Characterization and anti-inflammatory effects evaluation of chili oleoresin SNEDDS containing capsaicinoids

Abstract

Capsaicinoids are the compounds found in chili plants (Capsicum genus) that confer the pungency to the plant. These have been evaluated due to their anti- inflammatory and analgesic effects as they act directly by binding to Transient receptor potential vanilloid 1 (TRPV1), responsible for the perception and sensation of pain. Transdermal application of these compounds has its side effects as these compounds produce irritation in skin and burning sensation. Therefore, this work is focused on implementing these compounds into self-nanoemulsifying drug delivery systems (SNEDDS) for their potential of enhancing these compounds’ anti-inflammatory properties while reducing its side effects by changing its particle size and its properties. Oleoresins evaluated were obtained from Guajillo chili, Arbol chili and a synthesized oleoresin. Characterization and quantification of capsaicinoids on oleoresins were done by high performance liquid chromatography coupled with diode array detectors (HPLC- DAD) and they were reported as capsaicin equivalents. SNEDDS formulations stability was evaluated after 45 days and they were characterized by their particle size, zeta potential and polydispersity index (PDI) on a Zetasizer. SNEDDS entrapment efficiency (%) was also evaluated by HPLC-DAD. Lastly, in vitro tests were done to indicate anti- inflammatory activity. RAW 264.7 cells were used to determine nitric oxide (NO) inhibition, human dermal fibroblasts (HDFa) were used to evaluate cellular uptake and a fluorescent activity assay kit was used to evaluate COX-2 inhibition. As a result, the major capsaicinoids found were capsaicin and dihydrocapsaicin on Arbol oleoresin and four capsaicin analogues on the synthetic oleoresin. No capsaicinoids were found on Guajillo sample. Average entrapment efficiency was of 91.03%. Formulation stability was determined by PDI values which were lower than 0.500 on all samples and by zeta potential which showed an average of -18.98 mV, indicating formulation stability for both parameters. For cellular assays, RAW 264.7 cells showed no cytotoxicity from these compounds. Higher NO inhibition (%) was shown on SNEDDS formulation with synthetic oleoresin compared to normal oleoresins with an inhibition of 83.1 ± 1.99%. Synthetic oleoresin also showed the highest COX-2 inhibition with an activity of 79.19 ± 1.07%. Despite cellular uptake being higher on oleoresins, nanoemulsions showed a high cellular uptake of 21.18 ± 0.07% on synthetic SNEDDS formulations. This study showed the capability of oleoresins containing capsaicinoids incorporated into SNEDDS as anti- inflammatory agents. This type of formulations has the potential to be applied transdermally in order to be used on treatments for inflammation.