Liposomal formulations of serratiopeptidase: in vitro studies using PAMPA and Caco-2 models.

The feasibility of using liposomes as a potential oral delivery system for the systemic delivery of other peptides and protein-based pharmaceuticals has been studied. Serratiopeptidase, a proteolytic enzyme, was used as a model drug. Liposomes were prepared by a thin film hydration method using various lipids, namely, soya lecithin, DMPC and DMPE. It was further investigated whether the liposomal formulations of serratiopeptidase altered the permeability/absorption of the drug using PAMPA, a non-cell-based assay, and Caco-2 assay, a cell monolayer system, mimicking in vivo GI epithelium cells. The entrapment efficiency of the formulations was found to be 62%, 84% and 86% for the liposomes of soya lecithin, DMPC and DMPE respectively. The effectiveness of the liposomal formulations against the pure drug in terms of permeability/absorption was compared. The effective permeability (log Pe) values from PAMPA study varied from -7.47 to -6.5 cm/s whereas for the serratiopeptidase it was -7.72 cm/s. The apparent permeability values calculated from Caco-2 assay varied from 1.25 x 10(-6) to 1.61 x 10(-6) cm/s whereas for the serratiopeptidase it was 1.25 x 10(-6) cm/s. The flux was found to be 3.88-4.96 microg/cm (2)/h for the formulations when compared to 3.208 microg/cm(2)/h for serratiopeptidase. The results obtained indicated that in comparison with the pure drug, incorporation of drug into liposomes improved the permeability. Thus it could be concluded that the liposomal formulations would improve the oral absorption of serratiopeptidase.

Niosomal methotrexate gel in the treatment of localized psoriasis: phase I and phase II studies.

BACKGROUND: Efficacy of topical methotrexate in psoriasis is limited by its penetration. AIMS: The study involved the preparation of niosomal methotrexate in chitosan gel and to test the same for irritation and sensitization on healthy human volunteers followed by assessing the efficacy of the gel through double-blind placebo-controlled study on psoriasis patients and also comparing its efficacy with a marketed methotrexate gel. METHODS: The methotrexate niosomes were prepared by lipid layer hydration method. The characterized niosomes were incorporated in chitosan gel. The gels were tested on 10 human volunteers to check for irritation and skin sensitivity by human repeated insult patch test (HRIPT). The formulations were assessed for efficacy by double-blind placebo-controlled study in 10 psoriasis patients for each formulation. The efficacy was calculated by psoriasis area and severity index scoring method. The global score was used to assess the progress of the disease. RESULTS: The HRIPT test did not produce any significant irritation or sensitization on healthy human volunteers. The placebo and marketed gels were compared with niosomal methotrexate gel. At Week 12, with niosomal methotrexate gel, there was reduction in total score from 6.2378+/-1.4857 to 2.0023+/-0.1371. CONCLUSION: These results suggest that niosomal methotrexate gel is more efficacious than placebo and marketed methotrexate gel.