Utilization of Nanoparticles in CNS Disorders, Current and Future Perspective: Review
Vishal kumar*
Department of pharmacology, ISF College of Pharmacy Moga, India
Submission:July 21, 2021; Published:September 13, 2021
*Corresponding author: Vishal kumar, Department of pharmacology, ISF College of Pharmacy Moga, Firozpur GT Road Ghal Kalan Moga Punjab, India
How to cite this article: Vishal k. Utilization of Nanoparticles in CNS Disorders, Current and Future Perspective: Review. Glob J Nano. 2021; 5(4): 555670. DOI: 10.19080/GJN.2021.05.555670
Abstract
The field of nanomedicine is growing very fast with the development of different- different nanotechnologies day by day. NPs are able to provide potential benefit in the prevention and diagnosis of various CNS diseases, there is more possibility to develop new therapeutic strategies for completely eradicate the CNS diseases (AD, PD %& ALS) and also for the better diagnosis of CNS disease at earlier stage. Alzheimer’s and Parkinson’ diseases are considered more neurodegenerative diseases worldwide. There is complete understanding of pathology of these diseases are unknown, the current therapy is available only for the neuroprotection and symptom management. Understanding of BBB pathophysiology will provide more specific therapy for the management of CNS diseases. Blood brain barrier (BBB) provides protection of brain, Researchers focuses to develop a novel NPs, carry the drug across the BBB and provide good bioavailability in the brain. Here I review the various neurological disorders and different NPs particularly the applications of NPs in diagnosis and treatment of CNS diseases. Collaboration between researchers, and material scientists is possible to develop a novel therapeutic strategy for the diagnosis sand management of CNS diseases.
Keywords: Nanoparticles; Liposomes; Nano shells; Utilization of Nanoparticles/Nanomaterials in Alzheimer’s; Parkinson’s; Multiple sclerosis
Introduction
Nanomedicine are used now a days in various health departments like oncology, cardiology, and in various types of neurological disorders. This field is growing very fast due to development of various nanotechnologies day by day, in this field nanoparticles and devices are develops on nanometer scale [1,2]. There are number of applications of nanotechnology in central nervous system, including new advancement for the diagnosis of CNS disorders, novel drug delivery methods and the most innovative meth-od for regenerating CNS tissues that will helps in the prevention of occurring new neurological disorder. Nanoparticles are known as innovation of nanotechnology which are used in medicine for the treatment/or prevention and diagnosis of human disease, since NPs dimensions are comparable to biomolecules, such as hemoglobin (~5nm), proteins(~1-20nm), viruses(~20nm), cell membranes(~6-10nm), DNA (with a diameter of ~2nm) [2,3].
Nanomaterials may enter in the body via the various route such as Skin, digestive tract, respiratory tract and via the injections, reached into the body’s various parts and produce their actions (including oxidative stress, DNA damage, cellular apoptosis, inflammatory response). NPs become an essential part of drug delivery research be-cause researcher can deliver optimum dose of impressive medicine throughout the body organs in the form of NPs where it produce controlled, targeted, and sustainable therapeutic effects [4]. World health organization published a data in December 2018 known as the second chief cause of death is stroke worldwide, while seventh is dementia. Dementia categorizes in broad classes, Alzheimer’s and Parkinson disease are the main condition that impairs in human brain. However, form the last decades traumatic brain injury, the autism, schizophrenia, stroke, Alzheimer (apart from depression epilepsy and chronic pain) and Parkinson disease are pathologies are known due to mod-ern neurology research, there is fully functional treatment and cure still unknown [2,5,6].
In the present researcher principally focuses on the characteristics of the Blood Brain Barrier (BBB) and also its permeability for the drugs, the latest strategies for the use of drugs against various CNS disorders conversion of drugs into the nanoparticles to enter the brain so the researchers find out that NPs form of drug is more effective than single drug (Figure 1).
