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Surfactant aerosol therapy for nRDS and ARDS
Published in Anthony J. Hickey, Heidi M. Mansour, Inhalation Aerosols, 2019
The various surfactant preparations consist of either pure lipids, animal-derived surfactants, or synthetically manufactured surfactants, each of these having different physicochemical properties. Exosurf, a mixture of phospholipids that lacks the apoproteins SP-B and SP-C, is not as effective as preparations containing one or both of these proteins and has been withdrawn from clinical use. The properties of proteins in the surfactant are important for both its surface activity as well as its anti-inflammatory, anti-infective, and lung-protective functions (28). Surfactants with SP-A, SP-B, SP-C, and SP-D proteins exhibit superior properties compared to some early surfactants where these proteins were either absent or markedly reduced (29–33). These proteins also contribute to the resistance of surfactant to metabolic breakdown, which makes them more attractive for use in the treatment of ARDS (34); CLSE (Infasurf) is the most resilient to degradation (35). Of these, SP-B and SP-C are the most important proteins that aid in the lowering of dynamic surface tension and surfactant spreading. In synthesized surfactants, one or both of these has been replaced by mimetics, such as KL4 (36) or by peptide analogs, such as Minipeptide in Minisurf (Molecular Express) (29). Synsurf incorporates two polymers to mimic the hydrophilic and hydrophobic nature of SP-B in a phospholipid mixture (37). The mixture was shown to be partly effective in improving lung function in an adult rabbit lung washout model of lung injury. Inclusion of polymers dextran and hyaluronan has also been demonstrated to improve the effectiveness of a bovine calf-derived surfactant, Infasurf (38). The polymers change both the viscosity of the surfactant suspensions and the morphology of these suspensions in manners that are surfactant-, concentration-, and temperature-dependent (39). It has been proposed that the interaction of surfactant with hyaluronan leads to irreversible structural changes that result in a surfactant with better surface activity and the potential to overcome inactivation (40). The synthetic surfactant, CHF 5633, which includes SP-B and SP-C mimetics, when instilled in multiple doses of 200 mg/kg into a premature lamb model that had been previously treated with the known surfactant inhibitor, albumin, resulted in improved lung compliance, lung morphology, and survival compared to poractant alfa (31).
Clinical considerations when treating neonatal aspiration syndromes
Published in Expert Review of Respiratory Medicine, 2019
Andrea Calkovska, Daniela Mokra, Vladimir Calkovsky, Katarina Matasova, Mirko Zibolen
The first weeks of life are unique in the sense of the high risk of morbidity and mortality. It is important to understand that aspirated material may induce clinical and histological signs similar to those seen in pediatric and adult patients with ARDS. The key weakness of clinical management so far is that treatment is mostly symptomatic and supportive. When treating aspiration syndromes, one should keep in mind the problems with inflammation and secondary surfactant inactivation, which are key pathophysiological features of this condition and an important starting point for treatment. Much research was performed in the area of the therapeutic use of exogenous surfactant, yet there is still not enough evidence to support its routine use in clinical practice for this indication. Surfactant supplementation, however, should be considered in babies with respiratory failure, following aspiration with significant respiratory support. In these cases, the appropriate dose and time of administration must be specified [83,88]. Newly developed synthetic surfactants may be more resistant to inactivation, so they can be of benefit in aspiration syndromes, which is supported by animal studies. A synthetic surfactant CHF5633 containing SP-B and SP-C analogs was more resistant than poractant alfa in terms of lipid peroxidation in newborn pigs with meconium aspiration [110]. In newborn lambs with MAS lucinactant, based on the synthetic peptide sinapultide (KL4), it was proven to be an effective and safe alternative to treatment [111].
Future of nanomedicines for treating respiratory diseases
Published in Expert Opinion on Drug Delivery, 2019
Over the years, an increasing number of nanoparticulate therapies was approved by FDA and other agencies [31], with Doxil® (liposomal doxorubicin) being the first approved nanopharmaceutical in 1995 [32]. Liposomes are self-assembled vesicles created from phospholipids and cholesterol in aqueous medium. They are composed from a lipid bilayer structure and contain an inner aqueous core [33]. Due to that, they can carry both hydrophilic and hydrophobic drugs, making them extremely versatile. In parenteral delivery they are oftentimes used to increase the therapeutic index and the same is possible when being delivered to the respiratory system. An example is Curosurf®, a liposomal poractant alfa preparation (Chiesi) for treatment of acute respiratory distress syndrome. It is administered by instillation and allows increased delivery with smaller volume, while at the same time showing decreased toxicity compared to non-liposomal delivery [34].