Barnabas Wilson

Poly(n-butylcyanoacrylate) nanoparticles coated with polysorbate 80 for the targeted delivery of rivastigmine into the brain to treat Alzheimer's disease

Alzheimers disease is a progressive and fatal neurodegenerative disorder manifested by cognitive and memory deterioration, progressive impairment of activities of daily living, and a variety of neuropsychiatric symptoms and behavioral disturbances. Alzheimers disease affects 15 million people worldwide and it has been estimated that Alzheimers disease affects 4.5 million Americans. Rivastigmine is a reversible cholinesterase inhibitor used for the treatment of Alzheimers disease. Central nervous system drug efficacy depends upon the ability of a drug to cross the blood-brain barrier and reach therapeutic concentrations in brain following systemic administration. The clinical failures of most of the potentially effective therapeutics to treat the central nervous system disorders are often not due to a lack of drug potency but rather shortcomings in the method by which the drug is delivered. Hence, considering the importance of treating Alzheimers disease, we made an attempt to target the anti-Alzheimers drug rivastigmine in the brain by using poly(n-butylcyanoacrylate) nanoparticles. The drug was administered as a free drug, bound to nanoparticles and also bound to nanoparticles coated with polysorbate 80. In the brain a significant increase in rivastigmine uptake was observed in the case of poly(n-butylcyanoacrylate) nanoparticles coated with 1% polysorbate 80 compared to the free drug. In conclusion that the present study demonstrates that the brain concentration of intravenously injected rivastigmine can be enhanced over 3.82 fold by binding to poly(n-butylcyanoacrylate) nanoparticles coated with 1% nonionic surfactant polysorbate 80.

Targeted delivery of tacrine into the brain with polysorbate 80-coated poly(n-butylcyanoacrylate) nanoparticles

The purpose of the present study was to investigate the possibility of targeting an anti-Alzheimers drug tacrine in the brain using polymeric nanoparticles. Rats obtained 1mg/kg of tacrine by intravenous injection in the form of three preparations: (1) a simple solution in phosphate buffered saline, (2) bound to poly(n-butylcyanoacrylate) nanoparticles, and (3) bound to poly(n-butylcyanoacrylate) nanoparticles coated with 1% polysorbate 80 (Tween 80). After 1h of post injection the rats were killed by decapitation and tacrine concentration in brain, liver, lungs, spleen and kidneys was analyzed by HPLC. A higher concentration of drug tacrine was observed in liver, spleen and lungs with the nanoparticles in comparison to the free drug. The accumulation of drug tacrine in the liver and spleen was reduced, when nanoparticles were coated with 1% polysorbate 80. In the brain a significant increase in tacrine concentration was observed in the case of poly(n-butylcyanoacrylate) nanoparticles coated with 1% polysorbate 80 compared to the uncoated nanoparticles and the free drug. In conclusion, the present study demonstrates that the brain concentration of intravenously injected tacrine can be enhanced by binding to poly(n-butylcyanoacrylate) nanoparticles, coated with 1% the nonionic surfactant polysorbate 80.

Chitosan nanoparticles as a new delivery system for the anti-Alzheimer drug tacrine

UNLABELLED 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 Alzheimers disease. The preparation showed optimal pharmacokinetic characteristics in a rat model.

Significant delivery of tacrine into the brain using magnetic chitosan microparticles for treating Alzheimer's disease.

Alzheimers 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-Alzheimers 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.

Alzheimer disease and its management: a review.

Alzheimer disease is a progressive degenerative disorder of the brain characterized by a slow, progressive decline in cognitive function and behavior. As the disease advances, persons with Alzheimer disease have tough time with daily usage of things like using the phone, cooking, handling money, or driving the car. The disease is more common in elder population. It is estimated that Alzheimer disease affects 15 million people worldwide and approximately 4 million Americans. The clinical features of Alzheimer disease overlaps with common signs of aging, and other types of dementia, hence the diagnosis remains difficult. The neuropathologic hallmarks of the disorder are amyloid-rich senile plaques, neurofibrillary tangles, and neuronal degeneration. Drugs approved for treating Alzheimer disease include acetylcholinesterase inhibitors and N-methyl-d-aspartate (NMDA) receptor antagonist. Caregivers not getting adequate information about Alzheimer disease may believe that nothing can be done to manage its symptoms. Understanding the extent of Alzheimer disease related knowledge can assist disease management that result in improved disease management and reduced care costs. This article attempts to focus on some of the important recent developments in understanding and management of Alzheimer disease.

