Systemic heparin delivery by the pulmonary route using chitosan and glycol chitosan nanoparticles

The aim of this study was to evaluate the performance of chitosan (CS) and glycol chitosan (GCS) nanoparticles containing the surfactant Lipoid S100 for the systemic delivery of low molecular weight heparin (LMWH) upon pulmonary administration. These nanoparticles were prepared in acidic and neutral conditions using the ionotropic gelation technique. The size and zeta potential of the NPs were affected by the pH and also the type of polysaccharide (CS or GCS). The size (between 156 and 385 nm) was smaller and the zeta potential (from +11 mV to +30 mV) higher for CS nanoparticles prepared in acidic conditions. The encapsulation efficiency of LMWH varied between 100% and 43% for the nanoparticles obtained in acidic and neutral conditions, respectively. X-ray photoelectron spectroscopy studies indicated that the surfactant Lipoid S100 was localized on the nanoparticle's surface irrespective of the formulation conditions. In vivo studies showed that systems prepared in acidic conditions did not increase coagulation times when administered to mice by the pulmonary route. In contrast, Lipoid S100-LMWH GCS NPs prepared in neutral conditions showed a pharmacological efficacy. Overall, these results illustrate some promising features of CS-based nanocarriers for pulmonary delivery of LMWH.