How subtle differences in polymer molecular weight affect doxorubicin-loaded PLGA nanoparticles degradation and drug release
Natalya Kumskova, Yu. V. Ermolenko, Nadezhda Osipova, Aleksey Semyonkin, Н. Р. Кильдеева, M. Yu. Gorshkova, Andrey M. Kovalskii, Tatyana Kovshova, Vadim V. Tarasov, Joerg Kreuter, Olga Maksimenko, Svetlana Gelperina
Abstract
Aims: To evaluate the influence of minor differences in molecular weights of commercially available low molecular weight PLGA grades on the kinetics of doxorubicin release from the nanoparticles.Methods: Three low-molecular weight 50/50 PLGA polymers were thoroughly characterised concerning intrinsic viscosity, molecular weight (Mw), acid value, and residual monomer content. The doxorubicin-loaded nanoparticles prepared using these polymers were evaluated concerning the kinetics of drug release and hydrolytic degradation.Results: The Mw of the polymers were slightly different: 10.2, 10.3, and 4.7 kDa. The nanoparticles obtained from the polymer with Mw of 4.7 kDa exhibited considerably higher rates of drug release and polymer degradation.Conclusion: In the case of low molecular weight PLGA grades even a few kilodaltons could be important for the batch-to-batch reproducibility of the nanoformulation parameters. These results bring forward the importance of in-house characterisation of the polymers to be used for the nanoparticle preparation.