P116 Gastro-resistant microparticles for the oral delivery of Phycocyanin in the Inflammatory Bowel Disease therapy

Abstract Background Inflammatory Bowel Disease (IBD) is a chronically relapsing inflammation of the gastrointestinal tract, with ambiguous etiology. Oral route is the most common and acceptable approach for drug administration in the IBD treatment. However, it remains a challenge to maintain the stability of the drugs during oral treatment, particularly in the gastric environment, due its harsh conditions. In this context, the antioxidant and antiinflagmmatory properties of various natural compounds, as Phycocyanin (PC), a water-soluble bioactive molecule found in algae, can be strongly affected by factors as pH and temperature, inducing PC degradation and attenuating the curative effects. In this work, we produced a gastro-resistant microparticles (MPs) as controlled release systems for PC, and we aimed to compare its efficacy with free PC effects, on rat model of IBD. Methods The novel pharmaceutical system (SPC) was produced by microencapsulation technique, the spray-drying technique, using soy proteins (SPs) as natural excipients, aiming to improve the stability of the active ingredient and to ensure a modified release profile of PC. Rats were divided into groups and colitis was induced by intracolonic instillation of Dinitrobenzene sulfonic acid (DNBS, 20 mg/rat). Effects of preventive oral treatment of free PC or SPC were investigated, bioavailability was assessed and then body weight loss, stool consistency, colon weight/length index, myeloperoxidase activity (MPO), macroscopic damage and disease activity index (DAI) were determined. Results The SPC microparticle systems showed enhanced bioavailability of Phycocyanin, resulting in increased blood concentrations. The SPC system achieved the maximum AUC value and a modified release profile, particularly for gastro-resistant types, with a delayed Tmax of 5 hours, indicating their potential as a gastro-resistant formulation. Both PC and SPC pretreatments significantly ameliorated the severity of DNBS-induced colitis, however SPC pretreatment demonstrated enhanced activity vs PC. SPC rats showed a reduction of DAI, body weight loss and diarrhea incidence >15%, compared to PC (P<0.05); the ability of preventing the DNBS-induced macroscopic colonic damage and the MPO increase in SPC group were significantly higher than PC group (P<0.05) and also a tendency to improvement of colon weight/length index was observed. Conclusion In conclusion, the results of our research demonstrated that gastro-resistant microparticles (SPC) exhibit significantly improved therapeutic efficacy compared to orally administered free PC and can be developed as an effective new oral drug delivery system with controlled release profile in the treatment of IBD.