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1.
Life Sci ; 285: 119969, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34547339

RESUMO

Inflammatory lung diseases related morbidity and mortality impose a significant financial burden. Inflammation is a hallmark of many diseases of the respiratory system which is directly or indirectly linked to adverse health conditions, air pollution, rapid lifestyle changes, and regular outbreaks of microbial infections. The unique anatomical and physiological features of the lungs make them an ideal target organ in the treatment of inflammatory respiratory disease and with the help of inhaled therapy lungs can be targeted directly. The principal objective of this review is to present the comprehensive role of inhaled nano-based therapeutics such as liposomes, niosomes, nanoparticles, nanoemulsion, nanosuspension, and exosomes in the treatment and management of inflammatory respiratory diseases. Inhaled nanomedicines provide targeted diagnosis and treatment, improved drug solubility and distribution, prevent first-pass hepatic metabolism, improved patient compliance, and reduced drug side effects. They overcome several biological barriers in the human body and provide immediate, and quick-onset of action. Future research should be focused on improving the therapeutic efficiency of inhaled nanocarriers and to carry out in-depth mechanistic studies to translate current scientific knowledge for the efficient management of inflammatory lung diseases with minimal or no toxicity.

2.
Int J Mol Sci ; 22(16)2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34445609

RESUMO

Respiratory disease is the leading cause of death in children under the age of 5 years old. Currently available treatments for paediatric respiratory diseases including bronchopulmonary dysplasia, asthma, cystic fibrosis and interstitial lung disease may ameliorate symptoms but do not offer a cure. Cellular therapy may offer a potential cure for these diseases, preventing disease progression into adulthood. Induced pluripotent stem cells, mesenchymal stromal cells and their secretome have shown great potential in preclinical models of lung disease, targeting the major pathological features of the disease. Current research and clinical trials are focused on the adult population. For cellular therapies to progress from preclinical studies to use in the clinic, optimal cell type dosage and delivery methods need to be established and confirmed. Direct delivery of these therapies to the lung as aerosols would allow for lower doses with a higher target efficiency whilst avoiding potential effect of systemic delivery. There is a clear need for research to progress into the clinic for the treatment of paediatric respiratory disease. Whilst research in the adult population forms a basis for the paediatric population, varying disease pathology and anatomical differences in paediatric patients means a paediatric-centric approach must be taken.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos/métodos , Doenças Respiratórias/terapia , Criança , Humanos , Doenças Respiratórias/patologia
3.
Drug Deliv ; 28(1): 1496-1500, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34259091

RESUMO

COVID-19 can cause serious respiratory complications resulting in the need for invasive ventilatory support and concurrent aerosol therapy. Aerosol therapy is considered a high risk procedure for the transmission of patient derived infectious aerosol droplets. Critical-care workers are considered to be at a high risk of inhaling such infectious droplets. The objective of this work was to use noninvasive optical methods to visualize the potential release of aerosol droplets during aerosol therapy in a model of an invasively ventilated adult patient. The noninvasive Schlieren imaging technique was used to visualize the movement of air and aerosol. Three different aerosol delivery devices: (i) a pressurized metered dose inhaler (pMDI), (ii) a compressed air driven jet nebulizer (JN), and (iii) a vibrating mesh nebulizer (VMN), were used to deliver an aerosolized therapeutic at two different positions: (i) on the inspiratory limb at the wye and (ii) on the patient side of the wye, between the wye and endotracheal tube, to a simulated intubated adult patient. Irrespective of position, there was a significant release of air and aerosol from the ventilator circuit during aerosol delivery with the pMDI and the compressed air driven JN. There was no such release when aerosol therapy was delivered with a closed-circuit VMN. Selection of aerosol delivery device is a major determining factor in the release of infectious patient derived bioaerosol from an invasively mechanically ventilated patient receiving aerosol therapy.