Characterization of various nanoscale devices
An explanation of nanoscale device is necessary for the understanding of their benefits, unique properties, and their limitation; in this article I focuses only on the nanoparticles rather than their types because the types of nanomaterials are described in more details in another articles [2,7].
Liposomes and micelles
It’s a nanoparticle form that widely used now a days because of actual medical application these NPs consist of two major components: surrounding phospholipid bilayer membrane and core material. Aqueous core having a cargo so the water-soluble drug can be carried, while phospholipid bilayer available for the protective coating [8]. Liposomes containing doxorubicin is in clinical use in humans for the ovarian cancer and multiple myeloma has been approved by the US FDA [2,9,10]. Moreover, liposomes as chemotherapy formulation are under investigation for the primary and secondary brain tumors [9]. The hydrophilic outer layer help in the crossing of BBB by the micelles, the one of the major obstacles is to cross the BBB for delivery of nanoparticles in CNS disorders [11].
Nano shells
It is another form of nanoparticle known as nano shells consist of an outer thin met-al shell and a spherical dielectric core is also present in surrounding it. Dimension of the core and shell are designed as that nano shells can either scatter or absorb the light at a specific wavelength [12].
Carbon Nanotubes
Nanotube is another type of nanoparticle, it is made up of single element and has cylindrical shape; this NPs structure having broad range of electrical, thermal, and elastic properties. Carbon is mostly used element for the formulation of nanotubes also known as carbon nanotubes, commonly used in medical application. Carbon nanotubes are the nanostructure made up of graphene sheets, these sheets are converted in cylindrical shapes [13]. The carbon nanotubes was first discovered by the Iijima [14]. Currently it has widely used in the treatment of various neurological dis-orders i.e., ischemic stroke, Alzheimer, and Parkinson [15-17]. However, very poor preclinical studies done for the use of CNTs in neurological disorders.
Gold Nanoparticles
Gold nanoparticles are used for the delivery of drugs against various neurological diseases18.they have various important characteristics like better biocompatibility, simplistic surface functionalization and effective delivery to the diseased cell and tissues [18,19]. Some studies reported by the researcher the Gold NPs are destruct and dissolved Amyloid Beta fibrils and plaques when they used in AD treatment. Principle cause of Alzheimer is formation of plaques and amyloid beta fibrils in the brain which can be destroyed or prevented by the Gold NPs later. Gold NPs are exposed in weak microwave field and interact with fibrils in the brain, dissolve fibrils by the in-creasing temperature. It is shown by the in vitro experiment that Gold NPs slow down the progression of AD [20]. Gao et al. [21] Gold NPs reduces cytotoxicity of amyloid beta mediated peroxidase activity and amyloid beta fibrils having size of 22-nm, Triulzi et al. [22] also reported photo chemical ablation of amyloid beta plaques in AD. Nanobubbles based gold NPs deliver the drug in the brain of AD patient, when the bubbles burst by heating they deliver the drug to target site, based on these results it is a better option of AD disease diagnosis, management and treatment [21,23].
Microparticles
Microparticles are in heterogeneous in nature having small size (0.1-1μm), now a days it is mostly used as a vehicle in drug delivery and Alzheimer disease management, these particles are detected in the cerebrospinal fluid in the CNS [24,25]. It is well known that donepezil drug is approved by the FDA for the cognition and daily life functioning in mild-to-moderate Alzheimer patient, without any changes in the functioning of vital organs, but it has side effect that causes GIT misfunctioning and im-paired memory, this problem has been solved by using PLGA donepezil loaded micro-particles for long term use [26] (Figure 2).
Utilization of NPs/NMs in Various Neurological Disorders
Alzheimer disease
Alzheimer had affected more than 36 million of population worldwide and the cases will be 50million expected by 2050 [27]. At present day Alzheimer management is based on symptoms and vascular prevention by the cholinesterase inhibitors and N-methyl-D-aspartate antagonists. Utilization of nanotechnology and nanoparticles has shown shocking results in AD diagnosis and management. There are various methods are used by the researcher for the production of nanoparticles such as ionic gelation emulsion, polymer polymerization, solvent diffusion, solvent evaporation, spray dying and nanoprecipitation [28]. Researcher focuses the Aβ peptide, tau phosphorylation and metabolic dysfunction for the betterment of Alzheimer treatment. The main cause of AD is hyperphosphorylated neurofibrillary tangles and the formation of amyloid plaques in the brain. some other reasons of AD pathology has been suggested that dysregulation of the cholinergic system [29].
