A potential approach for decreasing the burst effect of protein from PLGA microspheres.

A central issue in controlled delivery of therapeutics from biodegradable microspheres is the immediate burst of drug release upon injection. This burst is often observed with microsphere systems made by the double emulsion (w/o/w) technique, and may be prevented by improving the drug distribution throughout the polymer matrix. To this end, protein and polymer (poly-lactide-co-glycolide or PLGA) were dissolved within the same solvent system, and micron-sized microspheres were created from this solution by spontaneous emulsification. Improved protein loading was achieved by ion-pairing the protein with charged surfactants to increase solubility in the single-phase solvent system. Both in vitro and in vivo results showed a much diminished burst: compared to microspheres made by double emulsion, it was reduced over 10-fold.

[1]  J. Rigelsford.  Handbook of Pharmaceutical Controlled release Technology , 2002 .

[2]  R. Zinkernagel,et al.  CD4+ T-cell–epitope escape mutant virus selected in vivo , 2001, Nature Medicine.

[3]  H. Takeuchi,et al.  Pulmonary delivery of insulin with nebulized DL-lactide/glycolide copolymer (PLGA) nanospheres to prolong hypoglycemic effect. , 1999, Journal of controlled release : official journal of the Controlled Release Society.

[4]  Yoshiaki,et al.  Preparation of poly(DL-lactide-co-glycolide) nanoparticles by modified spontaneous emulsification solvent diffusion method. , 1999, International journal of pharmaceutics.

[5]  R. Langer,et al.  Drug delivery and targeting. , 1998, Nature.

[6]  M. Manning,et al.  Hydrophobic Ion Pairing: Altering the Solubility Properties of Biomolecules , 1998, Pharmaceutical Research.

[7]  O'donnell,et al.  Preparation of microspheres by the solvent evaporation technique. , 1997, Advanced drug delivery reviews.

[8]  Yoshiaki,et al.  Influence of the Degrees of Hydrolyzation and Polymerization of Poly(vinylalchol)on the Preparation and Properties of Poly(DL-lactide-co-glycolide)nanoparticle. , 1997 .

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

[10]  A. Shahzamani,et al.  A month–long effect from a single injection of microencapsulated human growth hormone , 1996, Nature Medicine.

[11]  Simon Benita,et al.  The influence of process parameters on the PLA nanoparticle size distribution, evaluated by means of factorial design , 1995 .

[12]  Y. Kawashima,et al.  In vitro drug release behavior of D,L-lactide/glycolide copolymer (PLGA) nanospheres with nafarelin acetate prepared by a novel spontaneous emulsification solvent diffusion method. , 1994, Journal of pharmaceutical sciences.

[13]  A. Klibanov,et al.  Detergent-enabled transport of proteins and nucleic acids through hydrophobic solvents. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[14]  Yoshiaki,et al.  Preparations of biodegradable nanospheres of water-soluble and insoluble drugs with D, L-lactide/glycolide copolymer by a novel spontaneous emulsification solvent diffusion method, and the drug release behavior. , 1993 .

[15]  Robert Langer,et al.  Controlled Delivery Systems for Proteins Using Polyanhydride Microspheres , 1993, Pharmaceutical Research.

[16]  Robert Langer,et al.  Controlled Delivery Systems for Proteins Based on Poly(Lactic/Glycolic Acid) Microspheres , 1991, Pharmaceutical Research.

[17]  R. K. Rana,et al.  Release of Human Serum Albumin from Poly(lactide-co-glycolide) Microspheres , 1990, Pharmaceutical Research.

[18]  C. G. Pitt,et al.  The controlled parenteral delivery of polypeptides and proteins , 1990 .

[19]  D. Quintanar-Guerrero,et al.  Preparation techniques and mechanisms of formation of biodegradable nanoparticles from preformed polymers. , 1998, Drug development and industrial pharmacy.

[20]  A. Klibanov,et al.  Stability of Proteins and Their Delivery from Biodegradable Polymer Microspheres , 1996 .

[21]  J. Nutting,et al.  Interfacial Phenomena , 1959, Nature.