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: Shadab Md, Rashid A Khan, Gulam Mustafa, Krishna Chuttani, Sanjula Baboota, Jasjeet K Sahni, Javed Ali
• Journal: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences (Eur J Pharm Sci) Vol. 48 Issue 3 Pg. 393-405 (Feb 14 2013) ISSN: 1879-0720 [Electronic] Netherlands
• PMID: 23266466 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

• Antiparkinson Agents
• Bromocriptine
• Chitosan
• Sodium Pertechnetate Tc 99m

Topics

• Administration, Intranasal
• Animals
• Antiparkinson Agents (administration & dosage, metabolism, pharmacokinetics, therapeutic use)
• Behavior, Animal (drug effects)
• Blood-Brain Barrier (drug effects)
• Brain (diagnostic imaging, drug effects, metabolism)
• Bromocriptine (administration & dosage, metabolism, pharmacokinetics, therapeutic use)
• Catalepsy (etiology, prevention & control)
• Chitosan (chemistry)
• Disease Models, Animal
• Drug Compounding
• Drug Delivery Systems
• Hypokinesia (etiology, prevention & control)
• Injections, Intravenous
• Male
• Mice
• Nanoparticles (chemistry)
• Neurons (diagnostic imaging, drug effects, metabolism)
• Parkinson Disease (diagnostic imaging, drug therapy, metabolism, physiopathology)
• Radionuclide Imaging
• Random Allocation
• Sodium Pertechnetate Tc 99m
• Tissue Distribution