Effect of Drug Carrier Melting Points on Drug Release of Dexamethasone-Loaded Microspheres

ABSTRACT

Here, we examined the effect of melting point of drug carriers on drug release of dexamethasone (Dex)-loaded microspheres. We prepared poly(L-lactide-ran-ε-caprolactone) (PLC) copolymers with varying compositions of poly(εcaprolactone) (PCL) and poly(L-lactide) (PLLA). As the PLLA content increased, the melting points of PLC copolymers decreased from 61 to 43 ℃. PLC copolymers in vials solubilized at 40–50 ℃ according to the incorporation of PLLA into the PCL segment. Dexamethasone (Dex)-loaded PLC (MCxLy) microspheres were prepared by the oil-in-water (O/W) solvent evaporation/extraction method. The preparation yields were above 70%, and the mean particle size ranged from 30 to 90 µm. The MC(x)L(y) microspheres also showed controllable melting points in the range of 40–60 ℃. Dex-loaded MC(x)L(y) microspheres showed similar in vitro and in vivo sustained release patterns after the initial burst of Dex. The in vitro and in vivo order of the Dex release was MC₈₀L₂₀>MC₉₀L₁₀>MC₉₅L₅, which agreed well with the melting point order of the drug carrier. Using in vivo fluorescence imaging of fluorescein (FI)-loaded microspheres implanted in animals, we confirmed the sustained release of FI over an extended period. In vivo inflammation associated with the PLC microsphere implants was less pronounced than that associated with Poly(lactide-co-glycolide) (PLGA). In conclusion, we successfully demonstrated that it is possible to control Dex release using Dex-loaded MC(x)L(y) microspheres with different melting points.