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

The estradiol(E-2)-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 E-2 CS-NPs suspension was 1.9 mg ml(-1), entrapment efficiency was 64.7% on average. Subsequently, this paper investigated the levels of E-2 in blood and the cerebrospinal fluid (CSF) in rats following intranasal administration of E-2 CS-NPs. E-2-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); t(max) 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); t(max) 28 +/- 17.9min) were significantly higher than those after intravenous administration (29.5 +/- 7.4 ng ml(-1) t(max) 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 E-2 must be directly transported from the nasal cavity into the CSF in rats. Finally, compared with E-2 inclusion complex, CS-NPs improved significantly E-2 being transported into central nervous system (CNS). (C) 2008 Elsevier B.V. All rights reserved.