Department of Pharmaceutics /Ashokrao Mane college of Pharmacy, Peth Vadgaon, Shivaji university 416112, Maharashtra, India.
The cause of severe acute respiratory syndrome (SARS) is the SARS coronavirus (SARS-CoV), a viral respiratory disease that manifests as fever, coughing, dyspnoea, and pneumonia. Being near a confirmed or suspected case, or visiting a person who is affected, and by using laboratory techniques like RT-PCR or serology to find SARS-CoV RNA or antibodies They can be treated with a variety of medications, including oxygen therapy, immunomodulators, and bronchodilators. However, there are still certain issues with medication side effects and efficacy. Targeted therapeutics and accurate medication distribution methods are essential to therapy of various disorders in order to maximise therapeutic success while minimising systemic side effects. The function of drug delivery system in severe acute respiratory illness is main topic of this comprehensive review. In particular, new biologicals, Inhaled corticosteroids and gene therapy, Personalized medicine and drug delivery methods based on nanoparticles are all reviewed. We hope to offer comprehensive overview of the existing situation & potential upcoming developments for enhancing treatment leads to these challenging conditions through looking at the latest advancements & approaches within these fields.
In March 2003, The World Health Organisation (WHO) within China's Province of Guangdong. recognised One new and quickly spreading respiratory condition known as SARS (severe acute respiratory syndrome) as a global risk. Over the ensuing months, SARS expanded to more than 30 nations worldwide, becoming the first pandemic of the twenty-first century. It demonstrated how the period of globalisation and greater worldwide travel could significantly boost the spread of an infectious microorganism. Several new viruses, such as Hantavirus, Nipah virus, H5N1 influenza, and avian flu emerged in the ten years before the SARS pandemic. SARS, however, stood out from the others due to its capacity for effective transmission between individuals [1]. By July 2003, when the epidemic was over, 8096 cases had been reported, resulting in 774 deaths, or an overall fatality rate of more than 9.6% [2] [3]. Healthcare professionals exhibited a distinct preference for SARS, accounting for 21% of cases [4]. Three antigenic categories can be distinguished among the coronaviruses of the coronavirus genus. HCV-229E, or human coronavirus 229E, pig the feline infectious peritonitis virus (FIPV) and the epidemic diarrhoea virus make up first group. OC34 (HCoV-OC43) human coronavirus, bovine coronavirus, and murine hepatitis virus are all members of group 2. Infectious bronchitis virus in birds is found in group 3. Despite being a recent addition to the genus Coronavirus, SARS-CoV does not fit into any of the three antigenic groups; yet, some reports indicate that it most closely resembles the group 2 coronavirus [5]. SARS-CoV may have originated in animals. SARS-CoV–like virus with >99% nucleotide homology with human SARS-CoV was identified in Animals from Guangdong, China's live animal marketplaces, include palm civets [6]. Positive-sense single-stranded RNA viruses are known as CoVs. with helical nucleocapsids that vary in size from 80 to 160 nm. They get their name from their crown-like appearance. Since they possess the biggest known genome of RNA and are members of the family Coronaviridae within the Nidovirales order, there is a greater chance of genetic diversity [7][8].
SARS-Cov Is a Novel Virus with Animal Origins, As Evidenced By
Pathophysiology of SARS
The ACE2, or angiotensin-converting enzyme 2, receptor is, how the SARS-CoV, or SARS coronavirus enters its host [10]. SARS-CoV uses its binding domain for receptors to identify The host receptor for ACE2. This and other coronaviruses may be able to generate more and new cross-species infections if this domain is mutated [11]. Because the lungs and small intestine have a high density of its receptors, the virus concentrates there [10]. In particular, the highest infection focus is seen in the alveolar epithelium [10]. The infection causes consolidations, pulmonary oedema, and serous pleural effusions while mostly sparing the upper respiratory system [10]. It is believed that the lung damage results from an unchecked host immune response that produces an excess of pro-inflammatory cytokines [10][12]. Some individuals will experience superinfections with bacteria (e.g., Both Strenotrophomonas maltophilia and Staphylococcus aureus), viruses, or. fungi (e. g., The Aspergillus and Candida) [10]. The postmortem histopathology characteristics, which may not be typical of all SARS cases, include lung macrophage infiltration, diffuse alveolar destruction, and proliferation of epithelial cells [10].
