photo-degradation with semi-continuous monitoring of EEMs and absorbance spectra was used to measure the photo-degradation kinetics and changes of the PARAFAC components in a depth profile of DOM at the Bermuda Atlantic Time Series (BATS) station in the Sargasso Sea. A five component model was fit to the EEMs, which included traditional terrestrial-like, marine-like, and protein-like components. Terrestrial-like components showed the expected high photo-reactivity, but surprisingly, the traditional marine-like peak showed slight photo-production in surface waters, which may account for its prevalence in marine systems. Surface waters were depleted in photo-labile components while protein-like fluorescent components were enriched, consistent with previous studies. Ultra-high resolution mass spectrometry detected unique aliphatic compounds in the surface waters at the BATS site, which may be photo-produced or photo-stable. Principle component and canonical analysis showed strong correlations between relative contributions of unsaturated/aromatic molecular formulas and depth, with aliphatic compounds more prevalent in surface waters and aromatic compounds in deep waters. Strong correlations were seen between these aromatic compounds and humic-like fluorescent components. The rapid photo-degradation of the deep-sea fluorescent DOM in addition to the surface water relative depletion of aromatic compounds suggests that deep-sea fluorescent DOM may be too photochemically labile to survive during overturning circulation