ABSTRACT
The study was aimed to prepare and evaluate gabapentin loaded albumin nanoparticles and to find out their effectiveness in treating epilepsy. Albumin nanoparticles of gabapentin were prepared by pH-coacervation method. The drug was administered into animals as free drug, gabapentin bound with nanoparticles, and gabapentin bound with nanoparticles coated with polysorbate 80. The polysorbate 80 coated nanoparticles increased the gabapentin concentration in the brain about 3 fold in comparison with the free drug. Moreover, the polysorbate 80 coated nanoparticles significantly reduced the duration of all phases of convulsion in both maximal electroshock induced and pentylenetetrazole induced convulsion models in comparison with free drug and drug bound with nanoparticle formulations, which indicates the ability of polysorbate 80 coated nanoparticles to enhance the gabapentin concentration in the brain.
Subject(s)
Amines , Anticonvulsants , Cyclohexanecarboxylic Acids , Drug Carriers , Nanoparticles , Polysorbates , Serum Albumin, Bovine , gamma-Aminobutyric Acid , Amines/administration & dosage , Amines/chemistry , Amines/pharmacokinetics , Animals , Anticonvulsants/administration & dosage , Anticonvulsants/chemistry , Anticonvulsants/pharmacokinetics , Brain/metabolism , Cyclohexanecarboxylic Acids/administration & dosage , Cyclohexanecarboxylic Acids/chemistry , Cyclohexanecarboxylic Acids/pharmacokinetics , Disease Models, Animal , Drug Carriers/administration & dosage , Drug Carriers/chemistry , Drug Carriers/pharmacokinetics , Drug Compounding , Electroshock , Gabapentin , Male , Nanoparticles/administration & dosage , Nanoparticles/chemistry , Pentylenetetrazole , Polysorbates/administration & dosage , Polysorbates/chemistry , Polysorbates/pharmacokinetics , Rats, Wistar , Seizures/drug therapy , Serum Albumin, Bovine/administration & dosage , Serum Albumin, Bovine/chemistry , Serum Albumin, Bovine/pharmacokinetics , gamma-Aminobutyric Acid/administration & dosage , gamma-Aminobutyric Acid/chemistry , gamma-Aminobutyric Acid/pharmacokineticsABSTRACT
Tacrine-loaded chitosan nanoparticles were prepared by spontaneous emulsification. The particle size and zeta potential was determined by scanning probe microscopy and Zetasizer, respectively. The prepared particles showed good drug-loading capacity. The in vitro release studies showed that after the initial burst, all the drug-loaded batches provided a continuous and slow release of the drug. Coating of nanoparticles with Polysorbate 80 slightly reduced the drug release from the nanoparticles. Release kinetics studies showed that the release of drug from nanoparticles was diffusion-controlled, and the mechanism of drug release was Fickian. The biodistribution of these particles after intravenous injection in rats showed that of nanoparticles coated with 1% Polysorbate 80 altered the biodistribution pattern of nanoparticles. FROM THE CLINICAL EDITOR: In this paper, chitosan nanoparticles are investigated in a pre-clinical study as an optimized delivery system for tacrin, a drug with potential significance in Alzheimer's disease. The preparation showed optimal pharmacokinetic characteristics in a rat model.
Subject(s)
Alzheimer Disease/drug therapy , Chitosan/chemistry , Drug Delivery Systems/methods , Nanoparticles/chemistry , Tacrine/administration & dosage , Tacrine/therapeutic use , Animals , Chitosan/administration & dosage , Drug Stability , Injections, Intravenous , Kinetics , Microscopy, Scanning Probe , Nanoparticles/administration & dosage , Particle Size , Rats , Rats, Wistar , Tacrine/pharmacokinetics , Tissue DistributionABSTRACT
Alzheimer's disease (AD) is a progressive degenerative disorder of the brain characterized by a slow, progressive decline in cognitive function and behavior. As the disease advances, persons have a tough time with daily tasks like using the phone, cooking, handling money or driving the car. AD affects 15 million people worldwide and it has been estimated that AD affects 4.5 million Americans. Tacrine is a reversible cholinesterase inhibitor used for treating mild to moderate AD. In the present study, an attempt was made to target the anti-Alzheimer's drug tacrine in the brain by using magnetic chitosan microparticles. The magnetic chitosan microparticles were prepared by emulsion cross-linking. The formulated microparticles were characterized for process yield, drug loading capacity, particle size, in vitro release, release kinetics and magnetite content. The particle size was analyzed by scanning electron microscope. The magnetite content of the microparticles was determined by atomic absorption spectroscopy. For animal testing, the microparticles were injected intravenously after keeping a suitable magnet at the target region. The concentrations of tacrine at the target and non-target organs were analyzed by HPLC. The magnetic chitosan microparticles significantly increased the concentration of tacrine in the brain in comparison with the free drug.
