Mucoadhesive chitosan derivatives as novel drug carriers

Chitosan on its own is a well-established natural polymer and is widely regarded as a biodegradable, biocompatible and nontoxic material for drug delivery applications. Although unmodified chitosan has some mucoadhesive properties on its own, its bioavailability is limited due to its short retention time in the body. Moreover, the high solubility of chitosan at acidic pH levels limits its use for mucosal drug delivery (especially through the oral route). Chemically-modified mucoadhesive chitosan, especially thiolated chitosan, has arisen as an alternative to create novel mucosal drug delivery systems. The mucoadhesive properties that are conferred to the thiolated chitosan certainly set this novel class of second or third-generation thiomers apart. To understand the significance of mucoadhesive chitosan, we first present the mechanism of mucoadhesion and provide comprehensive coverage of description of a variety of chemical modifications to prepare mucoadhesive thiolated chitosan derivatives. We then present the plethora of applications of these modified chitosan variants in a wide range of drug delivery fields, including the delivery of antigens, proteins and genes through a variety of routes, including oral, nasal, pulmonary, vaginal and others. By presenting the range of applications for mucoadhesive chitosan drug carriers we herein demonstrate that chemically-modified thiolated chitosan is a versatile and effective material for a new class of drug delivery vehicles.Scopu

Resolution of MoS2 nanosheets-induced pulmonary inflammation driven by nanoscale intracellular transformation and extracellular-vesicle shuttles

Pulmonary exposure to some engineered nanomaterials can cause chronic lesions as a result of unresolved inflammation. Among two-dimensional (2D) nanomaterials and graphene, MoS2 have received tremendous attention in optoelectronics and nanomedicine. Here we propose an integrated approach to follow up the transformation of MoS2 nanosheets at the nanoscale and their impact on the lung inflammation status over one month after a single inhalation in mice. Analysis of immune cells, alveolar macrophages, extracellular vesicles, and cytokine profiling in bronchoalveolar lavage fluid (BALF) showed that MoS2 nanosheets induced initiation of lung inflammation that was rapidly resolved despite the persistence of various biotransformed molybdenum-containing nanostructures in alveolar macrophages and extracellular vesicles up to one month. Using in situ liquid phase transmission electron microscopy experiments, we could evidence the dynamics of MoS2 nanosheets transformation triggered by reactive oxygen species. Three main transformation mechanisms were observed directly at the nanoscale level: 1) scrolling of the dispersed sheets leading to the formation of nanoscrolls and folded patches, 2) etching releasing soluble MoO4-, and 3) oxidation generating oxidized sheet fragments. Extracellular vesicles released in BALF were also identified as a potential shuttle of MoS2 nanostructures and their degradation products and more importantly as mediators of inflammation resolution