title: Formulation of sustained-release microspheres of granulocyte macrophage colony stimulating factor by freezing-induced phase separation with dextran and encapsulation with blended polymers.
abstract: This study aimed to assess the potential merits of formulating sustained-release microspheres of recombinant human granulocyte macrophage colony stimulating factor (rhGM-CSF) via freezing-induced phase separation (FIPS) of the protein with dextran followed by encapsulation with binary mixture of poly(lactic-co-glycolic acid) (PLGA) 2A (MW∼12K) and 3A (MW∼47K) or of PLGA2A and polylactic acid (PLA; MW∼83K). The formulated dextran particles and microspheres were characterized in vitro for loading, aggregation, bioactivity and release behavior of the protein where appropriate. rhGM-CSF retained about 60% of bioactivity with no significant aggregation after each formulation step. Encapsulation of protein-loaded dextran particles attained only 80% with the PLGA2A and PLGA3A blend, but 100% with the PLGA2A and PLA mixture. The former formulation exhibited a triphasic in-vitro release profile typical of PLGA microspheres while the latter revealed a much lower initial burst followed by a steady and complete release of rhGM-CSF with preserved bioactivity over a 15-day period.
authors.affiliation: School of Pharmacy, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Xin-ran
authors.initials: XR
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Zheng
authors.forename: Tuo
authors.initials: T
authors.lastname: Jin
authors.forename: Albert H L
authors.initials: AH
authors.lastname: Chow
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000737:chemistry*; D003911:Dextrans / Q000737:chemistry*; D005615:Freezing; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D008863:Microspheres; D044367:Phase Transition; D011091:Polyesters; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D003692:Delayed-Action Preparations; D003911:Dextrans; D011091:Polyesters; D011108:Polymers; D011994:Recombinant Proteins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide); D016178:Granulocyte-Macrophage Colony-Stimulating Factor