Mainly two classes of medication has been approved for the treatment of Alzheimer, cholinesterase inhibitor (donepezil), galantamine, glutamate antagonist (memantine) and rivastigmine are prescribed by the physician for mild to moderate AD [30]. Improvement of Alzheimer patient’s cognition can be alleviated by the using momantine (MEM) drug. Recently reported that physiochemically stable MEM-PEG-PLGA nanoparticles have been developed by the scientist which is having size smaller than 20nm (12.6±0.5), the negative surface charge is-22.4mV. It was re-ported that the drug is dispersed inside the PLGA matrix and found to be non-cytotoxic in brain cell lines. MEM nanoparticles are tested on transgenic APPsws/PS1dE9 mice and found that they decreased memory impairment as com-pare to free drug solution, it is also confirmed by the histological studies. Tiwari et al. [31] encapsulated curcumin (the main pigment of turmeric) into a highly lipophilic biodegredable nanoparticles and found that it stimulate the adult hippocampal neurogenesis and improved the memory of AD patient [31].
Parkinson disease
Parkinson is a neurodegenerative disease that affects mainly the person whose age is 65 years or above. This disease causes in alteration is body’s natural physiology such as increases body movement, neuronal excitation, body lock. Main cause of PD is degeneration of dopaminergic neurons in area of brain known as substantia nigra (pars compacta). Nanotechnology could be a game changer to alleviate PD. NPs can promote protection and regeneration of affected neurons and enhances the delivery of drug across the BBB. For the betterment of PD treatment extensive research is being conducted and researchers try to develop some new therapeutic strategies for the PD treatment. Peptides and peptide nanoparticles are being used in various CNS disorders not only Parkinson [28].
A recent study prove that the improvement brain targeting of RSG (Rosagiline, a powerful inhibitor of mono amino oxidase type B MAO-B) by the PLGA-NPs (lactide-coglycolide) based nanoparticle coated with chitosan. Principally this study conducted for the delivery and an improvement of bioavailability RSG based nanoformulation in the brain tissue and also for diminish the systemic exposure, it was done on the wistar rat brain, and the plasma shows high P value (P<.005) [32]. In another study it was shown that intracerebroventricular injection of microRNA-124 loaded nanoparticles in mouse model of Parkinson disease, it initiate the enhancement of motor functions [33].
Amyotropic lateral sclerosis
It is another neurodegenerative disease causes the loss of neuromuscular control with fatal outcome. In this disease degeneration of motor neuron occurs in both upper and lower neurons, SODI1 (super-oxide dismutase) and protein inclusion have been found in axons of both neurons. SOD coated gold nanoparticles combined with SODI1 can be used in ALS diagnosis [34].
Multiple Sclerosis
Multiple sclerosis is also a Central nervous system disease, common symptoms are disruption of information flow to the brain and body. It is reported that therapeutic activity increased in inflamed brain of mice using co-polymer of PEG (PCL-PEG) NPs given by intravenously. However, the combination of poly (ethyleneimine) and therapeutic DNA can reduce the disease severity [35,36].
Future Direction
Development of modern and innovative therapeutic strategies for the treatment of CNS disorders can be possible via the utilization of nanotechnology. Nanoparticles represent an identical molecule for the enhancement of performance of nano pharmaceuticals. Assessment of nanoparticles for the symptom management, disease regression and neuroprotection in case of neurological disorders like Alzheimer and Parkinson had done, as discussed in previous sections. Apart from this certain treatment is not available for chronic CNS diseases, collaboration between material scientists, engineers and health care workers is possible to develop a novel therapeutic strategy for the diagnosis and management of CNS disorders.
