|Year : 2020 | Volume
| Issue : 4 | Page : 322-328
Nanoparticle-based dry Powder Inhaler-Based Approach for Corona Virus Disease-2019 Treatment: An Update
Kumar Ajay1, Ashish K Garg2, Sweta Garg3, Shevtank Bhatt4, Neeraj Mishra4
1 Department of Pharmacology, Government Pharmacy Institute, Agam Kuan, Patna, Bihar, India
2 Department of P.G. Studies and Research in Chemistry and Pharmacy, Rani Durgavati University, Jabalpur, India
3 Department of Pharmaceutical Chemistry, Kailash Narayan Patel College of Pharmacy, Bhopal, Madhya Pradesh, India
4 Department of Pharmaceutics, Amity Institute of Pharmacy, Amity University Madhya Pradesh, Gwalior, Madhya Pradesh, India
|Date of Submission||05-May-2020|
|Date of Decision||12-May-2020|
|Date of Acceptance||07-Jul-2020|
|Date of Web Publication||15-Oct-2020|
Dr. Neeraj Mishra
Amity Institute of Pharmacy, Amity University Madhya Pradesh, Maharajpura, Gwalior - 474 005, Madhya Pradesh
Source of Support: None, Conflict of Interest: None
Corona virus disease-2019 (COVID 19) is a respiratory disorder caused by bunches of serious respiratory disorders (i.e., coughing, fever, and breathing problems) like severe acute respiratory syndrome (SARS), and the 79% homology as well as gene sequences are basically similar to SARS-CoV, thus the name of COVID-19 also be distinguish as SARS-CoV-2 on January 7th. Nanoparticles may also improve drug pulmonary efficacy by enhancing residence time, as a consequence the efficient mucus complexation between mucin and nanoparticles caused increment the rate of permeation and tissue uptake and displayed sustainable release property. Advances in device technology have led to the development of more efficient delivery systems capable of delivering larger doses and finer particles into the lung. As more efficient pulmonary delivery devices and sophisticated formulations become available, physicians, and health professionals will have a choice of a wide variety of device and formulation combinations that will target-specific cells or regions of the lung, avoid the lung's clearance mechanisms and be retained within the lung for longer periods. Dry powder inhalers (DPIs) exhibit many unique advantages that have contributed to the incredible growth in the number of DPI pharmaceutical products. To improve the performance, there are a relatively large number of DPI devices available for different inhalable powder formulations. The present review different type of nanoaparticles and DPIs used for the treatment of COVID 19 infections.
Keywords: Corona virus disease-2019, dry powder inhalers, nanoparticles, pulmonary delivery
|How to cite this article:|
Ajay K, Garg AK, Garg S, Bhatt S, Mishra N. Nanoparticle-based dry Powder Inhaler-Based Approach for Corona Virus Disease-2019 Treatment: An Update. Int J Health Allied Sci 2020;9:322-8
|How to cite this URL:|
Ajay K, Garg AK, Garg S, Bhatt S, Mishra N. Nanoparticle-based dry Powder Inhaler-Based Approach for Corona Virus Disease-2019 Treatment: An Update. Int J Health Allied Sci [serial online] 2020 [cited 2020 Dec 3];9:322-8. Available from: https://www.ijhas.in/text.asp?2020/9/4/322/298125
| Introduction|| |
Coronaviruses are a large group of virus infections (i.e., coughing, fever, and breathing problems) that belongs Coronaviridae family. They were named for the crown-like spikes on their surface and were accounted for to cause infections in people and few animal species with a wide range of seriousness. Until this point in time, four fundamental subgroupings of coronaviruses have been recognized named alpha, beta, gamma, and delta. Considered one of the biggest among known RNA infections, the genome size of coronaviruses, which are wrapped with a positive-sense single-abandoned RNA genome and a nucleocapsid of helical balance, ranges from roughly 27–34 kilobases with a width of around 125 nm. The first The first known severe illness in humans caused by a coronavirus emerged in 2003 in China and resulted in the Severe Acute Respiratory Syndrome (SARS) epidemic.
