title: Polymer and microsphere blending to alter the release of a peptide from PLGA microspheres.
abstract: The objective of this study was to evaluate the effect of polymer and microsphere blending in achieving both a sufficient initial release and a desired continuous release of a peptide from poly(D, L-lactide-co-glycolide) microspheres. Leuprolide acetate loaded hydrophilic 50:50 PLGA microspheres were prepared by a solvent-extraction/evaporation process and were characterized for their drug load, bulk density, size distribution, surface area, surface morphology, in vitro drug release, and in vivo efficacy. Combining PLGA polymers that varied in their molecular weights in various ratios yielded microspheres with varied drug release profiles commensurate with the hydration tendencies of the polymers. Increasing the component of lower molecular weight 50:50 hydrophilic PLGA polymer, 8.6 kDa increased the initial drug release. A similar microsphere formulation prepared instead with blending microspheres from individual polymers showed a similar increase. In an animal model, microspheres obtained from polymer or microsphere blends attained a faster onset of testosterone suppression as compared to microspheres from higher molecular weight 50:50 hydrophilic PLGA polymer, 28.3 kDa, alone. These studies illustrated the feasibility of blending polymers or microspheres of varied characteristics in achieving modified drug release. In particular the increased initial release of the peptide could help avoid the therapeutic lag phase usually observed with microencapsulated macromolecules.
authors.affiliation: Dynavax Technologies Corporation, Berkley, CA, USA.
authors.forename: H B
authors.initials: HB
authors.lastname: Ravivarapu
authors.forename: K
authors.initials: K
authors.lastname: Burton
authors.forename: P P
authors.initials: PP
authors.lastname: DeLuca
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical; D019344:Lactic Acid / Q000008:administration & dosage*; D016729:Leuprolide / Q000008:administration & dosage*; D008297:Male; D008863:Microspheres; D008970:Molecular Weight; D011100:Polyglycolic Acid / Q000008:administration & dosage*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000097:blood; D014783:Viscosity
chemical_list: D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D013739:Testosterone; D016729:Leuprolide