Mathematical modelling of the evolution of protein distribution within single PLGA microspheres: prediction of local concentration profiles and release kinetics

Abstract

Protein release from poly(D,L-lactide-co-glycolide) (PLGA) microspheres in an aqueous environment is governed by the diffusion of the protein through an autocatalytically degrading polymeric matrix. Many attempts have been made to model the release rate of proteins from biodegrading matrices, but the transport parameters involved in the process are not fully established at the microscale level. The aim of this work was to develop a new mathematical model taking into account the temporal evolution of the radial protein distribution during release, and to provide physical insight into the relation between local transport features and microsphere degradation. The model was validated by comparing its predictions with the experimentally determined protein concentration profiles in PLGA microspheres loaded with tetramethylrhodamine-labelled bovine serum albumin (BSA-Rhod) as a model protein. Morphological studies were carried out by scanning electron microscopy (SEM), while release kinetics and time-dependent BSA-Rhod concentration profiles within the microspheres were studied by a confocal laser scanning microscopy (CLSM)-assisted technique. The model, based on a modification of Fick's second law of diffusion, could closely fit the experimental protein radial distribution profiles in the microspheres as a function of time. It is also a useful tool to ab initio design protein release devices using degrading matrices.

Encapsulation-free controlled release: Electrostatic adsorption eliminates the need for protein encapsulation in PLGA nanoparticles

“…Models of drug release from PLGA np usually consider polymer degradation, erosion, and diffusion of the drugs through the resulting water-filled pores as rate-determining ( 1 , 23 ). However, our results show very similar release profiles for three different proteins whether they are encapsulated in PLGA np or simply mixed with them, indicating that another mechanism must be involved.…”

Experimental Studies and Modeling of the Degradation Process of Poly(Lactic-co-Glycolic Acid) Microspheres for Sustained Protein Release

“…Figure 3 shows the CLSM images displaying the virtual sections of MS during degradation in the absence of the mechanical stress related to the blade during sectioning. The visual comparison with Figure 2 shows how, during their degradation, MS progressively lose fluorescence due to the release of BSA-Rhod [23,32,40]; at the same time, PLGA matrix progressively vanishes, still keeping the degrading MS an overall spherical geometry. Figure 3 shows the CLSM images displaying the virtual sections of MS during degradation in the absence of the mechanical stress related to the blade during sectioning.…”

“…The soluble oligomers diffuse outwards according to a process controlled by degradation and solubility [28], causing mass erosion of the MS matrix [30], as well as the progressive increase of the void volume inside MS [30,31]. This complex balance results into the erosion of PLGA MS, which is favored in the internal sections of the devices, while occurring at a lower extent at the border of microspheres [32].…”

Mathematical modeling of drug delivery from autocatalytically degradable PLGA microspheres — A review

“…Mollica et al [67] presented a model that described the time-dependent radial concentration profiles for two populations of a protein dispersed in a PLGA microsphere. The immobile fraction of protein was stationary in unopened pores not connected to the microsphere surface through hydrated pores.…”