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Pediatric Pulmonology Jan 2020
Topics: Humans; Infant, Newborn; Infant, Premature, Diseases; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn; Surface-Active Agents
PubMed: 31730302
DOI: 10.1002/ppul.24573 -
Pulmonary Pharmacology & Therapeutics Apr 2023The acute respiratory distress syndrome (ARDS) is a life-threatening condition that causes respiratory failure. Despite numerous clinical trials, there are no... (Review)
Review
The acute respiratory distress syndrome (ARDS) is a life-threatening condition that causes respiratory failure. Despite numerous clinical trials, there are no molecularly targeted pharmacologic therapies to prevent or treat ARDS. Drug delivery during ARDS is challenging due to the heterogenous nature of lung injury and occlusion of lung units by edema fluid and inflammation. Pulmonary drug delivery during ARDS offers several potential advantages including limiting the off-target and off-organ effects and directly targeting the damaged and inflamed lung regions. In this review we summarize recent ARDS clinical trials using both systemic and pulmonary drug delivery. We then discuss the advantages of pulmonary drug delivery and potential challenges to its implementation. Finally, we discuss the use of nanoparticle drug delivery and surfactant-based drug carriers as potential strategies for delivering therapeutics to the injured lung in ARDS.
Topics: Humans; Lung; Respiratory Distress Syndrome; Drug Delivery Systems; Pulmonary Surfactants; Drug Carriers
PubMed: 36682407
DOI: 10.1016/j.pupt.2023.102196 -
International Journal of Molecular... Jul 2023The alveolar epithelium is covered by a non-cellular layer consisting of an aqueous hypophase topped by pulmonary surfactant, a lipo-protein mixture with surface-active... (Review)
Review
The alveolar epithelium is covered by a non-cellular layer consisting of an aqueous hypophase topped by pulmonary surfactant, a lipo-protein mixture with surface-active properties. Exposure to cigarette smoke (CS) affects lung physiology and is linked to the development of several diseases. The macroscopic effects of CS are determined by several types of cell and molecular dysfunction, which, among other consequences, lead to surfactant alterations. The purpose of this review is to summarize the published studies aimed at uncovering the effects of CS on both the lipid and protein constituents of surfactant, discussing the molecular mechanisms involved in surfactant homeostasis that are altered by CS. Although surfactant homeostasis has been the topic of several studies and some molecular pathways can be deduced from an analysis of the literature, it remains evident that many aspects of the mechanisms of action of CS on surfactant homeostasis deserve further investigation.
Topics: Pulmonary Surfactants; Electronic Nicotine Delivery Systems; Surface-Active Agents; Nicotiana; Lung
PubMed: 37511463
DOI: 10.3390/ijms241411702 -
Journal of Perinatology : Official... Apr 2024Surfactant replacement therapy is currently approved by the United States Food and Drug Administration (FDA) for premature infants with respiratory distress syndrome... (Review)
Review
Surfactant replacement therapy is currently approved by the United States Food and Drug Administration (FDA) for premature infants with respiratory distress syndrome (RDS) caused by surfactant deficiency due to immaturity. There is strong evidence that surfactant decreases mortality and air leak syndromes in premature infants with RDS. However, surfactant is also used "off-label" for respiratory failure beyond classic RDS. This review discusses current evidence for the use of off-label surfactant therapy for (1) term infants with lung disease such as meconium aspiration syndrome (MAS), pneumonia/sepsis, and congenital diaphragmatic hernia (2) premature infants after 72 h for acute respiratory failure, and (3) the use of surfactant lavage. At last, we briefly describe the use of surfactants for drug delivery and the current evidence on evaluating infants for surfactant deficiency.
Topics: Infant, Newborn; Humans; Female; Surface-Active Agents; Meconium Aspiration Syndrome; Respiratory Distress Syndrome, Newborn; Pulmonary Surfactants; Infant, Premature
PubMed: 38459371
DOI: 10.1038/s41372-024-01921-7 -
Current Medicinal Chemistry 2022Pulmonary surfactant is a complex lipoprotein mixture secreted into the alveolar lumen by type 2 pneumocytes, which is composed by tens of different lipids... (Review)
Review
Pulmonary surfactant is a complex lipoprotein mixture secreted into the alveolar lumen by type 2 pneumocytes, which is composed by tens of different lipids (approximately 90% of its entire mass) and surfactant proteins (approximately 10% of the mass). It is crucially involved in maintaining lung homeostasis by reducing the values of alveolar liquid surface tension close to zero at end-expiration, thereby avoiding the alveolar collapse, and assembling a chemical and physical barrier against inhaled pathogens. A deficient amount of surfactant or its functional inactivation is directly linked to a wide range of lung pathologies, including the neonatal respiratory distress syndrome. This paper reviews the main biophysical concepts of surfactant activity and its inactivation mechanisms, and describes the past, present and future roles of surfactant replacement therapy, focusing on the exogenous surfactant preparations marketed worldwide and new formulations under development. The closing section describes the pulmonary surfactant in the context of drug delivery. Thanks to its peculiar composition, biocompatibility, and alveolar spreading capability, the surfactant may work not only as a shuttle to the branched anatomy of the lung for other drugs but also as a modulator for their release, leading to innovative therapeutic avenues for the treatment of several respiratory diseases.