The second episode of serious disease happened in 2012 in Saudi Arabia and prompted the Middle East Respiratory Syndrome (MERS). An epic strain of coronavirus causing serious sickness was as of late revealed in December 2019 in Wuhan, China [Figure 1]. On February 11, 2020, gave the sickness an official name: SARS-CoV-2 or Corona virus disease-2019 (COVID-19). The infection has raised world concern as a result of its high transmission rate just as high versatility and mortality., Individual-to-individual transmission of SARS-CoV-2 is relied on to happen chiefly by means of respiratory beads delivered during hacking, wheezing and talking, and to a great extent looks like the spread of flu., The period among contamination and manifestation beginning may run from 2 to 14 days., Nonetheless, Van Doremalen et al. detailed, under exploratory conditions, that SARS-CoV-2 mist concentrates can stay reasonable for as long as 3 h in pressurized canned products, 4 h on copper, 24 h on cardboard and 2–3 days on plastic and tempered steel. This article will initially survey the proposed regular medications that are presently under broad research and clinical preliminaries. At long last, an uncommon center will be given to the advancement of nanoparticles-based treatment modalities that are anticipated to extensively improve COVID-19 treatment.
|Figure 1: (a) Structure of corona virus disease-2019 (created by Biorander.com); (b) Genomic features of corona virus disease-2019 (N, S and ACE-2 domain); (c) Transmission of severe acute respiratory syndrome-Cov-2|
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Current therapeutic strategies
A couple of ongoing investigations distributed in science give some insight towards understanding what makes SARS-CoV-2 so infective. Aside from understanding the science of the infection, some uncommon advances are expected to limit the disease in the flow situation. SARS-CoV 2, being an RNA infection, can be repressed by drugs recently utilized for other RNA infections, for example, the Human Immunodeficiency Virus (HIV). Furthermore, a mix of medications including chloroquine, a powerful medication used to treat intestinal sickness, has additionally been proposed for clinical utilization. Treatment strategy against COVID-19 illustrate in [Figure 2]. It is estimated that this blend can keep the infection from official to heme. [Table 1] represents the list of companies and their drug/vaccine product formulation against COVID-19. [Figure 3] represents the drug delivery and targeting features via DPI for COVID-19.
|Table 1: Some companies currently developing drugs/vaccines against corona virus disease-2019|
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|Figure 3: Delivery and targeting features of dry powder inhaler for the treatment of Severe Acute Respiratory Syndrome-CoV-2|
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For the advancement of an immunization against SARS-CoV 2, a comparative methodology is getting looked at by Serum Institute of India and Sanofi Pasteur, France. An elective system is added to create antibodies against the spike proteins of the infection, which is being trailed by Moderna Inc., MA, USA. Furthermore, a German Enterprise, CureVac, intends to plan an RNA-based immunization against the infection. In this methodology, RNA that codes for a portion of the viral proteins is brought into the body. This RNA can be utilized to create viral proteins, against which the body would then be able to orchestrate antibodies, therefore getting ready for the infection's assault. Every one of these investigations is under various periods of clinical preliminaries [Table 1]. These antibodies may open up sooner rather than later, however, the time it will take for these to arrive at the market relies on the adequacy and accomplishment in every one of the three periods of clinical preliminaries.
| Proposed Conventional Treatments|| |
As of now, there are no approved antibodies or explicit antiviral medicines for COVID-19. Most medicines right now utilized including cardiovascular/hemodynamic or respiratory are strong, that is, they bolster patients experiencing the infection. To build up an effective treatment for COVID-19, one must see well the system of activity of the infection. Looking like SARS and MERS coronaviruses, this novel SARS-CoV-2 uses a “Lock and Key”system in which the angiotensin changing over compound II goes about as a “key”to enter specific cells holding its “lock.” Additional potential inhibitors to battle COVID-19 incorporate the reciprocal utilization of HIV protease inhibitors, for example, Lopinavir and Ritonavir. Remdesivir is an affirmed HIV turn around transcriptase inhibitor that has indicated wide range exercises against RNA coronaviruses in cell societies and creature models., Holshue. et al. detailed the effective recuperation of a SARS-CoV-2 tainted patient accepting intravenous organization of Remdesivir with no unfriendly occasions. To additionally evaluate its wellbeing and viability, a few stage 3 clinical preliminaries were started in patients with COVID-19 (NCT04292899, NCT04292730, and NCT04252664). A convention including the utilization of Hydroxy-Chloroquine fortified by azithromycin uncovered empowering results for effective treatment of COVID-19., Besides, chloroquine can in a roundabout way act by diminishing the creation of genius fiery cytokines as well as by actuating hostile to SARS-CoV-2 CD8+ T-cells. Cortegiani et al. have as of late inspected the viability and security of chloroquine for the treatment of COVID-19.
