title: Bromocriptine loaded chitosan nanoparticles intended for direct nose to brain delivery: pharmacodynamic, pharmacokinetic and scintigraphy study in mice model.
abstract: The primary aim of this study was to investigate the potential use of chitosan nanoparticles as a delivery system to enhance the brain targeting efficiency of bromocriptine (BRC) following intranasal (i.n.) administration. The BRC loaded chitosan nanoparticles (CS NPs) were prepared by ionic gelation of CS with tripolyphosphate anions. These NPs had a mean size (161.3 ± 4. 7 nm), zeta potential (+40.3 ± 2.7 mV), loading capacity (37.8% ± 1.8%) and entrapment efficiency (84.2% ± 3.5%). The oral administration of haloperidol (2mg/kg) to mice produced typical Parkinson (PD) symptoms. Catalepsy and akinesia outcomes in animals receiving BRC either in solution or within CS NPs showed a reversal in catalepsy and akinesia behavior when compared to haloperidol treated mice, this reversal being specially pronounced in mice receiving BRC loaded CS NPs. Biodistribution of BRC formulations in the brain and blood of mice following i.n. and intravenous (i.v.) administration was performed using optimized technetium labeled (99mTc-labeled) BRC formulations. The brain/blood ratio of 0.47 ± 0.04, 0.69 ± 0.031, and 0.05 ± 0.01 for BRC solution (i.n.), BRC loaded CS NPs (i.n.) and (i.v.) respectively, at 0.5h are suggestive of direct nose to brain transport bypassing the blood-brain barrier. Gamma scintigraphy imaging of mice brain following i.v. and i.n. administrations were performed to determine the localization of drug in brain. The drug targeting index and direct transport percentage for BRC loaded CS NPs following i.n. route were 6.3 ± 0.8 and 84.2% ± 1.9%. These encouraging results confirmed the development of a novel non-invasive nose to brain delivery system of BRC for the treatment of PD.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi 110 062, India.
authors.forename: Shadab
authors.initials: S
authors.lastname: Md
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi 110 062, India.
authors.forename: Rashid A
authors.initials: RA
authors.lastname: Khan
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi 110 062, India.
authors.forename: Gulam
authors.initials: G
authors.lastname: Mustafa
authors.affiliation: Department of Radiopharmaceuticals, Institute of Nuclear Medicine and Allied Sciences (INMAS), New Delhi, India.
authors.forename: Krishna
authors.initials: K
authors.lastname: Chuttani
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi 110 062, India.
authors.forename: Sanjula
authors.initials: S
authors.lastname: Baboota
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi 110 062, India.
authors.forename: Jasjeet K
authors.initials: JK
authors.lastname: Sahni
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi 110 062, India. Electronic address: javedaali@yahoo.com.
authors.forename: Javed
authors.initials: J
authors.lastname: Ali
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D001971:Bromocriptine / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use; D002375:Catalepsy / Q000209:etiology / Q000517:prevention & control; D048271:Chitosan / Q000737:chemistry*; D004195:Disease Models, Animal; D004339:Drug Compounding; D016503:Drug Delivery Systems; D018476:Hypokinesia / Q000209:etiology / Q000517:prevention & control; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D009474:Neurons / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D011877:Radionuclide Imaging; D011897:Random Allocation; D013670:Sodium Pertechnetate Tc 99m; D014018:Tissue Distribution
chemical_list: D000978:Antiparkinson Agents; D001971:Bromocriptine; D048271:Chitosan; D013670:Sodium Pertechnetate Tc 99m