Assuntos
Aerossóis , COVID-19 , Transmissão de Doença Infecciosa/prevenção & controle , Inaladores Dosimetrados , Nebulizadores e Vaporizadores , Respiração Artificial/métodos , Terapia Respiratória , Aerossóis/administração & dosagem , Aerossóis/efeitos adversos , COVID-19/fisiopatologia , COVID-19/terapia , COVID-19/transmissão , Terapia Combinada , Sistemas de Liberação de Medicamentos/instrumentação , Sistemas de Liberação de Medicamentos/métodos , Sistemas de Liberação de Medicamentos/normas , Humanos , Exposição Ocupacional/prevenção & controle , Projetos de Pesquisa , Terapia Respiratória/efeitos adversos , Terapia Respiratória/instrumentação , Terapia Respiratória/métodos , Gestão de Riscos , SARS-CoV-2
5.
Life Sci ; 280: 119744, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34174324

RESUMO

Viral respiratory tract infections have significantly impacted global health as well as socio-economic growth. Respiratory viruses such as the influenza virus, respiratory syncytial virus (RSV), and the recent SARS-CoV-2 infection (COVID-19) typically infect the upper respiratory tract by entry through the respiratory mucosa before reaching the lower respiratory tract, resulting in respiratory disease. Generally, vaccination is the primary method in preventing virus pathogenicity and it has been shown to remarkably reduce the burden of various infectious diseases. Nevertheless, the efficacy of conventional vaccines may be hindered by certain limitations, prompting the need to develop novel vaccine delivery vehicles to immunize against various strains of respiratory viruses and to mitigate the risk of a pandemic. In this review, we provide an insight into how polymer-based nanoparticles can be integrated with the development of vaccines to effectively enhance immune responses for combating viral respiratory tract infections.


Assuntos
Nanopartículas/química , Polímeros/química , Infecções Respiratórias/prevenção & controle , Infecções Respiratórias/virologia , Vacinação , Vacinas Virais/administração & dosagem , Animais , COVID-19/prevenção & controle , COVID-19/virologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/virologia , Portadores de Fármacos/química , Humanos , Influenza Humana/prevenção & controle , Influenza Humana/virologia , Infecções por Orthomyxoviridae/prevenção & controle , Infecções por Orthomyxoviridae/virologia , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Infecções por Vírus Respiratório Sincicial/virologia , Vacinação/métodos , Vacinas Virais/uso terapêutico
8.
Crit Rev Food Sci Nutr ; : 1-15, 2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-33977840

RESUMO

Respiratory diseases, both acute and chronic, are reported to be the leading cause of morbidity and mortality, affecting millions of people globally, leading to high socio-economic burden for the society in the recent decades. Chronic inflammation and decline in lung function are the common symptoms of respiratory diseases. The current treatment strategies revolve around using appropriate anti-inflammatory agents and bronchodilators. A range of anti-inflammatory agents and bronchodilators are currently available in the market; however, the usage of such medications is limited due to the potential for various adverse effects. To cope with this issue, researchers have been exploring various novel, alternative therapeutic strategies that are safe and effective to treat respiratory diseases. Several studies have been reported on the possible links between food and food-derived products in combating various chronic inflammatory diseases. Nutraceuticals are examples of such food-derived products which are gaining much interest in terms of its usage for the well-being and better human health. As a consequence, intensive research is currently aimed at identifying novel nutraceuticals, and there is an emerging notion that nutraceuticals can have a positive impact in various respiratory diseases. In this review, we discuss the efficacy of nutraceuticals in altering the various cellular and molecular mechanisms involved in mitigating the symptoms of respiratory diseases.

11.
Int J Pharm ; 599: 120407, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33675930

RESUMO

Polymeric nanoparticles (NPs) are recognized as potential delivery vehicles for vaccines. PLGA is a biocompatible polymer synonymous with polymeric NPs, which can be coated with other polymers such as chitosan that has intrinsic adjuvant properties as well as mucoadhesive properties. Numerous modifications and variations exist for PLGA and chitosan, which can influence the NP characteristics and the resulting immunogenicity. The current study investigated variations for making chitosan coated PLGA NPs incorporating recombinant pneumococcal surface protein A from family 2, clade 4 (PspA4Pro) antigen as a vaccine targeting the vast majority of pneumococcal strains and determine the effect of the polymers on particle size, surface charge, and surface marker upregulation on a dendritic cell (DC) line in vitro. PLGA variations tested with the ester-terminal group had the greatest detriment for prospective vaccine use, due to the lowest PspA4Pro adsorption and induction of CD40 and CD86 cell surface markers on DCs. The negatively charged chitosans exhibited the lowest surface marker expressions, similar to the uncoated NP, supporting the commonly accepted notion that positive surface charge augments immunogenic effects of the NPs. However, the study indicated that NPs made from PLGA with an acid terminated group, and chitosan HCl salt, exhibit particle characteristics, antigen adsorption efficiency and immunogenicity, which could be most suitable as a vaccine formulation.


