Dual encapsulation of hydrophobic and hydrophilic drugs in PLGA nanoparticles by a single-step method: drug delivery and cytotoxicity assays

Dual drug encapsulation in biodegradable nanoparticles is always challenging and often requires strenuous optimization of the synthesis-encapsulation processes. This becomes even more difficult when the simultaneous encapsulation of molecules of different polarity is sought. Here we present a modified emulsification-evaporation process to produce polymeric nanoparticles (NPs) made of the biocompatible and biodegradable polymer poly(lactic-co-glycolic acid) (PLGA) and co-encapsulating simultaneously two different drugs, the hydrophobic dexamethasone (DX) and the hydrophilic diclofenac sodium (DS). Three independent processing parameters were systematically modified to promote the incorporation of the different-polarity drugs into PLGA and to control the particle size under 150 nm. The careful selection of the appropriate solvents (ethyl acetate and methanol) was a key requirement for the successful encapsulation of DX and DS. DS and DX release kinetics as well as cytotoxicity assays underlined the therapeutic potential of the dual encapsulation strategy.