Acid-responsive nanospheres from an asparagine-derived amphiphile

Abstract

We describe the synthesis and self-assembly of an asparagine-derived amphiphile. The self-assembled systems formulated with the inclusion of cholesterol (0–50 mol%) show encapsulation for a hydrophobic model drug and rapidly disintegrate in response to mild acidic conditions.

Self-assembled nanospheres for encapsulation and aerosolization of rifampicin

“…As it can be observed in Fig. 3A, and in agreement with previous results, 12 spherical particles with rather uniform optical density were observed when only the NP was placed in the nebulizer. On the other hand, much smaller particles (solids) were obtained when a solution of RIF (no NP) was nebulized (Fig.…”

“…On the contrary, when the composite of NP/RIF was aerosolized, the expected core/shell arrangement was obtained (Figure 3C). In this case, the dimensions of neither the RIF core nor the lipidic shell were significantly affected (when compared to the originally described NP 12 ). It was observed however, that the RIF core visualized inside the NP were morphologically cubic.…”

“…Aiming to address these shortcomings, the present manuscript describes the encapsulation of RIF in self-assembled nanoparticles (NP) produced as aerosols using a low-cost, hand-held nebulizer. This communication builds on a previous report 12 focused on the development of the nanoparticles and their potential to encapsulate model drugs.…”

“…† NPs containing RIF were prepared according to a procedure recently described. 12 Briey, the lipid nanoparticle formulation was prepared by a combination acid responsive asparagine-derived amphiphile (ALA-11) and cholesterol (20 : 80). The N,N-acetal group of ALA-11 disassembles under acidic conditions resulting in the release of a hydrophobic encapsulate.…”

“…The use of nanomaterials 9 and colloidal systems 10 are promising avenues for decreasing side effects, enhancing the therapeutic efficacy, and improving bioavailability. 11,12 Because they exhibit unique physicochemical properties such as ultrasmall and controllable size, large surface-to-volume ratio, and well-known surface chemistry, 13 nanoparticles have been proposed for formulations administered via diverse delivery modalities including parenteral, oral, intraocular, transdermal, or pulmonary inhalation. As the latter route is non-invasive and can be used for both systemic and local applications, 7,14 it has received great attention in last few years.…”