The objective of present study was to develop nonionic surfactant vesicles of proteolytic enzyme serratiopeptidase (SRP) by adapting reverse phase evaporation (REV) technique and to evaluate the viability of SRP niosomal gel in treating the topical inflammation. The feasibility of SRP niosomes by REV method using Span 40 and cholesterol has been successfully demonstrated in this investigation. The entrapment efficiency was found to be influenced by the molar ratio of Span 40？: cholesterol and concentration of SRP in noisome. The developed niosomes were characterized for morphology, particle size, and in vitro release. Niosomal gel was prepared by dispersing xanthan gum into optimized batch of SRP niosomes. Ex vivo permeation and in vivo anti-inflammatory efficacy of gel formulation were evaluated topically. SRP niosomes obtained were round in nanosize range. At Span 40？: cholesterol molar ratio 1？:？1 entrapment efficiency was maximum, that is, 54.82% ± 2.08, and showed consistent release pattern. Furthermore ex vivo skin permeation revealed that there was fourfold increase in a steady state flux when SRP was formulated in niosomes and a significant increase in the permeation of SRP, from SRP niosomal gel containing permeation enhancer. In vivo efficacy studies indicated that SRP niosomal gel had a comparable topical anti-inflammatory activity to that of dicolfenac gel. 1. Introduction Recent advancements in biotechnology and genetic research have led to an increased surge of interest in the use of peptide and protein drugs. However, many of them require special formulation technologies to overcome drug-associated problems such as chemical and physical instability and poor bioavailability. Proteolytic enzymes represent an important class of proteins and peptides with primary pharmacological use as anti-inflammatory and digestive agents. Among this category, serratiopeptidase (SRP) offers a powerful treatment for pain and inflammation with widespread use in arthritis, fibrocystic breast disease, chronic bronchitis, and carpal tunnel syndrome. SRP, an extracellular metalloprotease, is derived from the nonpathogenic enterobacteria Serratia E15. SRP comprises a polypeptide chain of 470 residues and one catalytic zinc ion per molecule with molecular weight 52？kDa. SRP is given orally at a dose of 5–10？mg three times a day. Formulations of SRP are available mainly in the form of enteric coated tablet (Danzen, Takeda Japan). The oral bioavailability of these peptide drugs is generally very low, owing to the acidic conditions of the stomach, proteolytic activity
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