Amphiphilic Block Copolymer Microspheres Derived from Castor Oil, Poly(ε-carpolactone), and Poly(ethylene glycol): Preparation, Characterization and Application in Naltrexone Drug Delivery.

In the present study, the newly synthesized castor oil-derived thioether-containing ω-hydroxyacid (TEHA) block copolymers with polycaprolactone (TEHA-b-PCL), with methoxypoly(ethylene glycol) (mPEG), (TEHA-b-mPEG) and with poly(ethylene glycol) (PEG) (TEHA-b-PEG-b-TEHA), were investigated as polymeric carriers for fabrication of naltrexone (NLX)-loaded microspheres by the single emulsion solvent evaporation technique. These microspheres are appropriate for the long-term treatment of opioid/alcohol dependence. Physical properties of the obtained microspheres were characterized in terms of size, morphology, drug loading capacity, and drug release. A scanning electron microscopy study revealed that the desired NLX-loaded uniform microspheres with a mean particle size of 5⁻10 µm were obtained in all cases. The maximum percentage encapsulation efficiency was found to be about 25.9% for the microspheres obtained from the TEHA-b-PEG-b-TEHA copolymer. Differential scanning calorimetry and X-ray diffractometry analysis confirmed the drug entrapment within microspheres in the amorphous state. In vitro dissolution studies revealed that all NLX-loaded formulations had a similar drug release profile: An initial burst release after 24 h, followed by a sustained and slower drug release for up to 50 days. The analysis of the release kinetic data, which were fitted into the Korsmeyer⁻Peppas release model, indicated that diffusion is the main release mechanism of NLX from TEHA-b-PCL and TEHA-b-mPEG microspheres, while microspheres obtained from TEHA-b-PEG-b-TEHA exhibited a drug release closer to an erosion process.