| Nanoaprticles Based Dry Powder Inhaler for Covid-19 Treatment|| |
DPIs provide better physicochemical stability and deep lungs deposition using the patient's respiration. In addition, they do not require cold chain storage or reconstitution of powders into solutions for nebulization,, based dry powder inhaler (DPI) with better targeting approach. The growth in NDDS has already boosted the use of DPI for a variety of therapeutic aliments. A lot of novel drug delivery systems have been employed to increase the efficacy of DPI. The development of NDDS based DPIs has the potential to overcome issues associated with carrier as a critical component of the formulation. A particulate-based drug delivery system is a promising alternative approach, which depends on modulating the aerodynamic diameter of drug carriers to circumvent the alveoli macrophage and simultaneously deliver and release the drug into the deep lungs [Figure 3]. Improvement in this lung bioavailability can be attributed to nano-size and lipid vesicular delivery system. Maximum lung deposition and reduced mucus clearance can be achieved by preparing nanoparticles smaller than 500 nm. Furthermore, it was also demonstrated that particle size smaller than 260 nm will bypass the macrophage. Lipophilic and bioadhesive properties of NLC extend residence in the lung while sustained release of the entrapped drug from such lipid matrices prolongs therapeutic effect and inhalation dosing thereby improving patient compliance.
Pulmonary delivery through nanoparticles
Pulmonary delivery of drug has become an attractive target and of tremendous scientific and biomedical interest in the health-care research area as the lung is capable of absorbing pharmaceuticals either for local deposition or for systemic delivery. The respiratory epithelial cells have a prominent role in the regulation of airway tone and the production of airway lining fluid. In this respect, growing attention has been given to the potential of a pulmonary route as a noninvasive administration for systemic and local delivery of therapeutic agents.
In the most recent decade, theranostic nanoparticles have risen as another field of medication joining explicitly focused on treatment dependent on symptomatic devices for the cutting edge treatment of a few ailments. All the more explicitly, broad endeavors have concentrated on the advancement of an NP-based intranasal conveyance framework as a compelling and safe instrument to convey a few remedial moieties (e.g., immunization, drugs, siRNA, peptide, antibodies, and so forth). Critically, NP conveyance frameworks offer various advantages for mucosal organization and incorporate (i) securing the remedial moieties against compound debasement; (ii) broadening their living arrangement and discharge time; (iii) guaranteeing their co-conveyance with adjuvants; (iv) expanding the grouping of conjugated materials in target cells; (v) offering receptor-ligand interceded focusing on conveyance; and (vi) potentiating the invulnerable framework simultaneously. Mucosal treatment is profoundly wanted for irresistible sicknesses since most pathogens start their contaminations at the human mucosal surface. The enormous surface region and rich hair-like plexuses additionally take into account their snappy ingestion. These organization courses have just been evaluated for inoculation against respiratory infections, for example, flu and coronaviruses. A few examinations were performed to distinguish the ideal attributes of the theranostic nanoparticles for aspiratory intranasal organization and were as of late investigated. Novochizol™ nanoparticle vaporized detailing can be utilized to convey and bind any potential enemy of COVID-19 medication to the lungs of intensely sick patients. Bioavanta-Bosti has quite recently finished the improvement of a 48-h Novochizol TM-based assembling procedure to produce intra-pneumonic medication conveyance details appropriate for treating COVID-19 patients. A few sorts of theranostic nanoparticles were proposed as promising for the intranasal organization. They can be partitioned into 3 general classes: organic inorganic, and virus like nanoparticles (VLNP).
| Organic Nanoparticles|| |
Nanoparticles produced using lipids are especially appealing for biomedical applications attributable to their upgraded biocompatibility conferred by the lipid material. Among the different lipid-based definitions adjusted for intranasal conveyance are liposomes, which are round containers having an external phospholipid bilayer and an internal hydrophilic center intended to hold watery restorative operators. Liposomes offer various focal points including an effective embodiment of the conjugated operators and straightforward change to additionally upgrade their mucosal and cell take-up and improve their biocompatibility. Like some other sort of nanoparticles, surface charge assumes a significant job in influencing the pharmacokinetic properties of liposomes. Truth be told, contemplates carried on cationic liposomes following intranasal organization indicated higher assimilation and improved bioavailability contrasted with their contrarily charged partners. This is because of the negative charge of the mucosal layers prompting electrostatic fascination of these decidedly charged nanoparticles just as lessening their freedom by the mucosal cilia.
Polymer-based nanoparticles were accounted for as an alluring conveyance framework basically because of the chance of fitting their properties and capacities to a particular application. Out of the numerous plans of polymer nanoparticles, those made of Chitosan pulled specifically enthusiasm for the intranasal organization because of their nontoxic nature, biocompatibility, biodegradability into nonharmful items in vivo, capacity to open up tight intersections between epithelial cells, and capacity to be handily altered into wanted shapes and sizes.
