RESUMO
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.
RESUMO
The use of synthetic medication for treating alopecia is restricted because of systemic exposure and related negative effects. Beta-sitosterol (ß-ST), a natural chemical, has lately been studied for its potential to promote hair development. The cubosomes with dissolving microneedles (CUBs-MND) created in this study may be a useful starting point for the creation of a sophisticated dermal delivery system for ß-ST. Cubosomes (CUBs) were prepared by the emulsification method, using glyceryl monooleate (GMO) as a lipid polymer. CUBs were loaded with dissolving microneedles (MND) fabricated with HA and a PVP-K90 matrix. An ex vivo skin permeation study and an in vivo hair growth efficacy test of ß-ST were performed with both CUB and CUB-MND. The average particle size of the CUBs was determined to be 173.67 ± 0.52 nm, with a low polydispersity index (0.3) and a high zeta potential value that prevents the aggregate formation of dispersed particles. When compared to CUBs alone, CUBs-MND displayed higher permeating levels of ß-ST at all-time points. In the animals from the CUB-MND group, significant hair development was observed. According to the results of the current investigation, CUBs that integrate dissolving microneedles of ß-ST are superior in terms of transdermal skin penetration and activity for the treatment of alopecia.
RESUMO
BACKGROUND: Antihypertensive drug telmisartan (TEL) belongs to BCS class II, which is characterized by low water solubility and, consequently, low oral bioavailability. Gastroretentive systems may overcome the problems associated with low solubility of TEL and incomplete absorption by localizing the drug release in the stomach. The purpose of this study was to prepare TEL-loaded, oil-entrapped, floating alginate beads with the intent of enhancing the oral bioavailability of TEL for the treatment of hypertension. METHODS: For the formulation and optimization of seventeen formulations of TEL-loaded oil-entrapped floating alginate beads, a central composite design was utilized. The concentration of sodium alginate (X1), the concentration of cross-linker (X2), and the concentration of sesame oil (X3) served as independent variables, whereas the entrapment efficiency (Y1), in vitro buoyancy (Y2), and drug release Q6h (Y3) served as dependent variables. Using the emulsion gelation method and calcium chloride as the cross-linking agent, different formulations of TEL alginate beads were produced. All formulations were evaluated for their entrapment efficiency percentage, in vitro buoyancy, and in vitro drug release. The optimal formulation of TEL alginate beads was prepared with and without oil and evaluated for entrapment efficiency percentage, in vitro buoyancy, swelling ratio, average size, and in vitro drug release. Using scanning electron microscopes, the surface morphology was determined. Using IR spectroscopy, the compatibility between the ingredients was determined. In vivo evaluation of the optimized formulation in comparison to the free TEL was done in hypertension-induced rats, and the systolic blood pressure and all pharmacokinetic parameters were measured. RESULTS: The prepared beads exhibited a high entrapment efficiency percentage, in vitro buoyancy, and prolonged drug release. TEL was compatible with other ingredients, as approved by IR spectroscopy. The prepared TEL beads were spherical, as shown by the SEM. The relative bioavailability of TEL-loaded oil-entrapped beads was 222.52%, which was higher than that of the pure TEL suspension. The prepared TEL beads formulation exhibited a higher antihypertensive effect for a prolonged time compared to pure TEL suspension. CONCLUSIONS: It can be concluded that this innovative delivery method of TEL-loaded oil-entrapped beads is a promising tool for enhancing drug solubility and, thus, oral bioavailability and therapeutic efficacy, resulting in enhanced patient compliance. Furthermore, the in vivo study confirmed the formulation's extended anti-hypertensive activity in animal models.
