Continuous Generation of Ethyl Cellulose Drug Delivery Nanocarriers from Microbubbles

Abstract

Purpose

To investigate a new microfluidic method for the continuous preparation of hollow-shell nanoparticles of a hydrophobic polymer and the simultaneous encapsulation within these of a hydrophilic active pharmaceutical ingredient.

Method

A specially designed and constructed microfluidic device which facilitates at a junction the impingement of two liquids flowing in capillaries kept 60° apart, one containing the polymer ethyl cellulose (EC) and the other active pharmaceutical ingredient amoxicillin, and a gas flowing in a capillary bisecting the two liquid flows, was used to continuously generate EC coated microbubbles at an outlet directly below the gas flow. The bubbles produce EC nanoparticles whilst encapsulating amoxicillin, and these were characterised by microscopy, zeta potential measurements, FTIR and UV spectroscopy and in vitro drug release and kinetic studies.

Results

The device produced ~5 × 106 microbubbles per minute from the surface of which EC nanocarriers were released spontaneously according to an evaporation-controlled mechanism. The gas pressure was very effective in controlling the size and size distribution of the nanocarriers.

Conclusions

Nanocarriers with diameter between 10 and 800 nm were continuously produced by controlling the gas pressure between 110 and 510 kPa. Depending on their size, particles were capable of encapsulating 65–88% of amoxicillin which was released over ~12 h.

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Acknowledgments and Disclosures

The authors wish to thank the Islamic Development Bank for supporting the doctoral research programme of Oguzhan Gunduz. They would also like to thank Kevin Reeves for the help with the scanning electron microscopes in the Archaeology Department at UCL and Dr Suguo Huo of the London Centre for Nanotechnology for the use of FIB.

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Correspondence to Mohan Edirisinghe.

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Video: Supplementary video showing the device and process.

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Gunduz, O., Ahmad, Z., Stride, E. et al. Continuous Generation of Ethyl Cellulose Drug Delivery Nanocarriers from Microbubbles. Pharm Res 30, 225–237 (2013). https://doi.org/10.1007/s11095-012-0865-7

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KEY WORDS

  • bubbles
  • drug delivery
  • microfluidic
  • nanocarriers