Design and characterization of propolis extract loaded self-nano emulsifying drug delivery system as immunostimulant.

This current study aims to optimize, characterize, and observe the stability of the self-nano emulsifying drug delivery system (SNEDDS) of propolis extract (PE) for improving the immune response. Optimization of the selected composition of SNEDDS was conducted using a D-optimal mixture design. SNEDDS was prepared by loading 150 mg/mL of PE in oil, surfactant, and cosurfactant phases. The thermodynamic stability test was carried out with phase separation parameters followed by the robustness to dilution and accelerated stability test. The immunostimulant activity was examined in vitro and in vivo by determining the phagocytic activity, cell proliferation, production of nitrite oxide levels of RAW 264.7 cells, phagocytic activity of macrophages, and the number of leukocytes, neutrophils, and lymphocytes. The formula optimization showed that the formula containing Capryol-90, Cremophor RH40, and PEG 400 at a ratio of 30: 34: 36 was optimum. The verification response of the optimum formula with drug loading showed that the transmittance, droplet size, and zeta potential were 96.90 ± 0.00%, 28.7 ± 1.20 nm, and -56.5 ± 2.05 mV, respectively. The thermodynamic stability test and robustness to dilution did not find any separation phase. The accelerated stability test results were classified as stable. The in vitro and in vivo immunostimulant activity test showed that PE-loaded SNEDDS exhibited a higher immunostimulant effect than PE. In conclusion, the optimum and stable composition of PE loaded SNEDDS was found with a simple and accurate method using the D-Optimal mixture design and demonstrated an immunostimulant activity.

Development of New Indonesian Propolis Extract-Loaded Self-emulsifying: Characterization, Stability and Antibacterial Activity.

Purpose: This study aimed to prepare, characterize, examine the stability and evaluation of the antibacterial activity of Indonesian propolis extract-loaded self-emulsifying (PESE). Methods: Oil, emulsifier, and co-emulsifier were selected as the carrier for the PESE formulation through a propolis-extract solubility test on each carrier, followed by evaluation of the nanoemulsion region in a pseudo ternary phase diagram. Pre-concentrate of PESE was prepared with the addition of 150 mg/mL propolis extract followed by characterization for the transmittance, globule size, zeta potential, thermodynamic stability, robustness to dilution, and accelerated stability. The selected formulation was tested for antibacterial activity using a microdilution method. Results: The PESE characterization produced a clear nanoemulsion with a globule size ranging from 13 to 45 nm and zeta potential of less than -38 mV. The PESE formulation with a composition of 150 mg/mL propolis extract, 20% castor oil, 40%-70% Kolliphor EL, and 10%-40% polyethylene glycol (PEG) 400 were thermodynamically stable. The PESE formulation with the composition of 20% castor oil, 40% Kolliphor EL, and 40% PEG 400 was the optimum formulation that passed the robustness to dilution evaluation and an accelerated stability test for 3 months. The antibacterial activity test on this formulation indicated improved activity against Escherichia coli and Staphylococcus aureus compared with that of propolis extract. Conclusion: These studies demonstrated that PESE in optimum formulation could be used as an antibacterial, particularly in E. coli and S. aureus.