Microencapsulated lipid nanoparticles for pulmonary delivery of biopharmaceutical agents

A key point in the administration of biopharmaceuticals is the recognition of appropriate, effective, safe and biocompatible nanocarriers allowing overcoming extracellular and intracellular biological barriers without loss of drug stability and adequate therapeutic response at the target sites. Since their description by Rainer Müller in the early 1990’s, solid lipid nanoparticles (SLN) have been developed as an effective colloidal drug carrier. Under optimized conditions, SLN can be produced for the entrapment of lipophilic or hydrophilic drugs with the essential requirements for an optimum nanoparticulate carrier. Its colloidal size and the controlled release behaviour allow protection and management when administered by parenteral and non-parenteral routes (e.g., oral, nasal and pulmonary).

The pulmonary route has gained interest to the non-invasive administration of biopharmaceuticals on account of the promising anatomical features of the lung, particularly its large absorptive epithelial surface area, low thickness and avoiding the first-pass effect. The lung region where the particles are deposited depends on their aerodynamic diameter. The complex structure of the respiratory tree and the natural defence mechanisms of the lung are fundamental aspects for the design of a proper pulmonary delivery system.

Although pulmonary delivery of nanoparticles has an unquestionable interest, it still requires a complex setup and an aerosolization technique, due to their low inertia and small size, which hindering the deposition in the lung, facilitating the exhalation with air. A promising alternative is the formulation of nanoparticles in inhalable microspheres that ensure their release after pulmonary administration. Microspheres have recently been proposed for pulmonary inhalation as dry powders, since they can be designed to achieve appropriate morphological and aerodynamic characteristics. Previous studies have shown that polymeric nanocarriers loaded in microparticulate systems present a great potential for pulmonary delivery of therapeutic macromolecules and genetic material. These microspheres act only as inert vehicles of the nanoparticles, which remain unaltered after the spray-drying process, not affecting the properties or the release profile of the encapsulated active agents, thus constituting a suitable microparticulate carrier for the pulmonary delivery of drug-containing nanoparticles.


Thesis 2017 by Diana Patricia Rodrigues Gaspar
Microencapsulated lipid nanoparticles fo
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