Assuntos
Quitosana , Nanopartículas , Antígenos de Superfície , Proteínas de Membrana , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Polímeros , Estudos Prospectivos
12.
BMJ Open Respir Res ; 8(1)2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33771812

RESUMO

BACKGROUND: The COVID-19 pandemic has highlighted the need for alternative short-term, reliable means to aid in the treatment of patients requiring ventilatory support. Concurrent aerosol drug delivery is often prescribed to such patients. As such, this study examines one such short-term option, the disposable gas-powered transport ventilator to effectively deliver aerosol therapy. Factors such as aerosol generator type, patient breathing pattern, humidification and nebuliser position within the respiratory circuit were also examined. METHODS: Aerosol drug delivery characterisation was undertaken using two different disposable transport ventilators (DTVs). Two different nebuliser types, a closed circuit vibrating mesh nebuliser (VMN) and an open circuit jet nebuliser (JN), at different locations in a respiratory circuit, proximal and distal to an endotracheal tube (ETT), with and without passive humidification, were evaluated in simulated adult and paediatric patients. RESULTS: Placement of a nebuliser proximal to the ETT (VMN: 25.19%-34.15% and JN: 3.14%-8.92%), and the addition of a heat and moisture exchange filter (VMN: 32.37%-40.43% and JN: 5.60%-9.91%) resulted in the largest potential lung dose in the adult patient model. Irrespective of nebuliser position and humidification in the respiratory circuit, use of the VMN resulted in the largest potential lung dose (%). A similar trend was recorded in the paediatric model data, where the largest potential lung dose was recorded with both nebuliser types placed proximal to the ETT (VMN: 8.12%-10.89% and JN: 2.15%-3.82%). However, the addition of a heat and moisture exchange filter had no statistically significant effect on the potential lung dose (%) a paediatric patient would receive (p>>0.05). CONCLUSIONS: This study demonstrates that transport ventilators, such as DTVs, can be used concurrently with aerosol generators to effectively deliver aerosolised medication in both adult and paediatric patients.


Assuntos
COVID-19/terapia , Equipamentos Descartáveis , Nebulizadores e Vaporizadores , Respiração Artificial/instrumentação , Respiração Artificial/métodos , Administração por Inalação , Aerossóis , Albuterol/uso terapêutico , Sistemas de Liberação de Medicamentos , Desenho de Equipamento , Humanos , Técnicas In Vitro , SARS-CoV-2
13.
Life Sci ; 276: 119436, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33789146

RESUMO

Non-small cell lung cancer (NSCLC) is one of the major causes of cancer-related mortality globally. Despite the availability of therapeutic options, the improvement in patient survival is yet to be achieved. Recent advances in natural product (e.g., Rutin) research, therapeutic nanotechnology and especially the combination of both could aid in achieving significant improvements in the treatment or management of NSCLC. In this study, we explore the anti-cancer activity of Rutin-loaded liquid crystalline nanoparticles (LCNs) in an in vitro model where we have employed the A549 human lung epithelial carcinoma cell line. The anti-proliferative activity was determined by MTT and Trypan blue assays, whereas, the anti-migratory activity was evaluated by the scratch wound healing assay and a modified Boyden chamber assay. We also evaluated the anti-apoptotic activity by Annexin V-FITC staining, and the colony formation activity was studied using crystal violet staining. Here, we report that Rutin-LCNs showed promising anti-proliferative and anti-migratory activities. Furthermore, Rutin-LCNs also induced apoptosis in the A549 cells and inhibited colony formation. The findings warrant further detailed and in-depth anti-cancer mechanistic studies of Rutin-LCNs with a focus towards a potential therapeutic option for NSCLC. LCNs may help to enhance the solubility of Rutin used in the treatment of lung cancer and hence enhance the anticancer effect of Rutin.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Movimento Celular , Proliferação de Células , Cristais Líquidos/química , Neoplasias Pulmonares/tratamento farmacológico , Nanopartículas/administração & dosagem , Rutina/farmacologia , Células A549 , Apoptose , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/patologia , Nanopartículas/química , Rutina/administração & dosagem , Rutina/química
15.
Life Sci ; 267: 118973, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33400932