A dendrimer is radially symmetric atoms with all around characterized, homogeneous, and monodisperse structures. Like Polymer, Dendrimer NP can be synthesized in profoundly stretched 3D systems with a more noteworthy capacity of joining numerous practical gatherings on their surface and typifying nonwater dissolvable, hydrophobic remedial specialists in their center, Chahal et al. created dendrimer NP embodying an antigen-communicating replicon mRNA against deadly exposures to a few fatal pathogens, including Ebola, H1N1 flu, and Toxoplasma gondii pathogens. Nandy et al. detailed the improvement of Poly-L-lysine-based dendrimeric nanoparticles with anionic naphthalene disulfonate surface that can obstruct the passage of HIV infections by an official to the viral envelope protein gp120 and forestalling the development of the CD4-gp120 complex.
Designed inorganic nanoparticles are drawing in exceptional interests because of their capacity to not just go about as ordinary conveyance frameworks to proficiently convey stacked load to target locales, yet in addition to permit improvements responsive qualities and the inherent ability of certain sorts (e.g., Attractive or Gold Nanoparticles) to be checked followingin vivo organization to the human body utilizing noninvasive clinical imaging., Gold nanoparticles can be effectively adjusted and tweaked for intranasal conveyance and can have the benefit of being promptly diffused into lymph hubs accordingly initiating CD8+ (T-executioner) cell-interceded insusceptible reaction., Besides, Gold nanoparticles, inferable from their high nuclear number, can likewise work as astounding exceptionally steady and biocompatible complexity operator for X-beam based clinical imaging, particularly in computed tomography (CT). Silver nanoparticles inward breath conveyance for beginning time treatment of COVID 19 was exhibited by Oron Zachar, 2020. The strategy can serve in medical clinic escalated care units as another standard of care prophylactic treatment for ventilator gained pneumonia.
| Virus-Like and Self-Assembling Protein Nanoparticles|| |
VLNP are circle formed nanoparticles made out of a few particles with sizes extending somewhere in the range of 20 and 200 nm. These nanoparticles result from the self-assembling of proteins got from viral capsids. They were presented as alluring nanomaterials as they don't contain hereditary material yet have the capacity for precisely emulating the genuine infection or antigen as far as structure and antigenic determinant(s). This makes these nanomaterials exceptionally appealing to antigen introducing cells that can be promptly recognized and therefore can trigger an invulnerable reaction. Studies performed following the intranasal conveyance of VLNP got from the flu infection lead to improving the resistance against this infection by activating noteworthy kinds of invulnerable reactions (cell and humoral). Subsequently, they go about as an antibody that can forestall further contaminations (e.g., flu infection) by delivering an essentially high measure of antibodies and T-cells.,,, Self-collecting protein nanoparticles (SAPN) are a novel kind of NP got from the oligomerization of monomeric proteins with a dimeter extending from 20 to 100 nm. Self-get together is characterized as the independent association of particles into a progressively steady structure by utilizing noncovalent holding components to accomplish harmony., Kanekiyo et al. announced the union of SAPN that evoke more extensive and progressively compelling insusceptibility (e.g., 10 times higher hemagglutination restraint immunizer titers) than conventional flu immunizations following intranasal vaccination, and subsequently give a promising stage to create more extensive antibody security against rising infections and different pathogens.,
| Conclusions and Future Perspectives|| |
The exceptionally infectious novel coronavirus SARS-CoV-2 that has contaminated so undeniably in excess of 2.2 million individuals in 210 nations set off an uncommon monetary emergency as an outcome of constrained lockdown to restrain the transmission and put the lives of many tainted individuals at high hazard far and wide. COVID-19 patients are mostly made to do with steady consideration that incorporates cardiovascular/hemodynamic or respiratory methods. While there is as of now no particular treatment for COVID-19, a few medications endorsed for different signs are being researched in clinical preliminaries. These medications depend on the organization of specialists that either obstruct the infection section inside the host cells halting infection replication and contamination of different cells or possibly hinder protease movement (e.g., lopinavir/ritonavir in antiviral medications). A few kinds of theranostic nanoparticles that can be partitioned in 3 general classes natural (e.g., lipid, polymer, dendrimer), inorganic (e.g., gold), and infection like or self-collecting protein nanoparticles, were explored for the intranasal organization. The shape, size and surface charge of the structured nanocarriers are considered as vital elements that ought to be mulled over when advanced for intranasal conveyance and along these lines assume a significant job in the accomplishment of the treatment. Conveyed by means of intranasal route, biocompatible theranostic nanoparticles would thus be able to be an exceptionally encouraging way to deal with a battle against this novel SARSCoV-2 as recently explored against different viral diseases including SARS or MERS coronaviruses utilizing a few methodologies.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]