The effects of severe acute respiratory syndrome on world health
The CDC, in partnership includes local and state health agencies, The World Health Organization (WHO), & adding other partners, keeps on examine instances of the severe acute respiratory syndrome (SARS). A total of 6,903 SARS cases from 29 countries, including the US, were reported to WHO between November 1, 2002, and May 7, 2003; 495 deaths (case-fatality proportion: 7.2%) were also reported. Information on SARS cases reported in the United States is updated in this report [13]. A sum total of 328 Cases of SARS were recorded from 38 states in the US as of May 7. Of these, 63 (19%) and 265 (81%) were categorized as probable and suspect SARS, respectively. (higher severity diseases marked by acute respiratory distress syndrome being present or pneumonia) (Figure 1: Table) Three (5%) out of the sixty-three likely Patients with SARS needed mechanical ventilation, and 42 (67%) were admitted to the hospital. In the US, there have been no reported SARS-related fatalities [14].
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For 69 cases, laboratory testing to assess Coronavirus linked to SARS (SARS-CoV) infection had been performed. According towards the previously published description, there have been six cases of SARS-CoV infection confirmed in a laboratory, all of which were likely situations (3,4). Ever since the last report, no newly confirmed reports of SARS-CoV had been found. For 63 instances (49 suspect and 14 probable), negative results (i.e., no antibodies in convalescent serum against SARS-CoV taken more than 21 days following the symptom start) had been reported [15][16]. One (2%) of the 63 potential SARS patients was someone who lived with a SARS patient., and another (2% was a medical facility. professional whom treated to the SARS patient. In the 10 days before to the commencement of sickness, the remaining 61 (97%) likely SARS patients had visited regions where SARS transmission had been reported or suspected (2). Thirteen (12%) had visited Toronto, Canada; five (8%) had visited Singapore: three (5%) had visited Vietnam's Hanoi; and 36 (59%) had visited mainland Hong Kong Special Administrative Region, China Region, China (Figure 2). In the ten days prior to the onset of sickness, eight (13%) likely patients had travelled to two or more SARS-infected locations. Two had visited Hong Kong, one had visited Hong Kong and Thailand, one had visited Hong Kong and Guangdong, China, one had been to Toronto, and the other had been to Singapore., out of six likely SARS patients who have positive Lab results for SARS-CoV [17].
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There has been no change in the SARS epidemiology in the US. significantly since last update most cases are still linked to journey, and there is little supplementary transmission among relationships (such as family members and medical personnel). To accurately explain the SARS epidemiology in the US & around world, convalescent serum collection and testing is still a top priority [18].
Targeted Drug Delivery Systems
They can be treated with a variety of medications, including oxygen therapy, immunomodulators, and bronchodilators. Nonetheless, there are still certain issues with medication side effects and efficacy. Targeted therapeutics and precise drug delivery systems are essential to the therapy of various disorders in order to maximise therapeutic success while minimising systemic side effects. The function of drug delivery systems in severe acute respiratory syndrome is the main topic of this thorough study. In particular, nanoparticle-based drug delivery systems, inhaled corticosteroids (ICSs), novel biologicals, gene therapy, and customized healthcare. We hope to offer a comprehensive understanding of the current situation & potential upcoming developments for the enhancing treatment leads to these challenging conditions through looking at latest developments & approaches in certain domains. Nowadays, a lot of focus is being placed on creating novel drug delivery methods based on nanoparticles which can target certain cells, including macrophages and cells of the lung epithelium, although reducing systemic adverse effects [19]. These methods encapsulate and distribute medications directly to the lungs' afflicted regions by using nano-particles, they are minuscule particles with sizes vary from 1 to 100 nanometres [20]. Researchers can improve the efficacy of medication delivery and lessen off-target effects by altering the surface characteristics of nanoparticles, which will increase their capacity to attach to particular lung cell types [21]. Additionally, delivery of drugs methods based on nano-particles can enhance the stability & prevent degradation of pharmaceuticals, guaranteeing long-lasting therapeutic benefits and sustained release [22].