RESUMO

Eosinophils are bi-lobed, multi-functional innate immune cells with diverse cell surface receptors that regulate local immune and inflammatory responses. Several inflammatory and infectious diseases are triggered with their build up in the blood and tissues. The mobilization of eosinophils into the lungs is regulated by a cascade of processes guided by Th2 cytokine generating T-cells. Recruitment of eosinophils essentially leads to a characteristic immune response followed by airway hyperresponsiveness and remodeling, which are hallmarks of chronic respiratory diseases. By analysing the dynamic interactions of eosinophils with their extracellular environment, which also involve signaling molecules and tissues, various therapies have been invented and developed to target respiratory diseases. Having entered clinical testing, several eosinophil targeting therapeutic agents have shown much promise and have further bridged the gap between theory and practice. Moreover, researchers now have a clearer understanding of the roles and mechanisms of eosinophils. These factors have successfully assisted molecular biologists to block specific pathways in the growth, migration and activation of eosinophils. The primary purpose of this review is to provide an overview of the eosinophil biology with a special emphasis on potential pharmacotherapeutic targets. The review also summarizes promising eosinophil-targeting agents, along with their mechanisms and rationale for use, including those in developmental pipeline, in clinical trials, or approved for other respiratory disorders.


Assuntos
Eosinófilos/imunologia , Transtornos Respiratórios/imunologia , Doenças Respiratórias/imunologia , Animais , Citocinas/imunologia , Citocinas/metabolismo , Eosinófilos/efeitos dos fármacos , Eosinófilos/metabolismo , Humanos , Pulmão/metabolismo , Pulmão/patologia , Transtornos Respiratórios/metabolismo , Transtornos Respiratórios/fisiopatologia , Doenças Respiratórias/metabolismo , Doenças Respiratórias/fisiopatologia , Células Th2/imunologia , Células Th2/metabolismo
16.
J Immunol ; 206(3): 652-663, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33328212

RESUMO

A vaccine providing both powerful Ab and cross-reactive T cell immune responses against influenza viruses would be beneficial for both humans and pigs. In this study, we evaluated i.m., aerosol (Aer), and simultaneous systemic and respiratory immunization (SIM) by both routes in Babraham pigs, using the single cycle candidate influenza vaccine S-FLU. After prime and boost immunization, pigs were challenged with H1N1pdm09 virus. i.m.-immunized pigs generated a high titer of neutralizing Abs but poor T cell responses, whereas Aer induced powerful respiratory tract T cell responses but a low titer of Abs. SIM pigs combined high Ab titers and strong local T cell responses. SIM showed the most complete suppression of virus shedding and the greatest improvement in pathology. We conclude that SIM regimes for immunization against respiratory pathogens warrant further study.


Assuntos
Vírus da Influenza A Subtipo H1N1/fisiologia , Vacinas contra Influenza/imunologia , Influenza Humana/imunologia , Infecções por Orthomyxoviridae/imunologia , Linfócitos T/imunologia , Aerossóis , Animais , Formação de Anticorpos , Modelos Animais de Doenças , Resistência à Doença , Humanos , Imunidade Celular , Imunização , Injeções Intramusculares , Suínos
17.
Int J Pharm, v. 599, 120407, abr. 2021
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: bud-3628

RESUMO

Polymeric nanoparticles (NPs) are recognized as potential delivery vehicles for vaccines. PLGA is a biocompatible polymer synonymous with polymeric NPs, which can be coated with other polymers such as chitosan that has intrinsic adjuvant properties as well as mucoadhesive properties. Numerous modifications and variations exist for PLGA and chitosan, which can influence the NP characteristics and the resulting immunogenicity. The current study investigated variations for making chitosan coated PLGA NPs incorporating recombinant pneumococcal surface protein A from family 2, clade 4 (PspA4Pro) antigen as a vaccine targeting the vast majority of pneumococcal strains and determine the effect of the polymers on particle size, surface charge, and surface marker upregulation on a dendritic cell (DC) line in vitro. PLGA variations tested with the ester-terminal group had the greatest detriment for prospective vaccine use, due to the lowest PspA4Pro adsorption and induction of CD40 and CD86 cell surface markers on DCs. The negatively charged chitosans exhibited the lowest surface marker expressions, similar to the uncoated NP, supporting the commonly accepted notion that positive surface charge augments immunogenic effects of the NPs. However, the study indicated that NPs made from PLGA with an acid terminated group, and chitosan HCl salt, exhibit particle characteristics, antigen adsorption efficiency and immunogenicity, which could be most suitable as a vaccine formulation.