Conclusion
The well understanding of neurological disorder mechanism has created new opportunity for Nanoparticle technology to eradicate these diseases. Particular NPs have a unique property to cross blood brain barrier, it is difficult to develop a drug that may effectively cross the BBB to reach target site without producing any side effect, and well penetration property Of NPs into the BBB NP-based system enhances the chances of diagnosis/treatment. It is found that various nanoparticles/or nanomaterials had shown significant role in the diagnosis and management of neurological disorders. Stem cell proliferation can be promoted by the using NP. Nanoparticle is the better option for drug delivery in various CNS disorders as compared to conventional mode of therapy, therefore the systemic toxicity study is still required for the application of effective formulation in neurological disorders.
Refrences
- Leary SP, Liu CY, Apuzzo ML (2006) Towards the emergence of neurosurgery part-III nanomedicine targeted nano therapy, progress towards the realization of Neurosurgery 8: 109-126.
- James M Provenzale, Aaron M Mohs (2010) Nanotechnology in Neurology Current Status and Future Possibilities. Nanotechnology in Neurology 6(1): 12-17.
- Riehemann K Schneider, Luger TA, Godin B, Ferrari M, Fuchs H (2009) Nanomedicine-Challenge and perspectives. Angew Chem Int Ed Engl 48(5): 872-897.
- Hans ML, Lowman AM (2002) Biodegradable nanoparticles for drug delivery and targeting. Curr. Opin. Solid State Mater Sci 6(4): 319-327.
- The Top 10 Causes of Death. Available online.
- Lindsley, CW (2014) Global prescription medication statistics: Strong growth and CNS well represented. ACS Chem. Neurosci 6(4):505-506.
- Wiesner MR, Lowry GV, Alvarez P, Biswas P (2006) Assessing the risk of manufactured nanomaterials, Environ Sci Technol 40(14): 4336-4345.
- Vander Meulen DL, Misra P, Michael J (1992) Laser Mediated Release of Dye from Liposomes. Photochem Photobiol 56(3): 325-332.
- Caraglia M, Addeo R, Costanzo R (2006) phase-II study of temozolamide plus pegylated liposomal doxorubicin in the treatment of brain metastases from solid tumors. Cancer Chemother Pharmacol 57: 34-39.
- Rose PG (2005) Pegylated liposomal doxorubicin optimizing the dosing schedule in ovarian cancer. Oncologist 10: 205-214.
- Provenzale JM, Mukundan S, Dewhirst M (2005) The role of blood-brain barrier permeability in brain tumor imaging and therapeutics. AJR Am J Roentgenol 185(3): 763-767.
- Loo C, Lin A, Hirsch L, L Minhoo, Halas N, Drizek R (2004) Nano shell- enabled photonics- based imaging and therapy of cancer. Technol 3(1): 33-40.
- Giugliano M, Prato M, Ballerini L (2008) Nanomaterial/neuronal hybrid system for functional recovery of the CNS. Drug Discov Today Dis Models 5: 37–43.
- Iijima S (1991) Helical microtubules of graphitic carbon. Nature 354: 56-58.
- Kakkar AK, Dahiya N (2015) Management of Parkinson’s disease: current and future pharmacotherapy. Eur J Pharmacol 750: 74-81.
- Folch J, Petrov D, Ettcheto M, Abad S, Sánchez-López E, et al. (2016) Current research therapeutic strategies for Alzheimer’s disease treatment. Neural Plasti 8501693.
- Khwaja Salahuddin Siddiqi, Azamal Husen, Sayed Sartaj Sohrab, Mensur Osman Yassin (2018) Recent Status of Nanomaterial Fabrication and Their Potential Applications in Neurological Disease Management 13(1): 231.
- Siddiqi KS, Husen A (2017) Recent advances in plant-mediated engineered gold nanoparticles and their application in biological system. J Trace Elements Med Biol 40:10-23.
