Abstract
Polyhydroxyalkanoates (PHA) are polyesters produced intracellularly by many bacterial species as energy storage materials, which are used in biomedical applications, including drug delivery systems, due to their biocompatibility and biodegradability. In this study, we evaluated the potential application of this nanomaterial as a basis of inhaled drug delivery systems. To that end, we assessed the possible interaction between PHA nanoparticles (NPs) and pulmonary surfactant using dynamic light scattering, Langmuir balances, and epifluorescence microscopy. Our results demonstrate that NPs deposited onto preformed monolayers of DPPC or DPPC/POPG bind these surfactant lipids. This interaction facilitated the translocation of the nanomaterial towards the aqueous subphase, with the subsequent loss of lipid from the interface. NPs that remained at the interface associated with liquid expanded (LE)/tilted condensed (TC) phase boundaries, decreasing the size of condensed domains and promoting the intermixing of TC and LE phases at submicroscopic scale. This provided the stability necessary for attaining high surface pressures upon compression, countering the destabilization induced by lipid loss. These effects were observed only for high NP loads, suggesting a limit for the use of these NPs in pulmonary drug delivery.
Highlights
The therapeutic efficacy of inhaled nanoparticles depends on their ability to cross the extracellular and cellular defensive barriers imposed by the lungs
The surface activity of pulmonary surfactant is characterized by three essential properties that have to be exhibited during respiration: (i) rapid adsorption at the air/alveolar fluid interface of the material secreted by type II pneumocytes and its transfer to the interface during inhalation, forming a surface-active film; (ii) reorganization of the interfacial film during the interfacial compression that occurs at exhalation, which allows properly packing, further reducing surface tension at the interface to extremely low values and thereby preventing the collapse of alveoli; and (iii) efficient spreading of packed lipids to redistribute laterally during the expansion of the air/liquid interface on subsequent inhalation [2,3,4]
Dynamic light scattering was used to evaluate the possible interaction of PHA nanoparticles with different components of pulmonary surfactant since this technique allows the study of the formation of lipid and protein coronas on nanomaterials [30,31]
Summary
The therapeutic efficacy of inhaled nanoparticles depends on their ability to cross the extracellular and cellular defensive barriers imposed by the lungs. In this sense, the nanoparticles that reach the alveoli first meet the interfacial layers of pulmonary surfactant, a lipoprotein complex that covers the alveolar epithelium and constitutes the first line of defense against inhaled entities. Pulmonary surfactant is composed of 90% lipids, dipalmitoylphosphatidylcholine (DPPC) being the main phospholipid species This lipid is characterized by saturated acyl chains, which allow it to pack tightly at the air/liquid interface, producing maximum reduction of surface tension at the end of exhalation and stabilization of open lungs [2]
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