Topics: Biocompatible Materials; Drug Delivery Systems; Humans; Infant, Newborn; Lung; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn
PubMed: 34525915
DOI: 10.2174/0929867328666210825110421 -
Biomedical Journal Dec 2021The knowledge about surfactant biology is now deeper and recent research has allowed to clarify its role in several human lung disorders. The balance between surfactant... (Review)
Review
The knowledge about surfactant biology is now deeper and recent research has allowed to clarify its role in several human lung disorders. The balance between surfactant production and consumption is better known and the same applies to their regulatory mechanisms. This has allowed to hypothesize and investigate several new and original strategies to protect surfactant and enhance its activity. These interventions are potentially useful for several disorders and particularly for acute respiratory distress syndrome. We here highlight the mechanisms regulating surfactant consumption, encompassing surfactant catabolism but also surfactant injury due to other mechanisms, in a physiopathology-driven fashion. We then analyze each corresponding strategy to protect surfactant and enhance its activity. Some of these strategies are more advanced in terms of research & development pathway, some others are still investigational, but all are promising and deserve a joint effort from clinical-academic researchers and the industry.
Topics: Humans; Lung; Pulmonary Surfactants; Respiratory Distress Syndrome; Surface-Active Agents
PubMed: 34365021
DOI: 10.1016/j.bj.2021.07.011 -
International Journal of Molecular... Apr 2020Gas exchange in the lung takes place via the air-blood barrier in the septal walls of alveoli. The tissue elements that oxygen molecules have to cross are the alveolar... (Review)
Review
Gas exchange in the lung takes place via the air-blood barrier in the septal walls of alveoli. The tissue elements that oxygen molecules have to cross are the alveolar epithelium, the interstitium and the capillary endothelium. The epithelium that lines the alveolar surface is covered by a thin and continuous liquid lining layer. Pulmonary surfactant acts at this air-liquid interface. By virtue of its biophysical and immunomodulatory functions, surfactant keeps alveoli open, dry and clean. What needs to be added to this picture is the glycocalyx of the alveolar epithelium. Here, we briefly review what is known about this glycocalyx and how it can be visualized using electron microscopy. The application of colloidal thorium dioxide as a staining agent reveals differences in the staining pattern between type I and type II alveolar epithelial cells and shows close associations of the glycocalyx with intraalveolar surfactant subtypes such as tubular myelin. These morphological findings indicate that specific spatial interactions between components of the surfactant system and those of the alveolar epithelial glycocalyx exist which may contribute to the maintenance of alveolar homeostasis, in particular to alveolar micromechanics, to the functional integrity of the air-blood barrier, to the regulation of the thickness and viscosity of the alveolar lining layer, and to the defence against inhaled pathogens. Exploring the alveolar epithelial glycocalyx in conjunction with the surfactant system opens novel physiological perspectives of potential clinical relevance for future research.
Topics: Alveolar Epithelial Cells; Animals; Glycocalyx; Humans; Pulmonary Alveoli; Pulmonary Surfactants; Respiratory Mucosa
PubMed: 32349261
DOI: 10.3390/ijms21093075 -
The Cochrane Database of Systematic... Feb 2020In the 1960s and 1970s, pulmonary haemorrhage (PH) occurred mainly in full-term infants with pre-existing illness with an incidence of 1.3 per 1000 live births. Risk... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In the 1960s and 1970s, pulmonary haemorrhage (PH) occurred mainly in full-term infants with pre-existing illness with an incidence of 1.3 per 1000 live births. Risk factors for PH included severity of illness, intrauterine growth restriction, patent ductus arteriosus (PDA), coagulopathy and the need for assisted ventilation. Presently, PH occurs in 3% to 5% of preterm ventilated infants with severe respiratory distress syndrome (RDS) who often have a PDA and have received surfactant. The cause of PH is thought to be due to rapid lowering of intrapulmonary pressure, which facilitates left to right shunting across a PDA and an increase in pulmonary blood flow. Retrospective case reports and one prospective uncontrolled study have shown promising results for surfactant in treating PH.
OBJECTIVES
To evaluate the effect of surfactant treatment compared to placebo or no intervention on mortality and morbidities in neonates with PH.
