Defining drug and target protein distributions after stent-based drug release: Durable versus deployable coatings.

Background: Innovations in drug eluting stent designs make it increasingly important to develop models for differentiating performance through spatial definition of drug, receptor binding and cell state.

Methods: Two designs of sirolimus analog eluting stents were implanted into porcine coronary arteries for 28, 60 or 90 days (n = 9/time point), durable coating (Xience) and deployable absorbable coating (MiStent). Explanted arteries were evaluated for drug content (n = 3/time point) by LC-MS/MS and for drug and target protein (mTOR) distributions by immunofluorescence (IF, n = 6/time point).

Reduction of adhesion formation by postoperative administration of ionically cross-linked hyaluronic acid.

Objective: To examine the efficacy of various formulations of hyaluronic acid (HA), including HA ionically cross-linked with trivalent iron, in animal models of adhesion formation.

Design: Hyaluronic acid formulation of varying concentrations and cross-linked densities were prepared and evaluated in a rabbit uterine horn model and a rabbit sidewall model.

Setting: ETHICON, Inc.

Assessment of full-thickness wounds in the genetically diabetic mouse for suitability as a wound healing model.

While using the diabetic C57BL/KsJ db/db mouse as a wound healing model, we encountered several repair patterns which affect its suitability as a predictive screening model for certain indications. For example, wound contraction, albeit impaired, was found to be particularly dependent on bandaging technique and vehicle type. Wounds which had been continuously occluded with Opsite dressings had a high relative variability in contraction, and there was a tendency toward reduced contraction, suggesting that the dressings were acting as a splint.

Efficacy of tolmetin sodium for adhesion prevention in rabbit and rat models.

Tolmetin sodium's efficacy in preventing primary adhesions was evaluated in two adhesion models each in two species: (1) rabbit uterine horn, (2) rat uterine horn, (3) rabbit peritoneal side wall, and (4) rat peritoneal side wall. In each model a single instillation of tolmetin sodium solution into the peritoneal cavity at the time of surgery effectively reduced adhesion formation. This efficacy extended over a wide range of concentrations, volumes, and total dosages, and was similar in rabbits and rats.

Evaluation of PDGF-BB, PDGF-AA, bFGF, IL-1, and EGF dose responses in polyvinyl alcohol sponge implants assessed by a rapid histologic method.

Polyvinyl alcohol sponge implants were used in rats, mice, and guinea pigs to determine dose responses of growth factors. Eight differently treated sponges per rat or guinea pig (4/mouse) were injected with test material on alternate days and evaluated at day 8. Much of the observed response occurred in and around the capsule and was manifest as densely cellular granulation tissue.