D. Mendeleev University of Chemical Technology of Russia

We present the Raman study of linear oligomers of L-lactide (L-OLA), D,L-lactide (D,L-OLA) and ε-caprolactone (OCL) with the degree of polymerization (DP) varied in the range of 10-100, and their blends. Two Raman methods, which were suggested earlier by our group for neat polylactide (PLA) and copolymers of L-lactide (L-LA) and ε-caprolactone (CL), were extended to analyze the oligomers and their blends. The Raman method of evaluating the crystallinity degree was proven for use for the L-OLA, while Raman method of evaluation of composition of the copolymers was extended to use for blends of the OLA and OCL and blends of PLA and poly(ε-caprolactone) (PCL). For the case of our way of synthesis, the ratios of intensities of the bands of 1,12-dodecanediol (co-initiator of the synthesis) and the bands of OLA can be used as a measure of the DP of the oligomers of up to 40-50. The obtained results can be very useful in development and testing of novel materials for 3D printing, targeted drug delivery systems and tissue-engineering constructions.

The peptide PEN-FFW has emerged as a candidate for hepatocellular carcinoma therapy, with selective efficacy and a favorable safety profile. Development of a suitable formulation has been hindered by its sensitivity to shear and limited physicochemical stability. In this work, we elucidated drug-excipient interactions and exploited them to design a stable nanoassembly. PEN-FFW was encapsulated within a carboxymethyl cellulose-poly(lactide-co-glycolide) core, stabilized by polysorbate 80. Binding and structural features were confirmed by quartz crystal microbalance with dissipation (QCM-D), Fourier transform infrared (FTIR), and dynamic light scattering (DLS), while molecular modeling suggested the formation of a pocket accommodating the peptide within the core. A four-factor, three-level Box-Behnken design was applied to optimize process parameters, yielding a 50 % increase in encapsulation efficiency and enhanced storage stability, as determined by desirability function analysis. The optimized formulation exhibited superior cellular uptake and cytotoxicity in vitro, and in vivo studies in mice demonstrated significantly greater hepatic retention relative to the free peptide.

A novel synthetic route to spirocyclic isoxazolines based on a redox-neutral dearomative cyclization of 3-benzyl-substituted isoxazoline N-oxides has been developed. The reaction likely proceeds through isoxazoline ring opening with generation of an unstable N-oxoiminium cation. The latter acts as an O-electrophile in the cyclization involving the ipso-position of the aryl ring. The reaction exhibits a broad substrate scope and affords spirocyclic isoxazolines featuring novel substitution patterns compared with those accessible by synthetic methods or found in natural sources.