Effect of protein molecular weight on release from micron-sized PLGA microspheres

Quantitative multi-agent models for simulating protein release from PLGA bioerodible nano- and microspheres

“…A comparatively simple protein example like the lysozyme (13.4 kDa), has a diameter of 3.2 nm [20]. Diffusion measurements in PLGA micro-and nanospheres encapsulating lysozymes involve pore sizes < 20 nm [9], so it was reasonable to describe diffusion in terms of individual random walks of molecules, rather than by transport of matter through surfaces. Experimental studies [9], have revealed that, in general, the initial pores have 5 -80 nm in diameter, (proportional to the size of the encapsulated proteins).…”

“…Diffusion measurements in PLGA micro-and nanospheres encapsulating lysozymes involve pore sizes < 20 nm [9], so it was reasonable to describe diffusion in terms of individual random walks of molecules, rather than by transport of matter through surfaces. Experimental studies [9], have revealed that, in general, the initial pores have 5 -80 nm in diameter, (proportional to the size of the encapsulated proteins). Equally, other experimental studies have reported cases of spheres with initial occlusions much larger than the Stokes-Einstein diameter of the microencapsulated molecule [3,13].…”

“…The assumptions which apply to all models developed here are based on available experimental data [9]. The polymeric particles, modelled in 3D space, are considered to be completely spherical.…”

“…Besides the fact that it is non-toxic (PLGA nanospheres can be 16 times more effective for cell viability than the free drug, [5]), this material has proved capable of easy encapsulation [5] and subsequent release of drug (especially of pharmaceutically active proteins), in a sustained manner. Experimental studies such as [5,9,10] demonstrate the potential for encapsulation and sustained release of a wide variety of proteins from PLGA spheres.…”

“…Almost all known modelling approaches available [11,12,14] consider homogeneous distributions of the pores and of proteins in the spheres, experiments have indicated that this may not realistically describe the majority of cases [9,19], with internal configuration of the spheres subject to heterogeneity. In further discussion of microspheres properties, [13] assumes that adsorption of macromolecules to the surface of the microsphere (or to the large occlusions inside the spheres), suggesting an uneven distribution of the macromolecule in the volume of the sphere.…”