Jared L. Nelson

Drug delivery in polymeric micelles: from in vitro to in vivo.

A new drug delivery modality was developed based on drug encapsulation in polymeric micelles followed by a controlled release at the tumor site triggered by ultrasound focused on the tumor. Ultrasound not only released drug from micelles but also enhanced the local uptake of both free and encapsulated drug by tumor cells, thus providing effective drug targeting. The significant success of in vitro studies of this new drug delivery technique warranted extending studies to animal experiments. Here the results of the in vitro studies of the above technique are summarized and the first in vivo experiments using colon cancer model in rats are reported. The in vivo results showed that application of low-frequency ultrasound (20 and 70 kHz) significantly reduced the tumor size when compared with non-insonated controls; this result indicated in vivo drug targeting to tumors by ultrasound.

Pulsed Ultrasound Enhances the Killing of Escherichia coli Biofilms by Aminoglycoside Antibiotics In Vivo

ABSTRACT Escherichia coli biofilms on two polyethylene disks were implanted subcutaneously into rabbits receiving systemic gentamicin. Ultrasound was applied for 24 h to one disk. Both disks were removed, and viable bacteria were counted. Pulsed ultrasound significantly reduced bacterial viability below that of nontreated biofilms without damage to the skin.

Ultrasonically enhanced vancomycin activity against Staphylococcus epidermidis biofilms in vivo

Infection of implanted medical devices by Gram-positive organisms such as Staphylococcus ssp. is a serious concern in the biomaterial community. In this research the application of low frequency ultrasound to enhance the activity of vancomycin against implanted Staphylococcus epidermidis biofilms was examined. Polyethylene disks covered with a biofilm of S. epidermidis were implanted subcutaneously in rabbits on both sides of their spine. The rabbits received systemic vancomycin for the duration of the experiment. Following 24 h of recovery, one disk was insonated for 24 or 48 h while the other was a control. Disks were removed and viable bacteria counted. At 24 h of insonation, there was no difference in viable counts between control and insonated biofilms, while at 48 h of insonation there were statistically fewer viable bacteria in the insonated biofilm. The S. epidermidis biofilms responded favorably to combinations of ultrasound and vancomycin, but longer treatment times are required for this Gram-positive organism than was observed previously for a Gram-negative species.

Loading and release of a phospholipid from contact lenses.

Purpose. Dry eye syndrome has been associated with the lack of phospholipids in the tear film, leading to disruption of the tear film and subsequent irritation. This study explores the feasibility of loading a phospholipid into contact lenses for controlled release to the eye. Methods. Silicone hydrogel contact lenses were loaded with 33 &mgr;g of radio-labeled 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) from a solution of n-propanol. The loaded lenses were soaked at 35°C in either water or artificial tear solution (ATF), and the elution of DMPC was quantified by scintillation counting. Results. About 33 &mgr;g of DMPC was loaded into the lenses. An average of nearly 1 &mgr;g of DMPC was eluted into ATF within the first 10 h. Elution was about five times faster in ATF than in water. The elution appears to be controlled by the diffusivity of DMPC in the contact lens and the properties of the elution solution. Conclusions. This type of lens technology may have the potential to deliver phospholipids to help address contact lens-related dryness through lipid layer stabilization.

Extended elution of phospholipid from silicone hydrogel contact lenses

Characterization of phospholipid release from an experimental reusable wear silicone hydrogel contact lens was performed to assess the possible use of these lenses for phospholipid delivery to increase eye comfort to patients who prefer reusable wear lenses. Contact lenses were loaded with 200 μg of radio-labeled 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) from a solution of n-propanol. To simulate 30 days of diurnal use with overnight cleaning, these lenses were eluted for 16 h at 35 °C into artificial tear fluid (ATF), and then eluted at room temperature (~22 °C) for 8 h in one of three commercial contact lens cleaning systems. This was repeated for 30 days. The elution of DMPC into ATF was greater on the first day, followed by a fairly constant amount of elution each day thereafter. The type of cleaning system had a statistically significant effect on the elution rate during daily exposure to ATF. The rate of elution into cleaning solutions did not show any enhanced elution on the first day; there was a fairly constant elution rate. Again, the type of cleaning system significantly influenced the elution rate into the nightly cleaner.