RESUMEN
Chitosan succinate is distinguished by its ability to shield the loaded drug from the acidic environment, localize and keep the drug at the colon site, and release the drug over an extended time at basic pH. The current study attempts to develop polyelectrolyte liposomes (PEL), using chitosan and chitosan succinate (CSSC), as a carrier for liposomal-assisted colon target delivery of 5 fluorouracil (5FU). The central composite design was used to obtain an optimized formulation of 5FU-chitosomes. The chitosan-coated liposomes (chitosomes) were prepared by thin lipid film hydration technique. After that, the optimized formulation was coated with CSSC, which has several carboxylic (COOH) groups that produce an anionic charge that interacts with the cation NH2 in chitosan. The prepared 5FU-chitosomes formulations were evaluated for entrapment efficiency % (EE%), particle size, and in vitro drug release. The optimized 5FU-chitosomes formulation was examined for particle size, zeta potential, in vitro release, and mucoadhesive properties in comparison with the equivalent 5FU-liposomes and 5FU-PEL. The prepared 5FU-chitosomes exhibited high EE%, small particle size, low polydispersity index, and prolonged drug release. PEL significantly limited the drug release at acidic pH due to the deprotonation of carboxylate ions in CSSC, which resulted in strong repulsive forces, significant swelling, and prolonged drug release. According to a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, PEL treatment significantly decreased the viability of HT-29 cells. When compared to 5FU-liposome and 5FU-chitosome, the in vivo pharmacokinetics characteristics of 5FU-PEL significantly (p < 0.05) improved. The findings show that PEL enhances 5FU permeability, which permits high drug concentrations to enter cells and inhibits the growth of colon cancer cells. Based on the current research, PEL may be used as a liposomal-assisted colon-specific delivery.
RESUMEN
BACKGROUND: COVID-19 has been associated with olfactory disturbances in many infected patients. The increase in calcium levels in nasal secretions plays an essential role in the olfactory process with a desensitizing effect on olfactory receptor neurons and negative effects on odor transmission. Calcium chelating agents have the ability to bind calcium in nasal mucus and prevent the negative effects associated with calcium increase. OBJECTIVES: The aim of this work is to demonstrate the intra-nasal topical application of sodium phytate, an environmentally friendly, non-harmful calcium chelating agent, to reduce the adverse effects of calcium on olfactory function and improve olfactory dysfunction according to COVID-19. METHODS: Fifty-two patients with a previous COVID-19 and olfactory dysfunction lasting longer than 90 days were enrolled in a prospective, randomized, blinded, controlled clinical trial. Patients were divided into two equal groups: 26 patients received nasal spray containing 0.9% sodium chloride and 26 patients received nasal spray containing 1% sodium phytate. Olfactory function was measured before treatment and 1 month later using the Sniffin' Sticks test. Calcium content of nasal secretions was determined before and after treatment with an ion-selective electrode. RESULTS: A significant improvement from anosmia to hyposmia was demonstrated after the use of sodium phytate compared with no improvement after the use of sodium chloride. In addition, a decrease in the level of calcium in nasal secretions was observed after the use of sodium phytate. CONCLUSION: Sodium phytate has benefit role on improving the olfactory function after COVID-19.
