RESUMEN
We report here on the synthesis, characterization, degradation, and drug release of acetal-protected gluconic acid-based poly(α-hydroxy ester). This polyester was synthesized by ring-opening polymerization of O-carboxyanhydride of acetal-protected gluconic acid. The polymer undergoes hydrolytic degradation under mild acidic media, whereas minimal degradation takes place under physiological pH. Under acidic conditions, the acetal-protecting groups are hydrolyzed, resulting in a water-soluble polyester with saccharide side chains that erodes from the surface, leaving the bulk of the polymer matrix intact. At pH 3.5, zero-order kinetics was maintained for 50 days accounting for â¼75% drug release. These biodegradable, pH-responsive, sustained zero-order release kinetics of the polymer have application as drug carriers for oral drug delivery or medical implants or also for nonmedical applications.
Asunto(s)
Proliferación Celular , Dexametasona/química , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos , Gluconatos/química , Hidrogeles/química , Polímeros/química , Animales , Dexametasona/farmacología , Liberación de Fármacos , Concentración de Iones de Hidrógeno , Ratones , Células 3T3 NIH , PolietilenglicolesRESUMEN
Newly synthesized acylethanolamide derivatives oleoyl-L-valinolamide (1), oleoyl-D-valinolamide (2), elaidoyl-L-valinolamide (3), elaidoyl-D-valinolamide (4) stearoyl-L-valinolamide (5), and palmitoyl-L-valinolamide (6) were investigated in mice as antiobesity compounds. Compounds 1, 2, 5, 6 significantly decreased body weight by 6.57% following eight injections of 1 mg/kg i.p. during 39 days, while 3 and 4 showed no such activity. Receptor binding indicated that no compound activated CB1, CB2, PPARα, or TRPV1 receptors. Hypothalamic RT-PCR showed that mRNA expression of the anorexigenic genes POMC and CART was up-regulated by 1, 2, 5 and 1, 2, respectively, while that of the orexigenic genes NPY and CaMKK2 was down-regulated by the respective compounds 1, 5, 6 and 1, 2, 5. Oleoyl-L-valinolamide enhances anorectic pathways and lead to decreased glucose levels, enhanced locomotor activity, and improved cognition. Effects of oleoyl-L-valinolamide on weight were dose-dependent, and it could be given orally. 1, 2, 4, 5 down-regulated FAAH mRNA expression.