Release modulation of hydrophilic drugs from polymeric nanoparticles produced by in-oil nanoprecipitation process

A novel in oil- nanoprecipitation method using a mixture of cottonseed oil and Tween-80 as non-solvent phase has been developed for the nanoincapsulation of water-soluble drugs in poly(D,L-lactide-coglicolide) (PLGA). In this work the method was applied to three hydrophilic drugs with different structure and molecular weight: i.e. protamine sulphate, sodium diclofenac and N6-ciclopentiladenosine (CPA). The drug- loaded nanoparticles were obtained using the same settings (i.e. type and amount of polymer, percentage of surfactant, oil phase volume) and the same drug / polymer ratios (1:25 and 1: 12.5). The size, the yield and the zeta potential of the particles were found to be dependent on the type of the drug rather than on its amount. The drug loading efficiency was high for the protamine (around 90%), intermediate for diclofenac (around 35%) and relatively low for the CPA (around 4%), in close dependence on chemical-physical characteristics of the probes. To compare the drug release rate from the drug loaded nanoparticles, the time required for the release of 60% of drug was considered. The release rate resulted slow for protamine and diclofenac (from 15 to 24 h) and fast for CPA (around 8 h), according to the drug molecular weight. The ability of a filler (lauric acid) to slow down the drug release rate was highlighted for the CPA –loaded nanoparticles. Finally the CPA degradation kinetic in human whole blood was evaluated comparing CPA-loaded nanoparticles containing the filler with the free drug. The results indicate that the CPA stability in whole blood was increased after nanoincapsulation according to the in vitro profile release pattern. In conclusion, the proposed method appears promising for the nanoincapsulation of the hydrophilic drugs in hydrophobic polymers.