Reproducibility is an important issue in biological characterization of drug candidates

Reproducibility is an important issue in biological characterization of drug candidates and natural products. nanoparticle formation by these lipids. GW843682X While larger nanoparticles (approximately 100 nm) of these GW843682X lipids showed modest macrophage-stimulatory activity smaller nanoparticles (<10 nm) of the same lipids exhibited substantially higher potency. Thus the study revealed an unexpected link between nanoparticle formation and macrophage-stimulatory activity of herb lipids. Although nanoparticles have been extensively analyzed in the context of vehicles for drug delivery our obtaining indicates that drugs themselves can form nanoassemblies and their biological properties may be altered by the way they assemble. ... The difference between the two samples was striking. The ‘90%’ sample showed predominantly large (approximately 100 nm) aggregates as evidenced by AFM and DLS (Figure 2A). On the other hand the ‘100%’ sample showed much smaller (<10 nm) nanoparticles according to AFM and DLS (Figure 2B). Thus these observations indicated that the small lipid nanoparticles were responsible for the MΦ-stimulatory activity. Solvent-dependent formation of nanomaterials has been widely studied in the context of drug delivery vehicle over the last decade (11-16). In addition it has been shown that aggregation of organic molecules could cause promiscuous inhibition of enzymes (17 18 Yet the possibility of nanoparticle formation let alone the biological properties of nanoparticles is hardly considered GW843682X in the studies of herbal natural products. Figure 2 Characterization of ‘90%’ and ‘100%’ samples by AFM and DLS. (A) The ‘90%’ sample showed mostly large BSSG aggregates. (B) The ‘100%’ solution mainly composed of small nanoparticles. The ... In retrospect it is not surprising that a mixture of BSSG and glycolipids forms molecular assemblies in a solvent-dependent manner. When the lipid mixture in 90% MeOH aq. is dried methanol evaporates first and water is left behind in the vial (Figure 3). As a result the polarity of the solution increases as the sample dries. On the other hand when the 100% MeOH solution is dried the solvent polarity remains the same until the end. It is likely that the polar environment encourages the aggregation of hydrophobic lipids and results in GW843682X the formation of large nanoaggregates. On the other hand a less polar environment leads to the formation of smaller nanoparticles. The difference in size can cause differences in the cellular uptake and metabolism which in turn can result in the potency WAF1 difference. Further studies are underway to understand the molecular mechanism of MΦ stimulation by lipid nanoparticles from JTT. Figure 3 Possible solvent effect on lipid aggregation. When the sample solution in 90% methanol aq. is dried methanol is evaporated first leaving a concentrated solution in water. Because of the poor solubility of BSSG in water large aggregates form as the … Conclusion In conclusion the current study revealed that molecular assembly could substantially affect the potency of the MΦ stimulatory lipid mixture. This observation may not be limited to herbal natural products. Rather the current finding points to a possibility that similar nanoassemblies are playing important roles GW843682X in the biological activities of many organic molecules and drugs. Acknowledgments This study was supported by NIGMS/NIH SC3 GM094070 (AK). NIMHD/NIH G12 MD007599-27 which supports the research infrastructure at Hunter College is also acknowledged. A part of AFM study in this work was supported by the U.S. Department of Energy Office of Basic Energy Sciences Division of Materials Sciences and Engineering under Award No. DE-FG-02-01ER45935 (HM). Footnotes Conflict of Interest The authors declare no conflict of.