According to the CDC’s National Center for Health Statistics, more than one-third (36.5%) of U.S. adults are obese. Obesity is the main risk factor for cardiovascular disease and type-2-diabetes. Nutraceuticals such as xanthohumol (XN) have shown potential to inhibit adipogenesis, however, their bioavailability has remained controversial. Hence there is a need to develop targeted therapy, which will increase the concentration of xanthohumol in the adipose tissue. Currently, nanoparticles are used for drug delivery where conventional therapies have proven to be less effective. Among various types of nanoparticles, USPIO have found considerable attention in drug delivery as they are easy to synthesize, inert, and are biocompatible. However, to use them for drug delivery system, the USPIO need to be surface functionalized by ligands such as 3-aminotripropylethoxysilane. The use of 3-APTES provides an amine (–NH2) functional group on the surface of USPIO. Once amine functionalized, the USPIO-NH2 was then conjugated to a XN via dicarboxylic PEG linker (HOOC-PEG-COOH) to yield USPIO-PEG-XN. However, to increase the specificity of the nanoparticles to the white adipose tissue (WAT), a WAT specific peptide, P3 (CKGGRAKDC) will be conjugated onto USPIO-PEG-XN to yield a final product USPIO-PEG-XN-P3. The p3 peptide has been reported to bind specifically to WAT vasculature through the membrane protein prohibitin, hence the presence of P3 onto the nanoparticle will increase the specificity and selectivity of the nanoparticle to the adipose tissue. The presence of amine functional groups on the surface of nanoparticles was confirmed via FTIR and quantified using ninhydrin Assay. The ninhydrin assay revealed the presence of 25mM of amine groups per mg of the USPIO. The amount of XN onto the surface of nanoparticles was quantified using HPLC-UV. The HPLC analysis confirmed the presence of 6.1mg of XN per mg of the USPIO. TEM analysis showed that the USPIO, USPIO-NH2, and USPIO-PEG-XN were all spherical in shape with the average particle size of 20, 25, and 50nm, respectively. The cell viability studies using 3T3 L1 murine adipocyte cell line confirmed that the synthesized USPIO-PEG-XN particles did not induce cytotoxicity. In addition, USPIO-PEG-XN at 3.25mM significantly decreased adipogenesis compared to the XN as measured by decrease in the lipid content using AdipoRedTM lipid quantification assay.

Drug delivery of xanthohumol to adipocytes using ultrasmall superparamagnetic iron oxide nanoparticles

2019 Spring National Meeting

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