PRONIOSOMES: A VESICULAR DRUG DELIVERY SYSTEM

In the development of new dosage forms, drug delivery using nanotechnology is playing a vital role. Vesicular drug delivery systems have gained wide attention in the field of nanotechnology, such as niosomes, liposomes and proniosomes. Among the vesicular carriers, proniosomes are superior. Proniosomes are water-soluble carrier particles that are coated with surfactant so these are dry formulations. They are rehydrated to use on agitation in hot aqueous media within minutes to form niosomal dispersion immediately. Both hydrophilic and lipophilic drugscan be incorporated into these proteasomes. The physical stability problems of niosomes like aggregation, fusion and leaking are minimized in proniosomes, routes, such as oral, parenteral, dermal and transdermal, ocular, oral mucosal, vaginal, pulmonary, and intranasal. Proniosomes prolong the existence of the drug in the systemic circulation and finally reduces toxicity. This review focuses on different aspects of proniosomes such as preparation, characterization, in vitro drug release, entrapment efficiency, applications in the present scenario in the market and future trends

The Role of a Conserved Serine Residue within Hydrogen Bonding Distance of FAD in Redox Properties and the Modulation of Catalysis by Ca2+/Calmodulin of Constitutive Nitric-oxide Synthases

The crystal structure of the neuronal nitric-oxide synthase (nNOS) NADPH/FAD binding domain indicated that Ser-1176 is within hydrogen bonding distance of Asp-1393 and the O4 atom of FAD and is also near the N5 atom of FAD (3.7Å). This serine residue is conserved in most of the ferredoxin-NADP+ reductase family of proteins and is important in electron transfer. In the present study, the homologous serines of both nNOS (Ser-1176) and endothelial nitric-oxide synthase (eNOS) (Ser-942) were mutated to threonine and alanine. Both substitutions yielded proteins that exhibited decreased rates of electron transfer through the flavin domains, in the presence and absence of Ca2+/CaM, as measured by reduction of potassium ferricyanide and cytochrome c. Rapid kinetics measurements of flavin reduction of all the mutants also showed a decrease in the rate of flavin reduction, in the absence and presence of Ca2+/CaM, as compared with the wild type proteins. The serine to alanine substitution caused both nNOS and eNOS to synthesize NO more slowly; however, the threonine mutants gave equal or slightly higher rates of NO production compared with the wild type enzymes. The midpoint redox potential measurements of all the redox centers revealed that wild type and threonine mutants of both nNOS and eNOS are very similar. However, the redox potentials of the FMN/FMNH· couple for alanine substitutions of both nNOS and eNOS are \u3e100 mV higher than those of wild type proteins and are positive. These data presented here suggest that hydrogen bonding of the hydroxyl group of serine or threonine with the isoalloxazine ring of FAD and with the amino acids in its immediate milieu, particularly nNOS Asp-1393, affects the redox potentials of various flavin states, influencing the rate of electron transfer