Nebulizing novel multifunctional nanovesicles: the impact of macrophage-targeted-pH-sensitive archaeosomes on a pulmonary surfactant

Altube, María Julia; Cutró, Andrea Carmen; Bakás, Laura Susana; Morilla, María José; Disalvo, E.A.; Romero, Eder Lilia

doi:10.1039/c7tb01694h

Cited by 18 publications

(10 citation statements)

References 60 publications

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“…The order and fluidity of nanovesicles bilayers were assessed by determining GP and FA of Laurdan respectively, according to [25]. Briefly, nanovesicles were labelled with Laurdan by mixing 10 l of 120 mM Laurdan in methanol with a volume of nanovesicles sufficient to render a 1:20 mol:mol Laurdan:lipids ratio.…”

Section: Laurdan Generalized Polarization (Gp) and Fluorescence Anisomentioning

confidence: 99%

“…Another interesting property is the natural targeting ability of certain ARC, that depends on the type of lipids produced by different archaebacteria gender [24]. Specifically, ARC made of archaeolipids from Halorubrum tebenquichense contain PGP-Me, a ligand for scavenger receptors class A (SRA1) [25] highly expressed on macrophages and dendritic cells. Such naturally targeted ARC thus, facilitate the endocytic uptake of carried payload by macrophages with no aid of complex chemical derivatization [26,27].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Superoxide dismutase in nanoarchaeosomes for targeted delivery to inflammatory macrophages

Schilrreff

Simioni

Jerez

et al. 2019

Colloids and Surfaces B: Biointerfaces

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Section: Laurdan Generalized Polarization (Gp) and Fluorescence Anisomentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Superoxide dismutase in nanoarchaeosomes for targeted delivery to inflammatory macrophages

Schilrreff

Simioni

Jerez

et al. 2019

Colloids and Surfaces B: Biointerfaces

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“…As depicted in Figure 3 , IMQ did not modify nanovesicles bilayers fluidity that showed identical FA before and after IMQ loading. IMQ on the other hand, did not affect the order of LIPO bilayers, but deeply reduced the typical high disorder of ARC bilayers (Altube et al, 2017 ); the trend followed by the GP values was: nanoARC-IMQbc> nanoARC-IMQ (finished formulation) > ARC. The GP of the more ordered nanoARC-IMQbc bilayer was reduced after washing loosely trapped IMQ in nanoARC-IMQ; in other words, the order decreased as IMQ was removed.…”

Section: Resultsmentioning

confidence: 99%

“…The effect of IMQ on fluidity and order of nanoARC-IMQ and LIPO-IMQ bilayers was assessed according to Altube et al ( 2017 ). To that aim, the fluorescent probe of membrane structure, sensitive to the solvent relaxation effect Laurdan was employed to determine generalized polarization (GP) and fluorescence anisotropy (FA), respectively.…”

Section: Resultsmentioning

confidence: 99%

Make It Simple: (SR-A1+TLR7) Macrophage Targeted NANOarchaeosomes

Parra

Caimi

Altube

et al. 2018

Front. Bioeng. Biotechnol.

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Hyperhalophilic archaebacteria exclusively produce sn2,3 diphytanylglycerol diether archaeolipids, unique structures absent in bacteria and eukaryotes. Nanovesicles made of archaeolipids known as nanoarchaeosomes (nanoARC), possess highly stable bilayers, some of them displaying specific targeting ability. Here we hypothesize that nanoARC made from Halorubrum tebenquichense archaebacteria, may constitute efficient carriers for the TLR7 agonist imiquimod (IMQ). NanoARC-IMQ takes advantage of the intense interaction between IMQ and the highly disordered, poorly fluid branched archaeolipid bilayers, rich in archaeol analog of methyl ester of phosphatidylglycerophosphate (PGP-Me), a natural ligand of scavenger receptor A1 (SR-A1). This approach lacks complex manufacture steps required for bilayers labeling, enabling future analytical characterization, batch reproducibility, and adaptation to higher scale production. SR-A1 mediated internalization of particulate material is mostly targeted to macrophages and is extensive because it is not submitted to a negative feedback. A massive and selective intracellular delivery of IMQ may concentrate its effect specifically into the endosomes, where the TLR7 is expressed, magnifying its immunogenicity, at the same time reducing its systemic bioavailability, and therefore it's in vivo adverse effects. NanoARC-IMQ (600–900 nm diameter oligolamellar vesicles of ~−43 mV Z potential) were heavily loaded with IMQ at ~44 μg IMQ/mg phospholipids [~20 folds higher than the non-SR-A1 ligand soyPC liposomes loaded with IMQ (LIPO-IMQ)]. In vitro, nanoARC-IMQ induced higher TNF-α and IL-6 secretion by J774A1 macrophages compared to same dose of IMQ and same lipid dose of LIPO-IMQ. In vivo, 3 subcutaneous doses of nanoARC-IMQ+ 10 μg total leishmania antigens (TLA) at 50 μg IMQ per Balb/C mice, induced more pronounced DTH response, accompanied by a nearly 2 orders higher antigen-specific systemic IgG titers than IMQ+TLA and LIPO-IMQ. The isotype ratio of nanoARC-IMQ+TLA remained ~0.5 indicating, the same as IMQ+TLA, a Th2 biased response distinguished by a pronounced increase in antibody titers, without negative effects on splenocytes lymphoproliferation, with a potential CD8+LT induction 10 days after the last dose. Overall, this first approach showed that highly SR-A1 mediated internalization of heavily loaded nanoARC-IMQ, magnified the effect of IMQ on TLR7 expressing macrophages, leading to a more intense in vivo immune response.

