Long term multiple sclerosis drug delivery using dendritic polyglycerol flower-like microspheres

The purpose of this study was to produce and characterize the dendritic polyglycerol microspheres (DPGlyM) carrier with potential for use in the treatment of multiple sclerosis (MS). This novel drug delivery system is comprised of DPGlyM as carrier for dimethyl fumarate (DMF) and curcumin (CUR). Molecular docking (MD) was used as in-silico tool to guide the drug entrapment and indicates a spontaneous interactions of DPGlyM with DMF (ΔG° = -11.3 kJ mol^-1) and CUR (ΔG° = -23.8 kJ mol^-1). The DPGlyM morphology and size distribution were determined using a scanning electron microscopy (SEM). The average size of the microspheres was 30-40 μm. The highest encapsulation efficiency and loading efficiency for CUR and DMF were 94.1% and 65.3%, respectively. The zeta potential indicates that CUR and DMF loaded DPGlyM form stable suspension in phosphate buffer solution (PBS) at pH 7.4. Cytotoxicity and hemocompatibility studies suggest that CUR and DMF loaded DPGlyM not influenced cell viability and are well tolerated in hemolysis assays without any damaging effects even at high concentrations up to 50 mg/mL. The in-vitro release of DMF and CUR in phosphate buffer of pH 7.4 followed a kinetics type super case II transport. The activation energy for CUR and DMF release from DPGlyM was found to be 56.95 kJ/mol and 13.87 kJ/mol for CUR and DMF, respectively. The in vitro release assays show that the DPGlyM has good sustained release of CUR and DMF for 5 days. CUR and DMF loaded DPGlyM have shown promising results for a sustained release during enhanced time duration.