- Husen A (2017) Gold nanoparticles from plant system: synthesis, characterization, and application. In: Nanoscience and Plant–Soil Systems Vol. 48 (Eds. Ghorbanpourn M, Manika K, Varma A) Springer International Publishing AG, Gewerbestrasse 11, 6330 Cham, Switzerland. pp. 455-479.
- Lasagna Reevesa C, Gonzalez Romeroa D, Barriaa MA, Olmedoc I, Closa A, et al. (2010) Bioaccumulation and toxicity of gold nanoparticles after repeated administration in mice. Biochem Biophys Res Commun 393: 649-655.
- Gao N, Sun H, Dong K, Ren J, Qu X (2015) Gold-nanoparticle-based multifunctional amyloid-β inhibitor against Alzheimer’s disease. 2015; Chemistry 21(2): 829-835.
- Triulzi RC, Dai Q, Zou J, Leblanc RM, Gu Q, et al. (2008) Photothermal ablation of amyloid aggregates by gold nanoparticles. Colloids Surf B Biointerf 63(2): 200-208.
- Hadavi D, Poot AA (2016) Biomaterials for the treatment of Alzheimer’s disease. Front Bioeng Biotechnol 4: 49.
- Marzesco AM, Janich P, Wilsch-Bräuninger M, Dubreuil V, Langenfeld K, (2005) Release of extracellular membrane particles carrying the stem cell marker prominin-1 (CD133) from neural progenitors and other epithelial cells. J Cell Sci 118(13): 2849-2858.
- Verderio C, Muzio L, Turola E, Bergami A, Novellino L, et al. (2012) Myeloid microvesicles are a marker and therapeutic target for neuroinflammation. Ann Neurol 72(4): 610-624.
- Zhang J, Atay T, Nurmikko AV (2009) Optical detection of brain cell activity using plasmonic gold nanoparticles. Nano Lett 9(2): 519-524.
- Fonseca Santos B, Gremião MPD, Chorilli M (2015) Nanotechnology-based drug delivery systems for the treatment of Alzheimer’s disease. Int J Nanomedicine 10: 4981-5003.
- Anna PN (2015) Nanotechnology and its applications in medicine. Med Chem 5: 2.
- Anand R, Gill KD, Mahdi AA (2014) Therapeutics of Alzheimer’s disease: past, present, and future. Neuropharmacology 76: 27-50.
- Scheltens P, Kaj Blennow, Monique M B Breteler, Bart de Strooper, Giovanni B Frisoni (2016) Alzheimer’s disease. Lancet 388(10043): 505-517.
- Shashi Kant Tiwari, Swati Agarwal, Brashket Seth, Anuradha Yadav, Saumya Nair (2014) Curcumin-loaded nanoparticles potently induce adult neurogenesis and reverse cognitive deficits in Alzheimer’s disease model via canonical Wnt/beta-catenin pathway. ACS Nano 8(1): 76-103.
- Niyaz A (2017) Rasagiline-encapsulated chitosan-coated PLGA nanoparticles targeted to the brain in the treatment of parkinson’s disease. J. Liquid Chromatogr. Relat. Technol 40(13): 677-690.
- Sofia M Saraiva, Vanessa Castro-López, Covadonga Pañeda, María José Alonso (2017) Synthetic nanocarriers for the delivery of polynucleotides to the eye. Eur. J. Pharm. Sci 103: 5-18.
- Klyachko NL, Haney MJ, Zhao Y, Manickam DS, Mahajan V, et al. (2014) Macrophages offer a paradigm switch for CNS delivery of therapeutic proteins. Nanomedicine (Lond.) 9(9): 403-422.
- Fornaguera C, Solans C (2016) Polymeric nanoparticles for drug delivery in neurological diseases. Curr Pathobiol Rep 4: 189-197.
- Jacobs CB, Ivanov IN, Nguyen MD, Zestos AG, Venton BJ (2014) High temporal resolution measurements of dopamine with carbon nanotube yarn microelectrodes. Anal Chem 86(12): 5721-5727.