title: Conformational stability of a model protein (bovine serum albumin) during primary emulsification process of PLGA microspheres synthesis.
abstract: The goal of this study was to investigate the conformational stability of a model protein, bovine serum albumin (BSA), during the primary emulsification process of poly(D,L-lactide-co-glycolide) (PLGA) microspheres preparation. Differential scanning calorimeter (DSC) was utilized to assess the conformational structure of BSA during primary emulsification in the presence and absence of PLGA. Three excipients [i.e. mannitol, hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and sodium dodecyl sulfate (SDS)] were investigated for their stabilizing effect on BSA during emulsification process. The DSC profile of intact BSA was best fitted by a non-2-state model with two peaks, which have midpoint temperatures (T(m1), 60.9 +/- 0.4 degrees C and T(m2), 66.4 +/- 1.0 degrees C), respectively, and a total calorimetric enthalpy Delta H(tot) of 599 +/- 42 kJ/mol. After emulsifying BSA aqueous solution with methylene chloride, an additional apparent peak at a higher temperature was observed. The T(m) of this peak was 77.4 +/- 0.8 degrees C. HP-beta-CD was able to suppress the occurrence of an additional peak, whereas mannitol failed. SDS increased the thermal stability of BSA dramatically. Furthermore, HP-beta-CD increased BSA recovery from 72 +/- 8% to 89 +/- 7% after extraction from w/o in the presence of PLGA. These results provided evidence that HP-beta-CD could be a promising excipient for conformational stability of BSA during synthesis of PLGA microspheres.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo, ND 58105, USA.
authors.forename: Feirong
authors.initials: F
authors.lastname: Kang
authors.forename: Jagdish
authors.initials: J
authors.lastname: Singh
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D002152:Calorimetry, Differential Scanning; D003505:Cyclodextrins / Q000737:chemistry; D004655:Emulsions; D005079:Excipients / Q000737:chemistry; D019344:Lactic Acid / Q000737:chemistry*; D008353:Mannitol / Q000737:chemistry; D008863:Microspheres; D011092:Polyethylene Glycols; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D011487:Protein Conformation; D012710:Serum Albumin, Bovine / Q000737:chemistry*; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry; D047392:beta-Cyclodextrins
chemical_list: D003505:Cyclodextrins; D004655:Emulsions; D005079:Excipients; D011108:Polymers; D013501:Surface-Active Agents; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D012710:Serum Albumin, Bovine; D019344:Lactic Acid; D012967:Sodium Dodecyl Sulfate; D008353:Mannitol; D011092:Polyethylene Glycols