1)Nanoparticle-Based Drug Delivery Systems
Nanotechnology applications continue to offer efficient methods for managing a range of long-term diseases and enhancing therapeutic results. A promising non-invasive therapy approach for achieving In the lungs, medication deposition and regulated release is use of nanocarrier frameworks, such as Micelles, nano-particles, and liposomes, for pulmonary drug delivery [19]. (Figure 1). In these systems, medications are delivered straight to the lungs' target cells using nanometre-sized manufactured particles [23]. Compared to traditional drug delivery techniques, nanoparticles offer a number of benefits, such as increased targeting, less toxicity, and greater bioavailability [24, 25].
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Figure 1: Nano-Carrier Devices Allow for Regulated Release and Drug Deposition in The Lungs.
Drugs that are hydrophilic or hydrophobic can be encapsulated in liposomes, which are spherical vesicles made of lipid bilayers [26]. Lipid nanoparticles (LNPs) can be engineered to improve biocompatibility, increase medication stability, and extend circulation time by varying their size, surface charge, and lipid composition [27]. Additionally, an LNP can be made capable of targeting by conjugating its surface with monoclonal antibodies [28], peptides [29], or small-molecule ligands [26]. For instance, macrophages frequently exhibit overexpression of folate receptors, which produces LNP combined with folate an excellent choice for the administering inflammatory-reducing medications [30]. Temperature, pH variations, enzymes, light, and other variables can all have an impact on the payload that LNPs carry. The best researched of these is the pH change mechanism, which can lead to a phase transition and increased membrane permeability in LNPs [31]. Apart from LNPs, there are a few more nanoparticles with unique properties (Table 1). Another type of nanoparticle is a micelle, which is made up of amphiphilic molecules arranged in a core-shell configuration [32]. They can readily pass across the elevated alveolar fluid barrier seen in chronic inflammatory lung disorders because of their high solubility. Budesonide's half-life in the lung can be effectively extended to 18–20 hours by a novel type of stabilised phospholipid nano micelles (SSMs) that can penetrate deep lung tissue [33]. Magnetic targeting, gene therapy, and medication (e.g., cancer treatments), as well as contrast-enhancing diagnostic imaging are just a few of many uses for magnetic nanoparticles (MNPs) created by the magnetofection approach in biological research and medicine [34, 35]. The Nanoparticles of superpara-magnetic iron oxide (SPION), a particular kind of nano-particle with the unique the magnetic that can be directed to certain bodily areas via an external magnetic field, serves as a prime example [36]. They are capable of precisely delivering medications coated on their surface, primarily certain molecular antibodies linked to inflammation, such as IL4Rα & ST2, to location of lesion of inflammation [37, 38]. To discharge its load in a regulated way, a type of nano-particles with selective organ targeting (SORT) was created. It can go after the inflammatory location within the lungs & other locations although exposing the least amount of robust tissue in other areas of body [39]. medication toxicity may be decreased and patient outcomes may be enhanced with this focused medication delivery strategy [40]. Hybrid nanoparticles (HNPs), which can concurrently have the properties of several nanoparticles, have become more and more common recently [41]. This has caused a trend of the investigating various nanoparticle combinations. {37,38,42,42,43,45,46,47}
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Researchers are looking into a number of potential future paths for drug delivery systems based on nanoparticles. For instance, scientists are creating novel mucus-penetrating nanoparticles (MPPs) because severe acute respiratory syndrome cause a lot of mucus to leak out of the lungs. According to research on uptake mechanisms, MPP absorption was facilitated via macropinocytosis and endocytosis mediated by caveolae [48]. Drug bioavailability increased by more than five times, according to in vivo research findings [49]. Others are looking into fresh approaches to surface modification and nanoparticle design optimisation to enhance drug release and targeting [42,50]. Furthermore, several researchers are looking into the possibility of combining nanoparticles with immunotherapy or gene therapy, among other treatment methods [51,52]. Lastly, there is significant interest in creating medication delivery strategies based on personalised nanoparticles that can be customised for each patient according to their own genetic profiles and illness characteristics [53]. Nanoparticles have capacity to decrease systemic adverse effects as well as increase therapeutic efficacy through targeted medication delivery. All things considered; medication delivery methods centered on nano-particles have numerous potential for treating long-term inflammatory respiratory conditions.
