PLGA and PHBV microsphere formulations and solid-state characterization: possible implications for local delivery of fusidic acid for the treatment and prevention of orthopaedic infections.
OBJECTIVE
To develop and characterize the solid-state properties of poly(DL-lactic-co-glycolic acid) (PLGA) and poly(3-hydroxybutyric acid-co-3-hydroxyvaleric acid) (PHBV) microspheres for the localized and controlled release of fusidic acid (FA).


METHODS
The effects of FA loading and polymer composition on the mean diameter, encapsulation efficiency and FA released from the microspheres were determined. The solid-state and phase separation properties of the microspheres were characterized using DSC, XRPD, Raman spectroscopy, SEM, laser confocal and real time recording of single microspheres formation.


RESULTS
Above a loading of 1% (w/w) FA phase separated from PLGA polymer and formed distinct spherical FA-rich amorphous microdomains throughout the PLGA microsphere. For FA-loaded PLGA microspheres, encapsulation efficiency and cumulative release increased with initial drug loading. Similarly, cumulative release from FA-loaded PHBV microspheres was increased by FA loading. After the initial burst release, FA was released from PLGA microspheres much slower compared to PHBV microspheres.


CONCLUSIONS
A unique phase separation phenomenon of FA in PLGA but not in PHBV polymers was observed, driven by coalescence of liquid microdroplets of a DCM-FA-rich phase in the forming microsphere.
Yang
Chiming
C
Faculty of Pharmaceutical Sciences, The University of British Columbia, 2146 East Mall, Vancouver BCV6T1Z3, Canada.
Plackett
David
D
Needham
David
D
Burt
Helen M
HM
D000900:Anti-Bacterial Agents / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D003692:Delayed-Action Preparations / Q000737:chemistry*; D005672:Fusidic Acid / Q000737:chemistry*; D006016:Glycolates / Q000737:chemistry*; D007700:Kinetics; D019344:Lactic Acid; D008863:Microspheres; D010316:Particle Size; D044367:Phase Transition; D011091:Polyesters / Q000737:chemistry*; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D033362:Powder Diffraction; D013499:Surface Properties; D014961:X-Ray Diffraction; D000094122:Polyhydroxybutyrates
D000900:Anti-Bacterial Agents; D003692:Delayed-Action Preparations; D005672:Fusidic Acid; D006016:Glycolates; D019344:Lactic Acid; D011091:Polyesters; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; C052620:poly(3-hydroxybutyrate)-co-(3-hydroxyvalerate); D000094122:Polyhydroxybutyrates