Modifying the aggregation state may improve the activity of Ozempic

We here report a study of aggregation of Semaglutide at different temperatures, using resonance light scattering (RLS), fluorescence polarization and back-scattering techniques. Fluorescence emission spectra were obtained by exciting the samples at 275 nm and 295 nm, revealing a peak emission at 600 nm associated with the aggregation process. The size of the aggregates is around 100 nm according to back-scattering measurements. Two distinct thermal transitions were observed by RLS: the first melting point (Tm1) at 30{degrees}C and the second (Tm2) at 91{degrees}C, indicating changes in aggregation state. The fluorescence polarization revealed a fast rotational dynamics of the aggregates at Tm2, leading to greater depolarization of the emitted light. The structural organization of the Ozempic aggregates was studied using two dyes, Laurdan for lipid components and 1,8-ANS for protein component (GLP1). Thus, revealing a stable PEG-lipid core which hold the GLP1, increasing their exposition to the solvent. An enhanced FRET event inside the aggregates in presence of Fe2+ and Fe3+ was observed. We conclude that the PEG-lipid core plays a significant role in the aggregates structure stability, being a key to improve the biological activity of Ozempic. This methodology can be used to study similar aggregation constructs in the pharmaceutical industry.