Nanotechnology-based drug delivery systems for the treatment of Alzheimer’s disease (original) (raw)
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Expert opinion on drug delivery, 2018
Brain is supposed to be the most complicated part of the body which is very far from the reach of drug moieties. The drug entry in to the brain region depends upon various factors, and among those, the blood-brain-barrier remains the most prominent one. This barrier restricts the entry of almost all the drug and most of the essential biological components like proteins, peptides, etc. and hinders treatment of the CNS disorders. Alzheimer Disease (AD) is one such brain disorder, more specifically a neurodegenerative disorder which primarily affects the older adults. Areas covered: From solubility enhancement to targeted delivery, the nanoparticulate system became the answer for almost all the criticality related to drug delivery. Hence, nanoparticulate drug carrier system has been widely utilizing to remove the hurdles of brain drug delivery. Keeping this in mind, we have underlined the proficiencies of the nanocarrier systems which claim to improve the drug efficacy for the treatmen...
Current and Future Nano-Carrier-Based Approaches in the Treatment of Alzheimer’s Disease
Brain Sciences
It is a very alarming situation for the globe because 55 million humans are estimated to be affected by Alzheimer’s disease (AD) worldwide, and still it is increasing at the rapid speed of 10 million cases per year worldwide. This is an urgent reminder for better research and treatment due to the unavailability of a permanent medication for neurodegenerative disorders like AD. The lack of drugs for neurodegenerative disorder treatment is due to the complexity of the structure of the brain, mainly due to blood–brain barrier, because blood–brain drug molecules must enter the brain compartment. There are several novel and conventional formulation approaches that can be employed for the transportation of drug molecules to the target site in the brain, such as oral, intravenous, gene delivery, surgically implanted intraventricular catheter, nasal and liposomal hydrogels, and repurposing old drugs. A drug’s lipophilicity influences metabolic activity in addition to membrane permeability b...
Delivery of Anti-Alzheimeric Drugs Using Polymeric Nanoparticles -A Review
Alzheimer’s disease (AD) is an elderly cognitive neurodegenerative disorder, characterized by impairment of memory and eventually by disturbances in reasoning, planning, language and perception. This is indicated by senile plaques and neurofibrillary tangles in the brain, which causes defective neurotransmission. The overall increase in the growth of elderly population, due to the wide reach of quality medical care is considered to be major cause for increasing number of AD patients in the society. This review article very specifically outlines the drugs presently used for the treatment of AD and drugs which are currently under research either at pre-clinical or clinical level. Unlike the treatment of other disorders, the presence of blood brain barrier(BBB) possesses a hindrance in transport of drugs from systemic circulation to brain. Nanoparticles in general and particularly polymeric nanoparticles can serve as a potential carrier for delivery of drugs across BBB. A special attention was given to polymeric nanoparticles that were reported to be effective in carrying the AD drug to brain with the polymer used and the method adopted for preparing it.
International Research Journal Of Pharmacy
Objective: Alzheimer's disease is a slowly progressive disease that takes 7 to 10 years from onset to death. Design and development of different lipidbased drug delivery systems (Niosomes) loaded with rivastigmine tartarate is used to solve the problem of the extensive rapid metabolism of rivastigmine. Niosomes as a nanocarriers of rivastigmine will increase its bioavailability and brain targeting. Methods: Niosomes are prepared using Hand Shaking Method (Thin Film Hydration Technique). Span 60 and cholesterol are dissolved in organic mix solvent, until forming clear solution in a round bottom flask. Then, the solvent is evaporated under decreased pressure, temperature and 70 rpm in a rotary evaporator leaving solid surfactant and cholesterol as thin film formed on the wall of the flask. This layer is then rehydrated by using aqueous solution containing drug with continuous shaking which cause swelling of surfactant layer. Swelled amphiphiles eventually fold and form vesicles that could entrap the drug. The Prepared nanoparticles were characterized for pH, particle size, surface morphology, entrapment efficiency and in vitro release study. Results The average particle size was 100.7 nm with polydispersity index of 0.232. The zeta potential of the optimized formulation F2 was determined and found to be-19 mV. Surface properties of the nanoparticles were studied by Transmission electron microscopy (TEM) and nanoparticles found to have smooth surface. The Drug entrapment efficiency was found to be in between 83.5 to 86.53% indicated fairly good drug loading in the formulations indicated increased bioavailability of the drug. optimized formulation F2 showed 60 % drug release in 240 minutes indicate sustained release of drug. Conclusion: Rivastigmine could be prepared as a novel niosomes systems to enhance its bioavailability.
