Preparation and in vitro evaluation of thienorphine-loaded PLGA nanoparticles

Poly (d,l-lactic-co-glycolide) nanoparticles (PLGA-NPs) have attracted considerable interest as new delivery vehicles for small molecules, with the potential to overcome issue such as poor drug solubility and cell permeability. However, their negative surface charge decreases bioavailability under oral administration. Recently, cationically modified PLGA-NPs has been introduced as novel carriers for oral delivery. In this study, our aim was to introduce and evaluate the physiochemical characteristics and bioadhesion of positively charged chitosan-coated PLGA-NPs (CS-PLGA-NPs), using thienorphine as a model drug. These results indicated that both CS-PLGA-NPs and PLGA-NPs had a narrow size distribution, averaging less than 130nm. CS-PLGA-NPs was positively charged (+42.1 +/- 0.4mV), exhibiting the cationic nature of chitosan, whereas PLGA-NPs showed a negative surface charge (-2.01 +/- 0.3mV). CS-PLGA-NPs exhibited stronger bioadhesive potency than PLGA-NPs. Furthermore, the transport of thienorphine-CS-PLGA-NPs by Caco-2 cells was higher than thienorphine-PLGA-NPs or thienorphine solution. CS-PLGA-NPs were also found to significantly enhance cellular uptake compared with PLGA-NPs on Caco-2 cells. An evaluation of cytotoxicity showed no increase in toxicity in either kind of nanoparticles during the formulation process. The study proves that CS-PLGA-NPs can be used as a vector in oral drug delivery systems for thienorphine due to its positive surface charge and bioadhesive properties.