Accelerating protein release from microparticles for regenerative medicine applications

Abstract

There is a need to control the spatio-temporal release kinetics of growth factors in order to mitigate current usage of high doses. A novel delivery system, capable of providing both structural support and controlled release kinetics, has been developed from PLGA microparticles. The inclusion of a hydrophilic PLGA-PEG-PLGA triblock copolymer altered release kinetics such that they were decoupled from polymer degradation. A quasi zero order release profile over four weeks was produced using 10% w/w PLGA-PEG-PLGA with 50:50 PLGA whereas complete and sustained release was achieved over ten days using 30% w/w PLGA-PEG-PLGA with 85:15 PLGA and over four days using 30% w/w PLGA-PEG-PLGA with 50:50 PLGA. These three formulations are promising candidates for delivery of growth factors such as BMP-2, PDGF and VEGF. Release profiles were also modified by mixing microparticles of two different formulations providing another route, not previously reported, for controlling release kinetics. This system provides customisable, localised and controlled delivery with adjustable release profiles, which will improve the efficacy and safety of recombinant growth factor delivery.

Graphical abstract

Supplementary Fig. 1

Size distributions (left) and SEM images (right) of protein loaded (1% w/w) microparticles formulated from 50:50 PLGA and a PLGA–PEG–PLGA copolymer. Concentrations of the PLGA–PEG–PLGA component were varied: 0% (A and B), 10% (C and D), 20% (E and F) and 30% (G and H).

Fig. 1

Morphology of microparticles formulated from 85:15 PLGA with 10% w/w PLGA–PEG–PLGA, with size distributions and SEM images of the blank (no protein) microparticles (A and B) and protein loaded (1% w/w) microparticles (C and D).

Fig. 2

Cumulative release of HSA/lysozyme (1% w/w) from microparticles formulated from (A) 50:50 PLGA with 30% (■), 10% (▼) and 0% (●) of a PLGA–PEG–PLGA copolymer and (B) 85:15 PLGA with 30% (□), 10% (▽) and 0% (○) of a PLGA–PEG–PLGA copolymer. Release profiles of 50:50 PLGA with 30% (■), 85:15 PLGA with 30% (□) and 50:50 PLGA with 10% (▼) over 14 days are shown in (C). Data represent mean ± SD for n = 3.

Fig. 3

Cumulative release of HSA/lysozyme (1% w/w) from microparticles formulated from 50:50 PLGA with 30% (■) and 10% (▼) of a PLGA–PEG–PLGA copolymer and a mixture of these two formulations (1:1 ratio) (○). Data represent mean ± SD for n = 9.

Fig. 4

Cumulative release of HSA/lysozyme (1% w/w) (▼) and HSA/BMP-2 (1% w/w) (▽) from microparticles formulated from 50:50 PLGA with 10% w/w PLGA–PEG–PLGA copolymer. Data represent mean ± SD for n = 3.