Nanodelivery systems for Alzheimer’s disease: Prospects of natural therapeutic agents
Journal of Applied Pharmaceutical Science
Diseases that cause deterioration of the neurons are many and Alzheimer's disease (AD) is a typical example. The prevalence of AD is increasing with a huge impact on the family, society, and the economy of nations. The central nervous system and its periphery have barriers which are crucial interfaces preventing the entrance of awkward materials. Among these barriers, the blood-brain barrier (BBB) is the most selective and comprises cells coupled with fitted intersections. Nanosized carriers have the prospect for administering drugs to the brain and examples include nanoemulsions, those based on solid lipids and those based on solid and liquid lipids. These formulations can encapsulate active molecules and target necessary transport systems in the brain, thus enabling drug uptake through the BBB. Nanoparticles are of different types and are obtained using diverse techniques and materials. What is common to all nanocarriers is the small sizes and specificity in site targeting. Conventional drugs used in the treatment of AD and bioactive agents can be designed as nanocarriers for improved efficacy. This paper elucidates the use of nanoparticles in managing AD while touching on the prospects of natural therapeutic agents and highlighting future perspectives.
Nanomedicine in the Management of Alzheimer’s Disease: State-of-the-Art
Biomedicines
Alzheimer’s disease (AD) is a deadly, progressive, and irreversible brain condition that impairs cognitive abilities. Globally, it affects 32.6 million individuals, and if no viable therapies are available by 2050, that figure might rise to 139 million. The current course of treatment enhances cognitive abilities and temporarily relieves symptoms, but it does not halt or slow the disease’s development. Additionally, treatments are primarily offered in conventional oral dosage forms, and conventional oral treatments lack brain specialization and cause adverse effects, resulting in poor patient compliance. A potential nanotechnology-based strategy can improve the bioavailability and specificity of the drug targeting in the brain. Furthermore, this review extensively summarizes the applications of nanomedicines for the effective delivery of drugs used in the management of AD. In addition, the clinical progress of nanomedicines in AD is also discussed, and the challenges facing the clin...
International Journal of Nanomedicine, 2021
Current treatments for Alzheimer's disease (AD) attenuate the progression of symptoms and aim to improve the patient's quality of life. Licensed medicines are mostly for oral administration and are limited by the difficulty in crossing the blood-brain barrier (BBB). Here in, the nasal route has been explored as an alternative pathway that allows drugs to be directly delivered to the brain via the nasal cavity. However, clearance mechanisms in the nasal cavity impair the delivery of drugs to the brain and limit their bioavailability. To optimize nose-to-brain delivery, formulations of lipid-based nanosystems, namely nanoemulsions and nanostructured lipid carriers (NLC), formulated in situ gelling hydrogels have been proposed as approaches for nose-to-brain delivery. These formulations possess characteristics that facilitate drug transport directly to the brain, minimizing side effects and maximizing therapeutic benefits. It has been recommended that the manufacture of these drug delivery systems follows the quality by design (QbD) approach based on nasal administration requirements. This review provides an insight into the current knowledge of the AD, highlighting the need for an effective drug delivery to the brain. Considering the mounting interest in the use of nanoemulsions and NLC for nose-to-brain delivery, a description of drug transport pathways in the nasal cavity and the application of these nanosystems and their in situ hydrogels through the intranasal route are presented. Relevant preclinical studies are summarised, and the future prospects for the use of lipid-based nanosystems in the treatment of AD are emphasized.
Targeted nanoparticles for drug delivery through the blood–brain barrier for Alzheimer's disease
Journal of Controlled Release, 2005
Alzheimer's disease (AD) is the most common cause of dementia among the elderly, affecting 5% of Americans over age 65, and 20% over age 80. An excess of senile plaques (h-amyloid protein) and neurofibrillary tangles (tau protein), ventricular enlargement, and cortical atrophy characterizes it. Unfortunately, targeted drug delivery to the central nervous system (CNS), for the therapeutic advancement of neurodegenerative disorders such as Alzheimer's, is complicated by restrictive mechanisms imposed at the blood-brain barrier (BBB). Opsonization by plasma proteins in the systemic circulation is an additional impediment to cerebral drug delivery. This review gives an account of the BBB and discusses the literature on biodegradable polymeric nanoparticles (NPs) with appropriate surface modifications that can deliver drugs of interest beyond the BBB for diagnostic and therapeutic applications in neurological disorders, such as AD. The physicochemical properties of the NPs at different surfactant concentrations, stabilizers, and amyloid-affinity agents could influence the transport mechanism. D
Nanoparticles for therapy of Alzheimer Disease
2013
NAD project (large cooperative; 19 partners, funded by the E.C. , FP72007-2013, G.A. n° 212043) is aiming to the therapy and diagnosis, even combined, of Alzheimer Disease, by creating different multiple-functionalized nanoparticles, able to bind, detect and remove β-amyloid peptide (Aβ) from the brain and from the blood. The results obtained so far show the ability of liposomes functionalized to bind Abeta, to cross the blood-brain barrier either in vitro and in vivo and to reduce the Aβ burden from the brain of transgenic animal models of the disease, thus opening new vistas for the possible therapy of Alzheimer Disease in humans.