New Insight into the Mechanism of Drug Release from Poly(d,l-lactide) Film by Electron Paramagnetic Resonance.

A novel approach based on convolution of the electron paramagnetic resonance (EPR) spectra was used for quantitative study of the release kinetics of paramagnetic dopants from poly(d,l-lactide) films. A non-monotonic dependence of the release rate on time was reliably recorded. The release regularities were compared with the dynamics of polymer structure changes determined by EPR, SEM, and optic microscopy. The data obtained allow for the conclusion that the main factor governing dopant release is the formation of pores connected with the surface. In contrast, the contribution of the dopant diffusion through the polymer matrix is negligible. The dopant release can be divided into two phases: release through surface pores, which are partially closed with time, and release through pores initially formed inside the polymer matrix due to autocatalytic hydrolysis of the polymer and gradually connected to the surface of the sample. For some time, these processes co-occur. The mathematical model of the release kinetics based on pore formation is presented, describing the kinetics of release of various dopants from the polymer films of different thicknesses.

Performance of DFT methods in the calculation of isotropic and dipolar contributions to 14N hyperfine coupling constants of nitroxide radicals.

In the present study, we tested the widely used density functionals BP86, PBE, OLYP, TPSS, M06-L, B3LYP, PBE0, mPW1PW, B97, BHandHLYP, TPSS0, M06, M06-2X, CAM-B3LYP, ωB97x, and B2PLYP with the cc-pCVQZ basis set in calculations on a set of 23 nitroxide radicals with well-resolved 14N anisotropic hyperfine coupling (HFC) constants. The results were compared with those obtained using the B3LYP/N07D and PBE/N07D methods. The convergence of the HFC values to the complete basis set limit is briefly discussed. The best results were obtained using the M06/COSMO method, with a mean absolute deviation (MAD) of 0.4 G for the dipole-dipole contribution and MAD = 0.6 G for the contact coupling contribution (as compared to 1.1 G and 1.0 G, respectively, for the B3LYP/N07D/COSMO method and 1.7 G and 0.5 G, respectively, for the B3LYP/N07D method). The majority of the functionals yielded satisfactory results for the dipole-dipole contribution, but only the M06 functional yielded similar errors for both the dipole-dipole and isotropic contributions. The RIJCOSX and RI approximations introduced errors equal to or smaller than 0.01 G.