Liposomal Formulations of Serratiopeptidase: In Vitro Studies Using PAMPA and Caco-2 Models

Abstract

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.

Nanoemulsion for improving solubility and permeability of Vitex agnus-castus extract: formulation and in vitro evaluation using PAMPA and Caco-2 approaches

“…PAMPA test is robust and reproducible and relatively fast (4–16 h) (Hiremath et al, 2009 ; Righeschi et al, 2016 ). In the last decades, it resulted as helpful complement and alternative to Caco-2 assay in the pharmaceutical research (Bermejo et al, 2004 ; Kerns et al, 2004 ; Sandhya et al, 2008 ). The experiment was carried out measuring the ability of VAC constituents to diffuse from donor compartment, containing NE formulation, to acceptor compartment, through a PVDF membrane.…”

Serratiopeptidase Niosomal Gel with Potential in Topical Delivery

“…The oral bioavailability of these peptide drugs is generally very low, owing to the acidic conditions of the stomach, proteolytic activity of gastrointestinal tract, and poor permeability across intestinal mucosa. In order to increase the stability of SRP (reduction in acid hydrolysis) and hence to improve bioavailability, various other approaches of delivering the enzymes at the target site have been reported, which include enzyme-entrapped Eudragit S100 microspheres [ 1 ], liposomal formulations of serratiopeptidase [ 2 , 3 ], alginate gel—encapsulated with serratiopeptidase, chitosan-coated ceramic nanocores containing serratiopeptidase [ 4 ], in situ cubic phase transforming system of glyceryl monooleate containing serratiopeptidase [ 5 ], tetracycline-serratiopeptidase-containing periodontal gel [ 6 ], and polar lipid-based lipospheres [ 7 ].…”

A study on blocking store-operated Ca2+ entry in pulmonary arterial smooth muscle cells with xyloketals from marine fungi

“…29. Solutions of xyloketals 1-4 together with the positive controls verapamil, atenolol and ciprofloxacin were added to the wells (100 µL per well) on a pre-coated filter, and phosphate buffer saline (pH 7.4) was added to the wells (375 µL per well) on the receiver plate.…”