ABSTRACT
Encapsulation of human insulin in lipid vesicular systems such as niosomes was sought as a route to protect this protein against proteolytic enzymes and to improve its oral bioavailability The purpose of this study was to assess the effect of insulin encapsulation in niosomes on oral bioavailability in diabetic rats. Recombinant human insulin was entrapped in multilamellar niosomes composed of polyoxyethylene alkyl ether surfactants [Brij 52 and Brij 92] or sorbitan monostearate [Span 60] and cholesterol. The amount of insulin released in simulated intestinal fluid [SIF] and simulated gastric fluid [SGF] were measured at 37°C. The protection of entrapped insulin against pepsin, a-chymotrypsin and trypsin were evaluated in comparison with free insulin solution. Diabetes was induced by IP injection of streptozotocin [65 mg/kg] in male wistar rats and effects of orally administered niosomes and subcutaneously injected insulin on hypoglycemia and elevation of insulin levels in serum were compared. The extent and rate of insulin release from Brij 92 and Span 60 vesicles were lower than that of Brij 52 niosomes [P<0.05]. Vesicles protected insulin in comparison with free insulin solution against proteolytic enzymes [P<0.05] significantly Animals treated with oral niosome-encapsulated insulin [100 lU/kg] showed decreased levels of blood glucose and elevated serum insulin, which in the case of Brij 92 niosomes, hypoglycemic effect was significant [P<0.05]. Niosomes were also stable in solubilizing bile salt solutions and could effectively prolong the release of insulin in both SGF and SIF. Results of this study showed that niosomes may be utilized as oral carriers of insulin; however, to increase bioavailability of insulin, further studies on the protease inhibitor co-encapsulation in niosomal formulations might be helpful
ABSTRACT
Ketotifen is a benzocycloheptathiophene with a range of pharmacological activities. The present study was carried out to evaluate the action of ketotifen on isolated rat bladder contractions induced by KCl and acetylcholine, compared with the effects of other drugs. Ketotifen [5 micro M] reduced the response to acetylcholine on rat isolated bladder without altering the maximum response and shifted the acetylcholine concentration-response curve to the right 16 - fold. Ketotifen also reduced the KC1response, while atropine only inhibited the response to acetylcholine. Diazoxide inhibited bladder - induced contraction only at high concentration [500 micro M]. This study shows that ketotifen is a relaxant of isolated rat bladder. As the inhibition of contractile overactivity of the bladder is the basis of treatment of bladder instability, provided that a similar effect will be seen in vivo, then ketotifen may have clinical benefits for treatment of this condition