18.
Nanomedicine (Lond) ; 15(30): 2933-2953, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33241979

RESUMO

Aim: Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine, which has been shown to promote disease severity in cystic fibrosis. Methods: In this study, aerosolized drug-loaded nanoparticles containing SCD-19, an inhibitor of MIF's tautomerase enzymatic activity, were developed and characterized. Results: The aerosolized nanoparticles had an optimal droplet size distribution for deep lung deposition, with a high degree of biocompatibility and significant cellular uptake. Conclusion: For the first time, we have developed an aerosolized nano-formulation against MIF's enzymatic activity that achieved a significant reduction in the inflammatory response of macrophages, and inhibited Pseudomonas aeruginosa biofilm formation on airway epithelial cells. This represents a potential novel adjunctive therapy for the treatment of P. aeruginosa infection in cystic fibrosis.

19.
Front Immunol ; 11: 594470, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33193445

RESUMO

Recent evidence indicates that local immune responses and tissue resident memory T cells (TRM) are critical for protection against respiratory infections but there is little information on the contributions of upper and lower respiratory tract (URT and LRT) immunity. To provide a rational basis for designing methods for optimal delivery of vaccines to the respiratory tract in a large animal model, we investigated the distribution of droplets generated by a mucosal atomization device (MAD) and two vibrating mesh nebulizers (VMNs) and the immune responses induced by delivery of influenza virus by MAD in pigs. We showed that droplets containing the drug albuterol, a radiolabel (99mTc-DTPA), or a model influenza virus vaccine (S-FLU) have similar aerosol characteristics. 99mTc-DTPA scintigraphy showed that VMNs deliver droplets with uniform distribution throughout the lungs as well as the URT. Surprisingly MAD administration (1ml/nostril) also delivered a high proportion of the dose to the lungs, albeit concentrated in a small area. After MAD administration of influenza virus, antigen specific T cells were found at high frequency in nasal turbinates, trachea, broncho-alveolar lavage, lungs, tracheobronchial nodes, and blood. Anti-influenza antibodies were detected in serum, BAL and nasal swabs. We conclude that the pig is useful for investigating optimal targeting of vaccines to the respiratory tract.


Assuntos
Vírus da Influenza A/imunologia , Vacinas contra Influenza/imunologia , Infecções por Orthomyxoviridae/veterinária , Doenças dos Suínos/prevenção & controle , Doenças dos Suínos/virologia , Imunidade Adaptativa , Administração Intranasal , Aerossóis , Animais , Anticorpos Antivirais/imunologia , Modelos Animais de Doenças , Humanos , Imunofenotipagem , Vacinas contra Influenza/administração & dosagem , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Pulmão/virologia , Suínos , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo
20.
Pharmaceutics ; 12(10)2020 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-32993197

RESUMO

Advanced Therapeutic Medicinal Products (ATMP) are a heterogenous group of investigational medicinal products at the forefront of innovative therapies with direct applicability in respiratory diseases. ATMPs include, but are not limited to, stem cells, their secretome, or extracellular vesicles, and each have shown some potential when delivered topically within the lung. This review focuses on that subset of ATMPs. One key mode of delivery that has enabling potential in ATMP validation is aerosol-mediated delivery. The selection of the most appropriate aerosol generator technology is influenced by several key factors, including formulation, patient type, patient intervention, and healthcare economics. The aerosol-mediated delivery of ATMPs has shown promise for the treatment of both chronic and acute respiratory disease in pre-clinical and clinical trials; however, in order for these ATMP device combinations to translate from the bench through to commercialization, they must meet the requirements set out by the various global regulatory bodies. In this review, we detail the potential for ATMP utility in the lungs and propose the nebulization of ATMPs as a viable route of administration in certain circumstances. Further, we provide insight to the current regulatory guidance for nascent ATMP device combination product development within the EU and US.

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