2)Inhaled Corticosteroids (ICSs)
Asthma and severe acute respiratory syndrome (SARS) are two common chronic respiratory conditions that are treated with inhaled corticosteroids (ICSs). By lowering the mediators of inflammation produced within the airways, these drugs help avoid / lessen bronchoconstriction, inflammation and the creation of mucous. As per study by Global Asthma Initiative (GINA) [54]. However, the effectiveness of ICS is currently limited by a few delivery-related issues. Finding the best way to distribute the drug throughout the lungs is a significant obstacle. The efficiency of ICS particles in the lower airways may be diminished if they become lodged in the mouth or throat [55]. Additionally, patients may struggle to use their inhaler appropriately, which could result in less effective and efficient medicine delivery [56]. Furthermore, because each patient's demands can differ greatly, it can be difficult to determine the right ICS dosage for them [57].
Numerous techniques have been devised to maximise the distribution of ICS and enhance its effectiveness. One strategy is the application of spacer technology, which aid as an improve pharmaceutical accumulation throughout lungs and slow down rate of medication delivery [58]. The creation of additional effective Formulations of ICS, including ICSs with tiny particles, which have demonstrated greater effectiveness when contrasted to traditional Formulations of ICS, is an additional strategy [59]. When compared to conventional ICSs, ICSs with tiny particles exhibit higher accumulation in the tiny airways [60]. A meta analysis found that tiny-particle ICSs have a far greater chance of controlling Asthma [61]. It is also worthwhile to optimise the mix of ICSs and other medications (Figure 2). Furthermore, new developments in research have looked into intelligent inhalers that are capable of track medicine compliance & give patients comments [62]. Nebulisers, pressurised Soft mist inhalers (SMIs), dry powder inhalers (DPIs), and metered-dose inhalers (pMDIs) are the four types of inhalers that are most frequently utilized today (Table 2). Because they allow for real-time inhalation plan control, artificial intelligence (AI)-based intelligent inhalers have garnered a lot of attention lately. For instance, the bioavailability of medications has been successfully increased by intelligent dry powder inhalers (DPIs) built using artificial neural networks (ANNs) [63]. However, more data is still required to train more sophisticated models that would produce better drug delivery plans [64].
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Figure 2: Some published studies have demonstrated a reduction in the rate of ECOPD from ICSs in combination along with additional medication routines [71,72,73,74,75,76]. Long-acting muscarinic antagonist is referred to as LAMA, and long-acting beta2-adrenergic Agonist; ECOPD for Chronic obstructive pulmonary disease exacerbation; and Inhaled corticosteroid (ICS). {65,66,67,68,69,70}
Table 2: Lists The Many Types of ICS Inhalers.
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Even if there have been significant improvements, it is crucial to recognise that there are still restrictions on the usage of ICSs that need for rigorous analysis and correction. Long-term use of ICSs, for instance, may raise the incidence of cataracts and pneumonia, according to certain research [77,78]. Furthermore, more investigation is required to ascertain the ideal ICS dosage and treatment plan for each patient [79].
There are multiple areas of concentration for future ICS delivery research. Research is being done on customised ICS dosing plans according to how serious illness is features of each Patient [80]. New ICS formulations that make use of cutting-edge drug delivery methods, such as nanotechnology and microencapsulation, are presently being investigated [81].
Therefore, ICSs continue to be a useful therapy choice for long-term respiratory conditions, but their safety and effectiveness depend on appropriate administration optimisation.
