Preparation of estradiol chitosan nanoparticles for improving nasal absorption and brain targeting

The estradiol(E2)-loaded chitosan nanoparticles (CS-NPs) were prepared by ionic gelation of chitosan with tripolyphosphate anions (TPP). The CS-NPs had a mean size of (269.3 ± 31.6) nm, a zeta potential of +25.4 mV, and loading capacity of E2 CS-NPs suspension was 1.9 mg ml−1, entrapment efficiency was 64.7% on average. Subsequently, this paper investigated the levels of E2 in blood and the cerebrospinal fluid (CSF) in rats following intranasal administration of E2 CS-NPs. E2-loaded CS-NPs were administered to male Wister rats either intranasally or intravenously at the dose of 0.48 mg kg−1. The plasma levels achieved following intranasal administration (32.7 ± 10.1 ng ml−1; tmax 28 ± 4.5 min) were significantly lower than those after intravenous administration (151.4 ± 28.2 ng ml−1), while CSF concentrations achieved after intranasal administration (76.4 ± 14.0 ng ml−1; tmax 28 ± 17.9 min) were significantly higher than those after intravenous administration (29.5 ± 7.4 ng ml−1tmax 60 min). The drug targeting index (DTI) of nasal route was 3.2, percent of drug targeting (DTP%) was 68.4%. These results showed that the E2 must be directly transported from the nasal cavity into the CSF in rats. Finally, compared with E2 inclusion complex, CS-NPs improved significantly E2 being transported into central nervous system (CNS).