Smart PEG-Block-PLA/PLA Nanosystems: Impact of the Characteristics of the Polymer Blend on the Redox Responsiveness

Nanocarriers (NCs) were designed from three polymer blends (B1, B2 and B3) and investigated as smart drug delivery systems (SDDS). The blends are composed of a "smart" copolymer, where methoxy poly(ethylene glycol) and poly(lactic acid) are connected via a redox-responsive disulfide bond (mPEG-SS-PLA), and of a "conventional" polymer, poly(lactic acid) (PLA). They differ by mPEG-SS-PLA/PLA ratio and PLA molecular weight. Nanoprecipitation was used to prepare NCs. Three concentrations were tested, and fluorescent dye Nile red (NR) was used as a model payload. The results show that the characteristics of the NCs, such as size and drug release kinetics, are influenced by the type of blend and the concentration used during the nanoprecipitation process. The more redox-responsive blend was B2 (ratio 1:3, PLA 5 kDa) at 16 mg/mL: the quantity of NR released was tripled upon 24 h of incubation in a reducing medium. This study reveals that the amount of disulfide bonds present in a NC is not the only parameter to be considered to design an SDDS. The stability of the SDDS in a presumably non-stimulating environment is also important to limit uncontrolled release during storage or in the body before the biological target is reached.