Application of the “in-oil nanoprecipitation” method in the encapsulation of hydrophilic drugs in PLGA nanoparticles

A novel “in-oil nanoprecipitation” method has been previously developed for the nanoincapsulation of water-soluble drugs in poly (D,L-lactide-co-glicolide) (PLGA) and in the present work it was applied to three hydrophilic model-drugs with different characteristics and molecular weight, namely protamine sulphate, sodium diclofenac and N6-ciclopentiladenosine (CPA). Although the same settings were used for all the model-drugs, the drug loading efficiency resulted higher for the protamine (around 93%), intermediate for diclofenac (around 50%) and very low for the CPA (around 7%), in close dependence on chemical-physical characteristics of the drugs. Also particle size resulted strictly model-drug dependent as well as the drug release rate. In the aim to improve the characteristics of the CPA–loaded nanoparticles, the effects of an additional excipient (lauric acid) or the substitution of PLGA with poly (D,L-lactide) polymer (PLA) was investigated by the evaluation of the in vitro drug release and the drug degradation kinetic in human whole blood. The results indicate that the proposed method seems promising for the nanoencapsulation of hydrophilic drugs in hydrophobic polymers and easily modifiable formolecules difficult to be incorporated into polymeric matrix.