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
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).
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.
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.
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.
KEY WORDSantibiotics controlled drug delivery fusidic acid PLGA and PHBV microspheres solid-state phase separation
Differential scanning calorimetry
Poly(3-hydroxybutyric acid-co-3-hydroxyvaleric acid)
Poly(L -lactic acid)
Scanning electron microscopy
Glass transition temperature
Enthalpy relaxation temperature
X-ray powder diffraction
Enthalpy of melting
We would like to thank Dr. Tim Smith and Renishaw plc, Wotton-under-Edge, UK for his assistance and the use of the confocal Raman microscope. We also like to thank John Jackson, Kevin Letchford, Sam Gilchrist and Ben Wasserman for their excellent technical assistance and discussion. This work was supported by Canadian Institutes of Health Research (CIHR) New Emerging Team (NET) Grant. In addition, the authors would like to thank Natural Sciences and Engineering Council of Canada (NSERC) for financial support to C.Y. in the form of a NSERC Postgraduate Scholarship-Doctoral (PGS-D).
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