Optimization of a spray drying process to prepare dry powder microparticles containing plasmid nanocomplex.

Successful gene delivery to the lung depends not only on precise and effective design of a nanosized nucleic acid delivery system but also on well engineered liquid or solid microparticles. In present work, we tried to statistically optimize spray dried formulations of low molecular weight chitosan-plasmid nanocomplexes via a D-optimal design with respect to five critical responses: yield of the process, microparticle sizes, nanocomplex sizes, DNA stability and relative transfection efficiency. Nonocomplex formulations prepared by different amounts of solid contents and leucine ratio, and spray dried immediately with varying inlet temperature, feed rate and spray air flow rate. Mean results fitted to 2FI models except for relative transfection efficiency, which fitted in a quadratic model. According to the fitted models, the most important pure factors influencing each response determined to be feed rate for yield and DNA stability, feed fluid concentration for microparticle size, inlet temperature for nanoparticle size and leucine concentration for relative transfection efficiency. However, two-factor interactions have more important roles in microparticle size, nanocomplex size and DNA stability. It was concluded that the optimized formulation could be obtained when all the independent variables were at their maximum tested values, except for feed fluid concentration, which should be in its middle point.

Pharmacokinetic study of niosome-loaded insulin in diabetic rats.

BACKGROUND AND THE PURPOSE OF THE STUDY: 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. METHODS: 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, α-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. RESULTS AND CONCLUSION: 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 IU/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.