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.

Transport of phospholipid in silicone hydrogel contact lenses.

Characterization of the transport and release of phospholipids from a silicone hydrogel contact lens is required to assess the possible use of these lenses for phospholipid delivery to increase patient comfort. Contact lenses of silicone hydrogel composition were loaded with varying amounts of radiolabeled 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) from a solution of n-propanol. These lenses were eluted at 35°C into artificial tear fluid (ATF) or ATF containing varying amounts of DMPC. The amount of DMPC loaded into a lens is a linear function of the time of exposure to the DMPC/propanol solution. The initial rate of elution into ATF appears to be diffusion controlled for at least 10 h and is proportional to the amount of DMPC loaded. The elution rate decreases as the DMPC concentration in the ATF increases. The ease of loading and the controllable release of DMPC from silicone hydrogels presents the possibility of using such lenses to counter eye discomfort caused by inherently low levels of phospholipid in tears.

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 µg 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 µg of DMPC was loaded into the lenses. An average of nearly 1 µg 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.

Treatment of biofilm infections on implants with low-frequency ultrasound and antibiotics.

Medical implants are sometimes colonized by biofilm-forming bacteria, which are very difficult to treat effectively. The combination of gentamicin and ultrasonic exposure for 24 hours was previously shown to reduce the viability of Escherichia coli biofilms in vivo. This article shows that such treatment for 48 hours reduced viable E coli bacteria to nearly undetectable levels. However, when Pseudomonas aeruginosa biofilms were implanted and treated for 24 and 48 hours, no significant ultrasonic-enhanced reduction of viable bacteria was observed. The difference in response of these 2 organisms is attributed to greater impermeability and stability of the outer membrane of P aeruginosa.

Ultrasonic-enhanced gentamicin transport through colony biofilms of Pseudomonas aeruginosa and Escherichia coli.

The hypothesis that ultrasound increases antibiotic transport through biofilms of Escherichia coli and Pseudomonas aeruginosa was investigated using colony biofilms. Biofilms grown on membrane filters were transferred to nutrient agar containing 50 microg/ml gentamicin. A smaller filter was placed on top of the biofilm and a blank concentration disk was situated atop the filter. Diffusion of antibiotic through the biofilms was allowed for 15, 30, or 45 min at 37 degrees C. Some of these biofilms were exposed to 70-kHz ultrasound and others were not. Each concentration disk was then placed on a nutrient agar plate spread with a lawn of E. coli. The resulting zone of inhibition was used to calculate the amount of gentamicin that was transported through the biofilm into the disk. The E. coli and P. aeruginosa biofilms grown for 13 and 24 h were exposed to two different ultrasonic power densities. Ultrasonication significantly increased the transport of gentamicin through the biofilm. Insonation of biofilms of E. coli for 45 min more than doubled the amount of gentamicin compared to their noninsonated counterparts. For P. aeruginosa biofilms, no detectable gentamicin penetrated the biofilm within 45 min without ultrasound; however, when insonated (1.5 W/cm2) for 45 min, the disks collected more than 0.45 microg antibiotic. Ultrasonication significantly increased transport of gentamicin across biofilms that normally blocked or slowed gentamicin transport when not exposed to ultrasound. This enhanced transport may be partially responsible for the increased killing of biofilm bacteria exposed to combinations of antibiotic and ultrasound.

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.

Ultrasonically activated chemotherapeutic drug delivery in a rat model.

Systemic delivery of anticancer agents is accompanied by many unwanted side effects that can be mitigated by encapsulation of antineoplastic agents. However, encapsulation necessitates a technique for controlled delivery to the cancerous tissue. We have developed a novel drug delivery system that releases drug from stabilized micelles upon application of low-frequency ultrasound and that demonstrates efficacy using doxorubicin (Dox) to treat tumors in vivo. Forty-two BDIX rats were inoculated in each hind leg with a DHD/K12/TRb tumor cell line. Dox was encapsulated within stabilized Pluronic micelles and administered weekly i.v. to the rats starting 6 weeks after the tumor inoculations. One of the two tumors was exposed to low-frequency ultrasound for 1 h. Dox concentrations of 1.33, 2.67, and 8 mg/kg and ultrasound frequencies of 20 and 70 kHz were used for treatment. Tumor volume was measured with calipers and observed over the treatment time. Administration of encapsulated Dox at concentrations of 1.33 and 2.67 mg/kg was not lethal to the rats. Application of low-frequency ultrasound (both 20 and 70 kHz) significantly reduced the tumor size when compared with noninsonated controls (P = 0.0062) in the other leg for rats receiving encapsulated Dox. Significant tumor reduction was also noted for those rats receiving ultrasound and encapsulated Dox at 2.67 mg/kg (P = 0.017) and rats receiving Dox and ultrasound at 70 kHz (P = 0.029). We postulate that ultrasound releases the Dox from the micelles as they enter the insonated volume, and ultrasound could also assist the drug and/or carriers to extravasate and enter the tumor cells. Encapsulation of Dox using stabilized Pluronic micelles and localized release using low-frequency ultrasound show promise in offering controlled drug delivery in the treatment of tumors in a rat model.