RESUMEN
Lipid core nanocapsules (NCs) coated with multiple polymer layers were rationally designed as a potential approach for the colonic delivery of camptothecin (CPT). Chitosan (CS), hyaluronic acid (HA) and hypromellose phthalate (HP) were selected as coating materials, to modulate the mucoadhesive and permeability properties of CPT regarding the improvement of local and targeted action in the colon cancer cells. NCs were prepared by emulsification/solvent evaporation method and coated with multiple polymer layers by polyelectrolyte complexation technique. NCs exhibited spherical shape, negative zeta potential, and size ranged from 184 to 252 nm. The high efficiency of CPT incorporation (>94%) was evidenced. The ex vivo permeation assay showed that nanoencapsulation reduced the permeation rate of CPT through the intestinal mucosa by up to 3.5 times, and coating with HA and HP reduced the permeation percentage by 2 times when compared to NCs coated only with CS. The mucoadhesive capacity of NCs was demonstrated in gastric and enteric pH. Nanoencapsulation did not reduce the antiangiogenic activity of CPT and, additionally, it was observed that nanoencapsulation resulted in localized antiangiogenic action of CPT.
Asunto(s)
Quitosano , Nanocápsulas , Nanocápsulas/química , Polímeros/química , Quitosano/química , Camptotecina/farmacología , Camptotecina/química , Lípidos/químicaRESUMEN
The retrogradation of high amylose starch (5% or 10%), by isothermal cycles at 4°C (method 1) or by alternating thermal cycles (method 2) was efficient and promoted important structural modifications. Hydrogels of gellan gum and starch retrograded blends, containing or not ketoprofen, were prepared by ionic and dual cross-linking, at different concentrations of polymer and cross-linkers, and characterized by texture and rheological analysis, X-ray diffraction and morphological analysis. The ionic cross-linking and starch retrograded by method 1 contributed to the improvement of hardness and cohesiveness of hydrogels while the dual cross-linking and starch retrograded by method 2 favored the adhesiveness. The rising of polymer concentration lead to the improvement of all mechanical parameters. Rheological data demonstrated that non-cross-linked dispersions showed a behavior of weak gels and the cross-linked hydrogels presented a predominantly elastic behavior (G'â«Gâ³), peculiar of strong gels. X-ray diffraction, rheological data and the scanning electron microscopy (FEG-SEM) revealed that the increase of polymers and cross-linkers concentration and the presence of drug resulted in stronger and more stable tridimensional structures. The suitable adhesiveness and high strength and elasticity of hydrogels H253IC-KT, H255IC-KT, H21053DC-KT and H21055DC-KT make them more promising materials for the design of mucoadhesive drug delivery systems.
Asunto(s)
Sistemas de Liberación de Medicamentos , Hidrogeles/química , Polisacáridos Bacterianos/química , Almidón/química , ReologíaRESUMEN
CONTEXT: Bioadhesiviness of polyacrylic acid polymers make them promising hydrogels to design topical drug delivery systems, allowing a close contact with biological substrate as well as an enhanced local concentration gradient, both factors that may improve the biological performance of the drugs. AIM: Texture and bioadhesive properties of hydrogels were assessed by using texture analyzer and they were correlated with their rheological behavior and performance as drug delivery systems. METHODS: Aqueous dispersions of both polymers were prepared at 0.5%, 1.0% and 1.5% w/v. Hardness, compressibility, adhesiveness, cohesiveness, bioadhesion, continuous flow, oscillatory dynamic test and in vitro drug release were evaluated. RESULTS: Rheological and texture parameters were dependent on polymer concentration and C974P polymer built the strongest structures. Both 1.5% hydrogels presented high bioadhesion values. About 50% of the metronidazole (MTZ) was sustained released from hydrogels within 2 h with an initial burst release at early stage. After, the release rates were decreased and 10% of the MTZ was released in the next 10 h. The drug release process was driven by Fickian diffusion and complex mechanism for PP and C974P hydrogels, respectively. CONCLUSION: The set of results demonstrated that these hydrogels are promising to be used as topical controlled drug delivery system.