Abstract

BackgroundMicro bubbles were initially introduced as contrast agents for ultrasound examinations as they are able to modify the signal-to-noise ratio in imaging, thus improving the assessment of clinical information on human tissue. Recent developments have demonstrated the feasibility of using these bubbles as drug carriers in localized delivery. In micro fluidics devices for generation of micro bubbles, the bubbles are formed at interface of liquid gas through a strangulation process. A device that uses these features can produce micro bubbles with small size dispersion in a single step.MethodsA T-junction micro fluidic device constructed using 3D prototyping was made for the production of mono dispersed micro bubbles. These micro bubbles use sunflower oil as a lipid layer. Stability studies for micro bubbles with diameters different generated from a liquid phase of the same viscosity were conducted to evaluate whether micro bubbles can be used as drug carriers. The biocompatibility of coating layer, the ability to withstand environmental pressure variations combined with echogenicity, are key factors that they can safely play the role of drug transporters.ResultsThe normal distribution curve with small dispersion of the diameter of bubbles validates the process of generating micro bubbles with low value of variation coefficient, i.e., 0.381 at 1.90%. The results also showed the feasibility of using sunflower oil as the lipid matrix with stable population of bubbles over 217 minutes for micro bubbles with an average diameter of 313.04 μm and 121 minutes for micro bubbles with an average diameter of 73.74 μm, considering bubbles with air as gaseous phase.ConclusionThe results indicate that the micro fluidic device designed can be used for producing micro bubbles with low variation coefficient using sunflower oil as a coating of micro bubbles. These carriers were stable for periods of time that are long enough for clinical applications even when regular air is used as the gas phase. Improved stability can be achieved when biocompatible gas with lower permeability is used.

Highlights

  • Micro bubbles were initially introduced as contrast agents for ultrasound examinations as they are able to modify the signal-to-noise ratio in imaging, improving the assessment of clinical information on human tissue

  • Recent developments have demonstrated the feasibility of using these bubbles as drug carriers with an interesting feature which is appropriated for spatially limited treatment of diseases [1,2]

  • The statistical analysis of the process of formation of micro bubbles to the mentioned situation points to a variation coefficient of 1.90%, demonstrating the device’s ability to produce micro bubbles with a high degree of uniformity in relation to the diameter

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Summary

Introduction

Micro bubbles were initially introduced as contrast agents for ultrasound examinations as they are able to modify the signal-to-noise ratio in imaging, improving the assessment of clinical information on human tissue. Recent developments have demonstrated the feasibility of using these bubbles as drug carriers with an interesting feature which is appropriated for spatially limited treatment of diseases [1,2]. Well-known for its use in real-time imaging without dangerous irradiation of tissues, ultrasound can be used to control the drug delivery when the drug is carried by a micro bubble. This type of therapeutic application is a promising treatment modality, in the cases when high concentrations of drugs are commonly administered, causing undesirable systemic side effects. There are a few challenges ahead, and they are: (a) find compatible materials (drugs) that can be introduced into the bubbles (b) generation of bubbles with diameters smaller than 10 microns that could be introduced into the bloodstream without causing venous air embolism in the patient (c) generation of stable bubbles between the period of their generation, handling and use and (d) generation of monodispersed bubbles to increase the response to the ultrasonic field and a subsequent fragmentation

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