title: 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.
authors.affiliation: Department of Engineering, University of Ferrara, via Saragat 1, 44100 Ferrara, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Mollica
authors.forename: Marco
authors.initials: M
authors.lastname: Biondi
authors.forename: Sara
authors.initials: S
authors.lastname: Muzzi
authors.forename: Francesca
authors.initials: F
authors.lastname: Ungaro
authors.forename: Fabiana
authors.initials: F
authors.lastname: Quaglia
authors.forename: Maria Immacolata
authors.initials: MI
authors.lastname: La Rotonda
authors.forename: Paolo Antonio
authors.initials: PA
authors.lastname: Netti
mesh_terms: D000465:Algorithms; D000818:Animals; D002417:Cattle; D003198:Computer Simulation; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry*; D008422:Materials Testing; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D008962:Models, Theoretical; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry*; D012235:Rhodamines / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000737:chemistry
chemical_list: D011108:Polymers; D011506:Proteins; D012235:Rhodamines; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D012710:Serum Albumin, Bovine; D019344:Lactic Acid; C005358:tetramethylrhodamine