3)Novel Biologicals
The treatment of numerous respiratory conditions, including idiopathic pulmonary fibrosis (IPF), asthma, & SARS, or severe acute respiratory disease, had been transformed by biologicals, a class of medications made from living cells or organisms. Biologicals provide a more targeted and efficient therapy option than conventional drugs by focussing on particular proteins and immune cells that contribute to lung and airway inflammation and damage [82]. For biologicals to be effective, they must be delivered to the lungs efficiently. Nebulisers, dry powder inhalers, and intravenous infusions are just a few of the novel techniques that have been created to enhance drug delivery [83]. Furthermore, new opportunities for targeted medication administration to certain lung regions have been made possible by recent developments in nanotechnology [84]. For instance, it has been demonstrated that a novel Nano-medicine-targeted M2 macrophages with exosome membrane modifications is successful in treating In vivo allergic asthma [42]. Development of these deliveries systems offers possibility of obtaining the targeted organ-level activity of biopharmaceuticals. The two biggest trends in the future will surely be the development of tailored biological therapies and better medication delivery techniques. For instance, research has looked into the creation of intelligent inhalers capable of track compliance & give patients comments , as well as using biomarkers to determine individuals whom would gain from particular Biology [85]. Furthermore, studies are being conducted to create novel biologicals that target cells and pathways implicated in respiratory disorders [86]. By providing more accurate and focused treatments, biologicals have so far revolutionised the treatment of respiratory illnesses. To maximise these treatments' effectiveness, safety, and affordability, more study needs to be done.
4)Gene Therapy
A potential approach for treating respiratory disorders is gene therapy, including severe acute respiratory syndrome, pulmonary hypertension, alpha-1 antitrypsin deficiency, asthma, and cystic fibrosis. In This healing technique, genetic material is delivered to cells in order to introduce new genes, inhibit the expression of damaging genes, or replace or supplement defective genes [87]. Compared to conventional pharmaceutical treatments, gene therapy has the potential to produce long-lasting results. Multiple gene therapy strategies have been established for respiratory ailments, encompassing viral-vector delivery methods and CRISPR-associated protein 9 (CRISPR–Cas9) technologies. Viral vectors, including adeno-associated viruses (AAVs) and lentiviruses, are frequently employed to transport the therapeutic gene to target Cells. Adeno-associated viruses The AAVs have demonstrated potential within clinical studies for fibrosis of the cyst & many hereditary pulmonary disorders [88]. CRISPR–Cas9 technology facilitates accurate modification of faulty live cells' genes & has been employed to rectify Alpha-1 antitrypsin deficiency & cystic fibrosis mutations in animal models . Nonetheless, these methodologies are still constrained by limitations, including immunological reactions to the vectors of viruses & possible not on target consequences of modifying the genome . Gene therapy strategies for respiratory diseases require further optimization. This encompasses the advancement a more focused & effective delivery mechanisms, including nanoparticles in aerosol form for pulmonary- particular administration [89]. Inherent encapsulating ability regarding exosomes safeguards genetic material derived from destruction as well as the immune system assault, rendering them an exceptional delivery vehicle [90]. Furthermore, investigations are examining the integration of gene therapy with other modalities, including stem cell treatment, to augment therapeutic effectiveness [91]. Moreover, ethical questions about genome editing, such as possible unforeseen consequences as well as necessity for knowledgeable permission, necessitate ongoing discourse and inquiry. Gene therapy presents the possibility of enduring benefits in contrast to conventional pharmaceutical interventions. Continued The study is essential as an enhance Gene therapy's effectiveness and safety methods also to tackle The restrictions and moral issues related to This is potential treatment modality.
