Particulate bioaerogels for respiratory drug delivery

Abstract

The bioaerogel microparticles have been recently developed for respiratory drug delivery and attract fast increasing interests. These highly porous microparticles have ultralow density and hence possess much reduced aerodynamic diameter, which favour them with greatly enhanced dispersibility and improved aerosolisation behaviour. The adjustable particle geometric dimensions by varying preparation methods and controlling operation parameters make it possible to fabricate bioaerogel microparticles with accurate sizes for efficient delivery to the targeted regions of respiratory tract (i.e. intranasal and pulmonary). Additionally, the technical process can provide bioaerogel microparticles with the opportunities of accommodating polar, weak polar and non-polar drugs at sufficient amount to satisfy clinical needs, and the adsorbed drugs are primarily in the amorphous form that potentially can facilitate drug dissolution and improve bioavailability. Finally, the nature of biopolymers can further offer additional advantageous characteristics of improved mucoadhesion, sustained drug release and subsequently elongated time for continuous treatment on-site. These fascinating features strongly support bioaerogel microparticles to become a novel platform for effective delivery of a wide range of drugs to the targeted respiratory regions, with increased drug residence time on-site, sustained drug release, constant treatment for local and systemic diseases and anticipated better-quality of therapeutic effects.

Keywords: Amorphous form; Bioaerogel particulate platform; Improved aerosolisation performance; Targeted respiratory drug delivery; Ultralow densities.

Graphical abstract

Fig. 1

The size and morphology of BAMs fabricated by different technologies. IP: (A) Overall size/surface morphology and (B) Cross section of alginate-based BAMs (bar = 10 μm) [69] (Adapted with permission of Elsevier); EG: (C) Representative alginate-HA BAMs (bar = 100 μm) [70] (Adapted with permission from Elsevier), (D) Representative chitosan-alginate BAMs [72] (Reprinted with permission from MDPI under open-access policy, with modification), (E) Representative cellulose BAMs (bar = 10 μm) [76] (Adapted with permission from American Chemical Society); MD: (F) Egg white BAMs generated by spraying (bar = 20 μm) and (G) Whey protein BAMs fabricated by HG (bar = 100 μm) [75] (Adapted with permission from MDPI under open-access policy).

Fig. 2

The technical process to prepare drug-loaded BAMs for respiratory drug delivery. This figure was created by an author (H.Y.Li) with the support of BioRender (https://app.biorender.com).

Fig. 3

The gelation mechanisms for polysaccharides and proteins. Electrostatic interaction: A) The negative charged alginate chains interacted with positively charged calcium ions to form ‘egg-box’ structure for gelation, B) The negative charged alginate chains interacted with positively charged chitosan chains to form a gel; pH: C) Protonated chitosan neutralized by base and D) Alkalized cellulose neutralized by acid, to be jellified; Heat: E) Thermal-sensitive proteins denatured and jellified by heat. This figure was created by an author (H.Y.Li) with the support of BioRender (https://app.biorender.com).

Fig. 4

Anticipated processes and mechanisms for drug adsorption to BAMs. A) Drug adsorption processes into BAMs, which is derived from the typical adsorption processes reported somewhere else [104,105], where the microCT bioaerogel structure was adapted from [110] with permission from Elsevier; B) Proposed mechanisms for drug adsorption onto the skeletons of BAMs, derived from [105,107,108]. This figure was created by an author (H.Y.Li) with the support of BioRender (https://app.biorender.com).

Fig. 5

The responses of alveolar macrophage for the elimination of inhaled particles with different sizes. A) The schematic presentation to show the elimination of particles by alveolar macrophages through different processes, including (i) macrophage phagocytosis and intracellular digestion for small particles (d_v = 0.5–10 μm) and (ii) macrophage fusion to form MGCs for the engulfment of big particles (d_v = 10–100 μm) followed by intracellular digestion (Adapted from [146] with the permission from Frontiers under open-access policy); B) and C) Adapted fluorescence and optical microscopy images to show the MGC formed via alveolar macrophage fusion after the lungs exposed to the inhaled particles of cerium dioxide [147] and crocidolite asbestos [148] respectively (Reprinted with permission from Elsevier). This figure was created by an author (H.Y.Li) with the support of BioRender (https://app.biorender.com).

Fig. 6

Prospective functions associated with BAMs for respiratory drug delivery. This figure was created by an author (H.Y.Li) with the support of BioRender (https://app.biorender.com).