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“…DPPC has been well researched and employed for developing liposomal inhalation suspensions for targeted lung delivery and interventions including penetration of biofilms and uptake into macrophages (Chimote and Banerjee, 2010;Zhang et al, 2018). In addition, endogenous lung surfactant inspired strategies including phospholipid based nanovesicle aerosols (Joshi et al, 2015;Altube et al, 2017;Parra et al, 2018) have been reported as pulmonary compatible and efficient drug delivery platforms.…”

Section: The Hypothesis and The Discussionmentioning

confidence: 99%

Co-aerosolized Pulmonary Surfactant and Ambroxol for COVID-19 ARDS Intervention: What Are We Waiting for?

Kumar

2020

Front. Bioeng. Biotechnol.

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After more than 225 days of the first reports of the novel coronavirus from China, COVID-19 pandemic is still on surge. The search for an effective and efficient therapeutic and pharmaceutical intervention is as important and urgent now as it was on Day 1. Majority of the efforts in this direction are toward finding small molecule interventions via repurposing or redirecting the therapeutic approaches. This hypothesis proposes a physical intervention approach directed toward rescuing the complex lung pathology observed in COVID-19 related acute respiratory distress syndrome (CARDS). The loss of content as well as the synthesis and turnover of the surfactant in ARDS has been termed as a "collateral damage." A synergistic, early stage, cost-effective, pharmaceutically viable, safe, and immediately available solution is hence required. The effectiveness of exogenous surfactant treatment in ARDS has been marred with several limitations as pointed out in various clinical trials and require revised protocols related to surfactant dose and mode of delivery. This hypothesis proposes aerosolized surfactant delivery taking the optimal dosing and coating costs into account along with co-delivery of ambroxol to provide synergistic benefits. Ambroxol is reported to have anti-inflammatory,-oxidant,-viral, and-bacterial activities and has a direct impact on the production and secretion of the surfactant from the alveolar Type 2 cells. If aerosolized, atomized, or nebulized in the form of ambroxol-loaded phospholipid nanovesicles at the early stages of ARDS, depleted surfactant levels may be reinstated and surfactant turnover can be initiated and maintained. The ability to deliver both the components in aerosolized-nebulized form may have a huge impact on alleviating the healthcare burden in low resource settings where the availability of ventilators is limited. In conclusion, the surfactant-ambroxol co-aerosolized intervention approach hypothesized here has implications reaching to clinical and pharmaceutical translation worldwide.

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Nebulizing novel multifunctional nanovesicles: the impact of macrophage-targeted-pH-sensitive archaeosomes on a pulmonary surfactant

Abstract: Novel nebulized pH-sensitive nanovesicles remain structurally stable after crossing the pulmonary surfactant monolayer and could release a cytoplasmic fluorophore marker into the underlying macrophages.

Cited by 18 publications

References 60 publications

Superoxide dismutase in nanoarchaeosomes for targeted delivery to inflammatory macrophages

Superoxide dismutase in nanoarchaeosomes for targeted delivery to inflammatory macrophages

Make It Simple: (SR-A1+TLR7) Macrophage Targeted NANOarchaeosomes

Co-aerosolized Pulmonary Surfactant and Ambroxol for COVID-19 ARDS Intervention: What Are We Waiting for?

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