5)Personalized Medicine
Personalised medicine is a healthcare approach that accounts for individual differences in genetics, lifestyle & surroundings in the disease prevention, diagnosis, & treatment. Regarding respiratory conditions, personalised medication seeks as an customise methods of therapy according to patients' genetic and molecular profiles, along with other clinical and environmental considerations [92]. The implementation of This strategy may lower medical expenses while also improving patient outcomes. Through identifying biomarkers & additional parameters (such as immunoglobulins in serum & sputum microbiota, & prognostic biomarkers in imaging) that influence illness advancement & aggravation, Doctors are able to formulate Further tailored therapy strategies which reduce adverse effects & enhance effectiveness [93]. Recent studies in personalised medicine for respiratory diseases emphasise & discovery of biomarkers and the creation of diagnostic tools to enhance patient classification according to their fundamental mechanisms of illness. Gene expression profiles have been found through studies. linked to various COPD and asthma subtypes [94,95]. Scientists are investigating wearable sensors and other technologies for real-time monitoring of patient symptoms and disease activity, facilitating prompt actions & modifications to therapy regimens. Recent advancements in personalised medicine for respiratory diseases have demonstrated positive results, indicating enhanced patient well-being and potential cost savings in the healthcare system. A study on biomarker-guided asthma management demonstrated significant reductions in asthma exacerbations and healthcare utilisation relative to standard care [96]. Nonetheless, limitations persist in the application of personalised Clinical application of medicine, including the price and accessibility of diagnostic procedures and treatments, along with moral issues regarding the application of genetic data to treatment choices [97].
Enhancing precision & availability of diagnostic examinations, along with broadening spectrum of focused treatments for Patients, constitutes fundamental aspects Of personalised medication in respiratory conditions. Scientists are investigating application of techniques for machine learning and artificial intelligence to enhance the prediction of results for patients & determine best practices for treatment [98]. Furthermore, research is examining the potential advantages of integrating various specific treatments for individuals with intricate mechanisms of disease. Continued conversations regarding Concerns about ethics and regulations will influence creation & application of personalised clinical application of medicine. To sum up, personalised medication enables plans for treatment to be more focused, efficient, & customised to specific requires of individual patients. Further investigation is essential To tackle restrictions & moral implications of This method, as well as To enhance precision and availability of diagnostic procedures and treatments. Given It's significant Variability, personalised medical care must integratively merged to diverse treatment to enhance lung function in individuals suffering from acute respiratory distress syndrome.
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Figure 3: Patients Who Receive Various Therapy Benefit from Severe Acute Respiratory Syndrome.
Summary and outlooks for the future
Targeted drug delivery systems demonstrate potential in the treatment of SARS by administering medications directly to the impacted regions of the lungs. This method may enhance therapeutic efficacy, minimise systemic side effects, and improve patient outcomes. Targeted drug delivery systems, such as nanoparticle-based systems and inhalable formulations, are under investigation for their efficacy in treating SARS. Targeted drug delivery systems, which transport medication straight to the affected areas of the body—in this case, the lungs—are an intelligent approach to treating illnesses like SARS. Rather than dispersing the medication throughout the body, which may result in adverse consequences, these systems employ specialised carriers, such as liposomes or nanoparticles, to deliver medication precisely where it is required. This reduces adverse effects, increases therapeutic efficacy, and even reduces the dosage of medication required. Advanced techniques like inhalable medications, antibody-based carriers, and intelligent systems that only release medication when necessary are also being developed by scientists.
Targeted medication delivery has been seen as a potent weapon for combating SARS and other viruses of a similar nature in the future, despite obstacles such as high costs and safety tests. Creating new targeted delivery systems: Scientists are working to create more potent targeted delivery methods capable of focusing on lung cells precisely although reducing systemic adverse effects. Enhancing treatment results: The objective is to lessen adverse effects and enhance treatment results for SARS patients. By customising treatment to fulfil the requirements of each patient, targeted drug delivery can contribute to the advancement of personalised medicine.
Potential uses: Targeted delivery of drugs methods might also be used to treat influenza and COVID-19, among other respiratory illnesses. Researchers can enhance SARS and other respiratory disease treatment choices and eventually improve patient outcomes and save lives by developing customised drug delivery systems.
REFERENCES
Nilofar Raju Mujawar*, Manali Bhau Naik, Multimodal Targeted Drug Delivery Strategies for Severe Acute Respiratory Syndrome (SARS): Advances in Nanocarriers, Inhaled Corticosteroids (ICSs), Novel Biologicals, Gene Therapy, Personalized Medicines, Approaches, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 5, 2151-2170 https://doi.org/10.5281/zenodo.15397975
10.5281/zenodo.15397975
