Protein encapsulation and release from poly(lactide-co-glycolide) microspheres: effect of the protein and polymer properties and of the co-encapsulation of surfactants.

Despite the recognised role of the poly(lactide-co-glycolide) (PLGA) in the encapsulation and release of proteins from PLGA microspheres, the importance that the characteristics of the protein have in these processes has not yet been sufficiently investigated. The aim of this work was to study the simultaneous effect of the protein and PLGA properties and of the microencapsulation process on the physicochemical and in vitro release characteristics of protein-loaded PLGA microspheres. Two model proteins of different isoelectric points (pI), bovine serum albumin (BSA) (pI = 4.6) and lysozyme (LZM) (pI = 11.2), and two different molecular weights (Mw) of PLGA were selected. Microspheres were prepared using the water-in-oil-in-water (w/o/w) solvent extraction and the oil-in-oil (o/o) solvent evaporation techniques. Results showed that BSA was efficiently encapsulated independent of the PLGA Mw, whereas the encapsulation of LZM was favoured with the low Mw PLGA. The co-encapsulation of a surfactant (poloxamer 188 or 331) reduced the protein encapsulation efficiency, especially of BSA. These results suggested that the tensoactive properties of the protein and its affinity for the PLGA are major determinants of the protein encapsulation. Both proteins released faster from the microspheres prepared by the o/o solvent evaporation procedure, with respect to those prepared by the w/o/w solvent extraction technique. In addition, both polymer Mw and protein type had an effect on the protein release rate. The release rate of both proteins, in the absence of a surfactant, was faster from the low Mw PLGA microspheres. However, the release rate constant was higher for BSA than for LZM irrespective of the PLGA Mw. In addition, the co-encapsulation of a surfactant led, in most cases, to a faster release of the encapsulated protein. To conclude, these results suggest that protein release from PLGA microspheres is not only governed by the PLGA erosion rate and protein diffusion through the water-filled channels, but is highly affected by the protein properties and its possible interaction with PLGA and its degradation products.

[1]  María J. Alonso,et al.  Development and characterization of protein-loaded poly(lactide-co-glycolide) nanospheres , 1997 .

[2]  Gerhard Winter,et al.  Microencapsulation of rh-erythropoietin, using biodegradable poly(d,l-lactide-co-glycolide): protein stability and the effects of stabilizing excipients , 1997 .

[3]  R. Langer,et al.  An explanation for the controlled release of macromolecules from polymers , 1985 .

[4]  Jean-Pierre Benoit,et al.  Bovine serum albumin release from poly(α-hydroxy acid) microspheres: effects of polymer molecular weight and surface properties , 1997 .

[5]  R. Mehta,et al.  Adsorption of peptides to poly(D,L-lactide-co-glycolide): 1. Effect of physical factors on the adsorption , 1996 .

[6]  Robert J. Linhardt,et al.  Influence of formulation methods on the in vitro controlled release of protein from poly (ester) microspheres , 1991 .

[7]  S. Davis,et al.  The preparation and characterization ofpoly(lactide-co-glycolide) microparticles: III. Microparticle/polymer degradation rates and the in vitro release of a model protein , 1994 .

[8]  Joseph D. Andrade,et al.  Protein adsorption and materials biocompatibility: A tutorial review and suggested hypotheses , 1986 .

[9]  T. Park,et al.  Stability and release of bovine serum albumin encapsulated within poly(d,l-lactide-co-glycolide) microparticles , 1996 .

[10]  T. Kondo,et al.  Adsorption of bovine serum albumin on positively and negatively charged microcapsules , 1992 .

[11]  R. Jerome,et al.  Effect of the emulsion stability on the morphology and porosity of semicrystalline poly l-lactide microparticles prepared by w/o/w double emulsion-evaporation , 1994 .

[12]  T. Kissel,et al.  INJECTABLE BIODEGRADABLE MICROSPHERES FOR VACCINE DELIVERY , 1996 .

[13]  Smadar Cohen,et al.  Characterization of PLGA microspheres for the controlled delivery of IL-1α for tumor immunotherapy , 1997 .

[14]  Y. Ikada,et al.  Lactic acid oligomer microspheres containing hydrophilic drugs. , 1990, Journal of pharmaceutical sciences.

[15]  R. Mehta,et al.  Adsorption of peptides to poly(D,L-lactide-co-glycolide): 2. Effect of solution properties on the adsorption , 1996 .

[16]  R. Jerome,et al.  Polylactide Microparticles Prepared by Double Emulsion-Evaporation: II. Effect of the Poly(Lactide-co-Glycolide) Composition on the Stability of the Primary and Secondary Emulsions , 1995 .

[17]  J. Resau,et al.  Characterization and morphological analysis of protein-loaded poly(lactide-co-glycolide) microparticles prepared by water-in-oil-in-water emulsion technique , 1994 .

[18]  W. Norde,et al.  Adsorption of proteins from solution at the solid-liquid interface. , 1986, Advances in colloid and interface science.

[19]  Robert E. Johnson,et al.  Stability of atriopeptin III in poly(d,l-lactide-co-glycolide) microspheres , 1991 .