RESUMEN
Propolis is a honeybee product that contains a mixture of natural substances with a broad spectrum of biological activities. However, the clinical application of propolis is limited due to the presence of a myriad of constituents with different physicochemical properties, low bioavailability and lack of appropriate formulations. In this study, a modified injection technique (spraying technique) has been developed for the encapsulation of the Egyptian propolis within liposomal formulation. The effects of three variables (lipid molar concentration, drug loading and cholesterol percentage) on the particle size and poly dispersity index (PDI) were studied using response surface methodology and the Box-Behnken design. Response surface diagrams were used to develop an optimized liposomal formulation of the Egyptian propolis. A comparative study between the optimized liposomal formulation prepared either by the typical ethanol injection method (TEIM) or the spraying method in terms of particle size, PDI and the in-vitro anti-proliferative effect against human melanoma cell line A375 was carried out. The spraying method resulted in the formation of smaller propolis-loaded liposomes compared to TEIM (particle sizes of 90 ± 6.2 nm, and 170 ± 14.7 nm, respectively). Furthermore, the IC50 values against A375 cells were found to be 3.04 ± 0.14, 4.5 ± 0.09, and 18.06 ± 0.75 for spray-prepared propolis liposomes (PP-Lip), TEIM PP-Lip, and propolis extract (PE), respectively. The encapsulation of PE into liposomes is expected to improve its cellular uptake by endocytosis. Moreover, smaller and more uniform liposomes obtained by spraying can be expected to achieve higher cellular uptake, as the ratio of liposomes or liposomal aggregates that fall above the capacity of cell membrane to "wrap" them will be minimized.
RESUMEN
The aim of this work was to prepare a combined drug dosage form of famotidine (FAM) and quercetin (QRT) to augment treatment of gastric ulcer. FAM was prepared as freeze-dried floating alginate beads using ion gelation method and then coated with Eudragit RL100 to sustain FAM release. QRT was prepared as solid dispersion with polyvinyl pyrrolidone K30 to improve its solubility. Photo images and scanning electron microscope images of the prepared beads were carried out to detect floating behavior and to reveal surface and core shape of the prepared beads. Anti-ulcerogenic effect and histopathological examination of gastric tissues were carried out to investigate the effect of the combined drug formulation compared with commercial FAM tablets and FAM beads. Gastric glutathione (GSH), superoxide dismutase, catalase, tissue myeloperoxidase, and lipid peroxidation enzyme activities and levels in rat stomach tissues were also determined. Results revealed that spherical beads were formed with an average diameter of 1.64±0.33 mm. They floated immediately with no lag time before floating, and remained buoyant throughout the test period. Treatment with a combination of FAM beads plus QRT showed the absence of any signs of inflammation or hemorrhage, and significantly prevented the indomethacin-induced decrease in GSH levels (P<0.05) with regain of normal GSH gastric tissue levels. Also, there was a significant difference in the decrease of malondialdehyde level compared to FAM commercial tablets or beads alone (P<0.05). The combined formula significantly improved the myeloperoxidase level compared to both the disease control group and commercial FAM tablet-treated group (P<0.05). Formulation of FAM as floating beads in combination with solid dispersion of QRT improved the anti-ulcer activity compared to commercially available tablets, which reveals a promising application for treatment of peptic ulcer.
