Absence of lung fibrosis after a single pulmonary delivery of lipid nanocapsules in rats

Abstract

Lipid nanocapsules (LNCs) are potential drug carriers for pulmonary delivery since they can be nebulized without any structural or functional changes, and the aerosols produced are highly compatible with pulmonary drug delivery in human beings. The alveolar surface tension, in vitro cytotoxicity, biodistribution and pulmonary toxicity in rats of a single endotracheal spray of LNCs or paclitaxel-loaded LNCs were studied. In vitro cytotoxicity of LNCs after a spray remained unchanged. Biodistribution study showed a homogeneous repartition in the lungs in rats with an improvement in lung retention of the radiolabeled tracer loaded in LNCs compared to the absence of LNCs with a lung half-time of 8.8±0.7 hours. Bronchoalveolar fluid analysis revealed transient 7-day alveolar inflammation, reaching a maximum between days 2 and 4, characterized by a peak of granulocytes at day 1 followed by a peak of lymphocytes at day 3. Alveolar protein levels were increased at days 3 and 7. Acute inflammation was increased with paclitaxel-loaded LNCs in comparison with blank LNCs but dropped out at day 7. No histological pulmonary lesion was observed at day 60. LNCs lowered surface tension to a greater degree than Curosurf ® in a physicochemical model of the pulmonary alveolus. A single pulmonary delivery of LNCs induces a short-term alveolar inflammation with no residual lesions in rats at day 60. These data permit to start the study of LNCs in surfactant replacement therapy.

Carbohydrate-based Trojan microparticles as carriers for pulmonary delivery of lipid nanocapsules using dry powder inhalation

“…The size of the LNCs is in the low nanometric scale, typically between 20-100 nm. Among the LNCs, the nanocarriers with a size 50-60 nm have been the most widely studied thus far [10,15,16], hence they were selected for this work. In this work, LNCs composed of MHS (43.41%), hydrogenated lecithin (3.85%) and TGs (52.74%) were successfully prepared with a diameter of 59±3 nm and polydispersity index of 0.041±0.015, consistent with previous reports [10,15,18,19].…”

“…Among them, lipid nanocapsules (LNCs) are biomimetic nanocarriers that offer numerous advantages such as feasibility at laboratory or large scale, manufacturability via an organic solvent-free, low energy method, good physical stability, biocompatibility, possibility of surface modification [14][15][16][17][18].…”

<p>Di-<em>O</em>-lauroyl-decitabine-lipid nanocapsules: toward extending decitabine activity</p>

“…13 These nanoparticles have demonstrated great potential for the encapsulation of lipophilic drugs 14 and biopolymers. 15 Such nanomedicines show a good toxicity profile 16,17 and can be produced in large batches. 18 We were, thus, interested in encapsulating decitabine in these nanocarriers.…”