Nanoparticles based on albumin: Preparation, characterization and the use for 5-flurouracil delivery

The aim of the study was to formulate and evaluate nanoparticles based on albumin to deliver 5-fluorouracil. The nanoparticles were prepared by coacervation method. The nanoparticles were characterized for particle size, surface charge, size distribution and drug loading capacity. The drug loading capacity varied from 4.22% to 19.8% (w/w). The mean particle size was 141.9 nm and surface charge was -30.3 mV. The drug loaded particles exerted a bi-phasic release pattern with an initial burst effect followed by a sustained release in pH 7.4 phosphate buffer. The drug release was first order diffusion controlled and the mechanism was Fickian. The drug loaded nanoparticles showed superior cytotoxicity when compared to the free drug.

Challenges posed by the scale-up of nanomedicines

The recent cutting-edge developments in nanomedicines have brought numerous advances in the diagnosis and therapy of highly challenging diseases [1]. Nanomedicines, which are medical applications of nanotechnology, are mainly nanoparticle-based drug products. Several comprehensive definitions are now available for nanoparticles in nanomedicine. For pharmaceutical purposes, nanoparticles are colloidal particles that range in size from 10 to 1000 nm (1 μm), they consist of macromolecular materials in which the active principle (drug and/or diagnostic material) is dissolved, entrapped, encapsulated and/or to which the active principle is adsorbed or attached [2,3]. The various types of nanomedicines made are, for example, polymeric nanoparticles, solid lipid nanoparticles, liposomes, dendrimers, polymeric micelles and carbon nanotubes [2]. The US FDA-approved nanomedicine products, such as Doxil (Janssen Products, LP, PA, USA) and Abraxane (Celgene Corporation, NJ, USA), are typical examples of the outcome of aggressive research on nanomedicines, and available in the market for the treatment of ovarian cancer and metastatic breast cancer, respectively [4]. However, nanomedicines still impose many challenges to researchers to obtain the maximum benefits for patients during diagnosis and therapy [5]. The launch of new nanomedicine products on the market is preceded by different developmental stages. A forthcoming major challenge among the developmental stages of nano medicine is industrial scale-up (large scale industrial production). It is well known that nano medicine preparations in the laboratory scale are achievable and well documented by

Multifunctional radionanomedicine: a novel nanoplatform for cancer imaging and therapy

Cancer is the second leading cause for death worldwide, highlighting the paramount importance of cancer research. Decades of research has led to many innovative improvements in cancer research, especially in the areas of imaging and therapy [1]. But the fact is that cancer still it remains a chronic and debilitating disease. Despite these concerns, the cutting edge technologies of nanomedicine provide tremendous scope for treating cancer. Recently, the focuses of the emerging nanomedicine field have been to develop multifunctional nanoplatforms that combine both diagnostic/imaging and therapeutic aspects [1–3]. This type of ‘theranostic’ plays a major role for effective cancer imaging and therapy [4,5]. Radiolabeled nanomedicine (nanoparticles) can be termed as ‘radionanomedicine’, which is effective in the treatment of cancer. It can be also used for theranostic purposes with appropriate radionuclides [4,6]. The most important advantage of radionanoparticles is that they do not alter the original characteristics of the entrapped drug molecule/radionuclide. Multifunctional/theranostic radionanomedicines are able to deliver the radionuclide in a targeted manner to cancer cells, to improve the efficacy and safety of both cancer imaging and therapy with the help of a cancertargeting ligand [1]. Indeed, the development of multifunctional/theranostic radionanomedicine is become a possible state-of-the-art in nanomedicine research [5,6]. Liposomes, dendrimers, quantum dots, iron oxide, nanomicelles, perflurocarbon and carbon nanotubes are commonly used carriers for the fabrication of radionanomedicines. The addition of multifunctional/theranostic approaches into these radionanomedicine carriers can make earlier detection and better treatment of cancer possible [7]. Various radionanomedicines have been demonstrated for multifunctional/ theranostic approaches in preclinical animal studies. Clinical and nanotoxicological studies are required to translate these novel platforms, which have potential clinical benefits for cancer patients [7]. This editorial will focus on recent advances in the design of multifunctional radionanomedicine and its future perspectives.

Brain targeting PBCA nanoparticles and the blood–brain barrier

The brain is quite unique from other organs of the body. Despite enormous advances in brain research, CNS brain disorders still remain accountable for a high number of hospitalizations requiring prolonged care. It is estimated that approximately 1.5 billion people worldwide are suffering from various CNS disorders, such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, multiple sclerosis, HIV-dementia and stroke, among others. In recent years, the explosion of interest in the biological aspects of CNS disorders as well as the brain has led to an improvement in the understanding and the treatment of these diseases; however, they still remain chronic and debilitating disorders for many patients. As demographic trends show an increase in the percentage of elderly people in the population, diseases of the brain are becoming a major health problem. It is expected that the number of cases of CNS diseases will be around 1.9 billion by 2020 [1]. Despite these challenges, brain drug targeting plays a vital role and gives tremendous hope for the treatment of these disorders. This area of study is fascinating as well as challenging to the scientists who are in this domain.

Albumin nanoparticles for the delivery of gabapentin: Preparation, characterization and pharmacodynamic studies

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.