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+/-17.9 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).
Wang
Xiaomei
X
Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, China.
Chi
Na
N
Tang
Xing
X
D000281:Administration, Intranasal; D000818:Animals; D001682:Biological Availability; D001921:Brain / Q000378:metabolism*; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers; D004339:Drug Compounding; D004958:Estradiol / Q000008:administration & dosage / Q000097:blood / Q000134:cerebrospinal fluid / Q000737:chemistry / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008297:Male; D053758:Nanoparticles; D009297:Nasal Mucosa / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000097:blood / Q000134:cerebrospinal fluid / Q000737:chemistry / Q000493:pharmacokinetics*; D010316:Particle Size; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar
D004337:Drug Carriers; D018696:Neuroprotective Agents; D004958:Estradiol; D048271:Chitosan