Trojan particles: Large porous carriers of nanoparticles for drug delivery

Abstract

We have combined the drug release and delivery potential of nanoparticle (NP) systems with the ease of flow, processing, and aerosolization potential of large porous particle (LPP) systems by spray drying solutions of polymeric and nonpolymeric NPs into extremely thin-walled macroscale structures. These hybrid LPPs exhibit much better flow and aerosolization properties than the NPs; yet, unlike the LPPs, which dissolve in physiological conditions to produce molecular constituents, the hybrid LPPs dissolve to produce NPs, with the drug release and delivery advantages associated with NP delivery systems. Formation of the large porous NP (LPNP) aggregates occurs via a spray-drying process that ensures the drying time of the sprayed droplet is sufficiently shorter than the characteristic time for redistribution of NPs by diffusion within the drying droplet, implying a local Peclet number much greater than unity. Additional control over LPNPs physical characteristics is achieved by adding other components to the spray-dried solutions, including sugars, lipids, polymers, and proteins. The ability to produce LPNPs appears to be largely independent of molecular component type as well as the size or chemical nature of the NPs. L arge porous particles (LPPs), characterized by geometric sizes larger than 5 m and mass densities around 0.1 g͞cm 3 or less, have achieved recent popularity as carriers of drugs to the lungs for local and systemic applications (1, 2). A principal advantage of LPPs relative to conventional inhaled therapeutic aerosol particles is their aerosolization efficiency (3, 4); in addition, LPPs possess the potential for avoidance of alveolar macrophage clearance (5-7), enabling sustained drug release in the lungs (8).Particles with geometric diameters less than a few hundred nanometers (9) represent an even more tenacious resident of the lungs. Once deposited, nanoparticles (NPs) or ''ultrafine'' particles often remain in the lung lining fluid until dissolution (assuming they are soluble), escaping both phagocytic and mucociliary clearance mechanisms (5-8). Thus, deposition of drug-bearing NPs in the lungs may offer the potential for sustained drug action and release throughout the lumen of the lungs, not only in the deep lung or alveolar region, where macrophage clearance occurs. However, the utility of NPs for drug release is severely limited because of their low inertia, which causes them to be predominantly exhaled from the lungs after inspiration (10, 11). Moreover, their small size leads to particleparticle aggregation, making physical handling of NPs difficult in liquid and dry powder forms; this is a common practical problem that must be overcome before using NPs for oral drug delivery (12, 13). As a result of these limitations, NPs are not presently being explored commercially or clinically as vehicles for drug delivery in the lungs.We have developed a form of particle for drug delivery that combines the advantages of LPPs and NPs while avoiding their limitations. We use spray drying (14) to form...

Dynamics of Surfactant-Driven Fracture of Particle Rafts

“…Understanding the means by which fractures occur and the dynamics of their propagation in these systems may have very real benefits in, for example, stabilising foams, drops and bubbles by the addition of particles. One particularly interesting possibility lies in the delivery of drugs by inhalation, where trojan parcels of drugs in drops are coated with particulate rafts [6]. Our work suggests that the delivery process might be expedited by using the surfactant lining of the lungs to induce the rupture of the particle shell.…”

“…Similarly, the addition of particles to the surface of liquid drops prior to coalescence stabilises the coalesced drops to the common pinch-off instability and can lead to reversible morphological instabilities such as buckling when subject to pressure [3]. Particle covered interfaces also occur at an intermediate stage during the production of colloidosomes [4], armored bubbles [5] and porous particle aerosols for drug delivery [6]. From both a fundamental and technological point of view these particulate interfaces pose a number of problems and opportunities.…”

Microparticles and nanoparticles for drug delivery

“…It is possible to confer the advantages of one class of vehicle on another by combining them. This approach has been used with microparticles in a gel , nanoparticles in a cross-linked hydrogel matrix (Yeo et al, 2006b), and nanoparticles in aerodynamically superior microparticles (Tsapis et al, 2002).…”

The indentation of pressurized elastic shells: from polymeric capsules to yeast cells

“…Much of the early work focused on axisymmetric geometries but more recently the simple problem of indentation has been used as a starting point in understanding some of the more complicated geometries that arise when an object with an intrinsic curvature is subject to different external loads [16,17]. By contrast, very little work has concerned the indentation of a pressurized elastic shell, despite its technological importance in applications such as pressure vessels [18] or capsules designed for drug delivery [19,20]. However, numerical simulations have been carried out for the case of a thick, fluid-filled shell with a constant volume [21] and for a thin shell (or membrane) subject to a constant internal pressure [20].…”