SEARCH METHODS
For this update The Cochrane Library, Issue 2, 2012; MEDLINE; EMBASE; CINAHL; Clinicaltrials.gov; Controlled-trials.com; proceedings (2000 to 2011) of the Annual Meetings of the Pediatric Academic Societies (Abstracts2View) and Web of Science were searched on 8 February 2012.
SELECTION CRITERIA
Randomised or quasi-randomised controlled trials that evaluated the effect of surfactant in the treatment of PH in intubated term or preterm (< 37 weeks) neonates with PH. Infants were included up to 44 weeks' postmenstrual age. The interventions studied were intratracheal instillation of surfactant (natural or synthetic, regardless of dose) versus placebo or no intervention.
DATA COLLECTION AND ANALYSIS
If studies were identified by the literature search, the planned analyses included risk ratio, risk difference, number needed to treat to benefit or to harm for dichotomous outcomes, and mean difference for continuous outcomes, with their 95% confidence intervals. A fixed-effect model would be used for meta-analyses. The risk of bias for included trials would be assessed. Heterogeneity tests, including the I statistic, would be performed to assess the appropriateness of pooling the data and the results would be reported.
MAIN RESULTS
No trials were identified.
AUTHORS' CONCLUSIONS
No randomised or quasi-randomised trials that evaluated the effect of surfactant in PH were identified. Therefore, no conclusions from such trials can be drawn. In view of the promising results from studies with less strict study designs than a randomised controlled trial, there is reason to conduct further trials of surfactant for the treatment of PH in neonates.
Topics: Hemorrhage; Humans; Infant, Newborn; Infant, Premature; Lung Diseases; Pulmonary Surfactants; Randomized Controlled Trials as Topic
PubMed: 32012227
DOI: 10.1002/14651858.CD005254.pub4 -
Biomaterials Advances Jul 2023Lung cancer is often diagnosed at an advanced stage where tumors are usually inoperable and first-line therapies are inefficient and have off-targeted adverse effects,...
Lung cancer is often diagnosed at an advanced stage where tumors are usually inoperable and first-line therapies are inefficient and have off-targeted adverse effects, resulting in poor patient survival. Here, we report the development of an inhalable poly lactic-co-glycolic acid polymer-based nanoparticle (PLGA-NP) formulation with a biomimetic Infasurf® lung surfactant (LS) coating, for localized and sustained lung cancer drug delivery. The nanoparticles (188 ± 7 nm) were stable in phosphate buffered saline, serum and Gamble's solution (simulated lung fluid), and demonstrated cytocompatibility up to 1000 μg/mL concentration and dose-dependent uptake by lung cancer cells. The LS coating significantly decreased nanoparticle (NP) uptake by NR8383 alveolar macrophages in vitro compared to uncoated NPs. The coating, however, did not impair NP uptake by A549 lung adenocarcinoma cells. The anti-cancer drug gemcitabine hydrochloride encapsulated in the PLGA core was released in a sustained manner while the paclitaxel loaded in the LS shell demonstrated a rapid or burst release profile over 21 days. The drug-loaded NPs significantly decreased cancer cell survival and colony formation in vitro compared to free drugs and single drug-loaded NPs. In vivo studies confirmed greater retention of LS-coated NPs in the lungs of C57BL/6 WT mice compared to uncoated NPs, at 24 h and 72 h following intranasal administration. The overall results confirm that LS coating is a unique strategy for cloaking polymeric NPs to potentially prevent their rapid lung clearance and facilitate prolonged pulmonary drug delivery.
Topics: Mice; Animals; Polymers; Polylactic Acid-Polyglycolic Acid Copolymer; Mice, Inbred C57BL; Lung; Lung Neoplasms; Pulmonary Surfactants; Nanoparticles; Surface-Active Agents
PubMed: 37104963
DOI: 10.1016/j.bioadv.2023.213430 -
Seminars in Fetal & Neonatal Medicine Dec 2023Surfactant replacement therapy (SRT) has revolutionized the management of respiratory distress syndrome (RDS) in premature infants, leading to improved survival rates... (Review)
Review
Surfactant replacement therapy (SRT) has revolutionized the management of respiratory distress syndrome (RDS) in premature infants, leading to improved survival rates and decreased morbidity. SRT may, however, be associated with hemodynamic changes, which can have both positive and negative effects on the immature cardiovascular system, during the transitional adaptation from fetal to extrauterine environment. However, there is a relative paucity of evidence in this domain, with most of them derived from small heterogeneous observational studies providing conflicting results. In this review, we will discuss the hemodynamic changes that occur with surfactant administration during this vulnerable period, focusing on available evidence regarding changes in pulmonary and systemic blood flow, cerebral circulation and their clinical implications.
Topics: Humans; Infant, Newborn; Hemodynamics; Infant, Premature; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn; Surface-Active Agents; Observational Studies as Topic
PubMed: 38040585
DOI: 10.1016/j.siny.2023.101498