In vitro performance of dye-loaded microsphere-based controlled release technologies synthesized via electrospray atomization

Malik, S.; Ng, W.; Bowen, J.; Tang, J.; Gomez, A.; Kenyon, A. J. and Day, R. M. (2015). In vitro performance of dye-loaded microsphere-based controlled release technologies synthesized via electrospray atomization. In: 3rd International Conference on Nanotechnology in Medicine, 23-25 Nov 2015, Manchester, UK.

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Abstract

Electrospray (ES) atomization has proven to be a versatile method to manufacture particles, giving tight control over size with quasi-monodisperse size distributions. It is a liquid atomisation technique that generates a monodisperse population of highly charged liquid droplets over a broad size range. Here, we successfully demonstrate a well-controlled single-step synthesis of biodegradable, mesoporous polymeric microspheres using ES technology, and validate their potential as controlled release vehicles. Poly(lactic-co-glycolic acid) (PLGA) was chosen as the model carrier of the encapsulated dye agent due to its attractive properties: (a) mechanical stability, (b) biocompatibility, (c) it’s recognition as an FDA-approved delivery system for parenteral administration [1].

We show how morphology, structure and porosity of resulting microspheres can be controlled by varying the flow rate (Q) and, consequently, the size of the polymeric carriers. We demonstrate examples in which the particle size and porosity affect release kinetics and the SEM images reveal how PLGA degradation is hydrolytically influenced over seven days. The microspheres manufactured here have successfully demonstrated long-term delivery (i.e. 1 week) of an active agent enabling sustained release of the dye without excessive physical degradation. Thermogravimetry (TG) verified this with zero mass loss up to 37°C (and above). Dissolution studies reveal diffusion of the encapsulated agent in two distinct phases in the cumulative release profile: a first phase in which the release is dominated by diffusion and a second phase with a slower release related to the erosion of the polymer matrix. The study reveals a clear dependence of microsphere size (and therefore porosity) on the residual release of the encapsulated dye.

[1] S. Mitragotri, P.A. Burke and R. Langer, Nat. Rev. Drug Discov., 13, 655 (2014).

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