Modeling of the effect of cerebrospinal fluid flow modulation on locally delivered drugs in the brain.

Cerebrospinal fluid (CSF) plays a vital role in maintaining brain homeostasis and recent research has focused on elucidating the role that convective flow of CSF plays in brain health. This paper describes a computational compartmental model of how CSF dynamics affect drug pharmacokinetics in the rat brain. Our model implements a local, sustained release approach for drug delivery to the brain.

Erratum: Characterization of Mechanically Matched Hydrogel Coatings to Improve the Biocompatibility of Neural Implants.

A correction to this article has been published and is linked from the HTML version of this paper. The error has not been fixed in the paper.

Characterization of Mechanically Matched Hydrogel Coatings to Improve the Biocompatibility of Neural Implants.

Glial scar is a significant barrier to neural implant function. Micromotion between the implant and tissue is suspected to be a key driver of glial scar formation around neural implants. This study explores the ability of soft hydrogel coatings to modulate glial scar formation by reducing local strain.

A three dimensional in vitro glial scar model to investigate the local strain effects from micromotion around neural implants.

Glial scar formation remains a significant barrier to the long term success of neural probes. Micromotion coupled with mechanical mismatch between the probe and tissue is believed to be a key driver of the inflammatory response. In vitro glial scar models present an intermediate step prior to conventional in vivo histology experiments as they enable cell-device interactions to be tested on a shorter timescale, with the ability to conduct broader biochemical assays.

Single compartment drug delivery.

Drug design is built on the concept that key molecular targets of disease are isolated in the diseased tissue. Systemic drug administration would be sufficient for targeting in such a case. It is, however, common for enzymes or receptors that are integral to disease to be structurally similar or identical to those that play important biological roles in normal tissues of the body.

Targeting extracellular DNA to deliver IGF-1 to the injured heart.

There is a great need for the development of therapeutic strategies that can target biomolecules to damaged myocardium. Necrosis of myocardium during a myocardial infarction (MI) is characterized by extracellular release of DNA, which can serve as a potential target for ischemic tissue. Hoechst, a histological stain that binds to double-stranded DNA can be conjugated to a variety of molecules.

Maleimide cross-linked bioactive PEG hydrogel exhibits improved reaction kinetics and cross-linking for cell encapsulation and in situ delivery.

Engineered polyethylene glycol-maleimide matrices for regenerative medicine exhibit improved reaction efficiency and wider range of Young’s moduli by utilizing maleimide cross-linking chemistry. This hydrogel chemistry is advantageous for cell delivery due to the mild reaction that occurs rapidly enough for in situ delivery, while easily lending itself to “plug-and-play” design variations such as incorporation of enzyme-cleavable cross-links and cell-adhesion peptides.

Delivering regenerative cues to the heart: cardiac drug delivery by microspheres and peptide nanofibers.

Our understanding of signaling pathways and cues vital for cardiac regeneration is being refined by laboratories worldwide. As various mechanisms enabling cardiac regeneration are becoming elucidated, delivery vehicles suited for these potential therapeutics must also be developed. This review focuses on advances in two technologies, novel degradable microspheres for controlled release systems and self-assembling peptide nanofibers for cell and factor delivery.

Surface functionalization of polyketal microparticles with nitrilotriacetic acid-nickel complexes for efficient protein capture and delivery.

Microparticle drug delivery systems have been used for over 20 years to deliver a variety of drugs and therapeutics. However, effective microencapsulation of proteins has been limited by low encapsulation efficiencies, large required amounts of protein, and risk of protein denaturation. In this work, we have adapted a widely used immobilized metal affinity protein purification strategy to non-covalently attach proteins to the surface of microparticles.

The delivery of superoxide dismutase encapsulated in polyketal microparticles to rat myocardium and protection from myocardial ischemia-reperfusion injury.

Oxidative stress is increased in the myocardium following infarction and plays a significant role in death of cardiac myocytes, leading to cardiac dysfunction. Levels of the endogenous antioxidant Cu/Zn-superoxide dismutase (SOD1) decrease following myocardial infarction. While SOD1 gene therapy studies show promise, trials with SOD1 protein have had little success due to poor pharmacokinetics and thus new delivery vehicles are needed.

Sustained release of a p38 inhibitor from non-inflammatory microspheres inhibits cardiac dysfunction.

Cardiac dysfunction following acute myocardial infarction is a major cause of death in the world and there is a compelling need for new therapeutic strategies. In this report we demonstrate that a direct cardiac injection of drug-loaded microparticles, formulated from the polymer poly(cyclohexane-1,4-diylacetone dimethylene ketal) (PCADK), improves cardiac function following myocardial infarction. Drug-delivery vehicles have great potential to improve the treatment of cardiac dysfunction by sustaining high concentrations of therapeutics within the damaged myocardium.

Microfluidic-based cell sorting of Francisella tularensis infected macrophages using optical forces.

We have extended the principle of optical tweezers as a noninvasive technique to actively sort hydrodynamically focused cells based on their fluorescence signal in a microfluidic device. This micro fluorescence-activated cell sorter (microFACS) uses an infrared laser to laterally deflect cells into a collection channel. Green-labeled macrophages were sorted from a 40/60 ratio mixture at a throughput of 22 cells/s over 30 min achieving a 93% sorting purity and a 60% recovery yield.

Towards developing surface eroding poly(alpha-hydroxy acids).

We have prepared a library of biodegradable polyesters derived from poly(alpha-hydroxy acids) (PHAs) that appear to primarily exhibit surface erosion behavior. This was achieved by increasing the hydrophobicity of the polymers in two distinct steps, namely: macromer formation and a coupling step. In the first step, macromerdiols (MDs) with varying lipophilicities were prepared by polymerization of L-lactide or mixture of L-lactide and glycolide (3/1 by mole) to various lengths (n = 10, 20, 30, and 40) using alkanediols of increasing C-chain length (C6, C8, and C12) as initiators in the presence of Tin(II) catalyst.