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  • Title: Preparation of estradiol chitosan nanoparticles for improving nasal absorption and brain targeting.
    Author: Wang X, Chi N, Tang X.
    Journal: Eur J Pharm Biopharm; 2008 Nov; 70(3):735-40. PubMed ID: 18684400.
    Abstract:
    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+/-17.9 min) 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).
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