Inhaled Micro- or Nanoparticles: Which are the Best for Intramacrophagic Antiinfectious Therapies?

Nanotechnology is a fascinating world that has provided and still provides sensational developments in many fields such as in pharmaceutics for diagnosis or drug and gene delivery to cells, tissues or organs. With regard to the latter, cell uptake of nanostructures (generally 1-100 nm) is usually much greater than that of microparticles in the range of 1-10 μm. Although the term “nano” remains ofhigh impact, not always the nanosize is preferable to a larger size. One of these cases is represented by the inhalation of drugs transported within particulate carrier in order to reach the Alveolar macrophages (AM) and eradicate surviving intracellular bacteria in pathologies such as tuberculosis, HIV, S. pneumoniae and S. aureus infections.

For an intra-macrophagic anti-infectious therapy by pulmonary administration, most antibiotics are poorly soluble in water and

their aerosolization has to be produced by using drugs in their solid state administered by means of Dry powder inhaler (DPI) devices. In this regard, it is rare that untreated drugs have features suitable for both DPI performance and targeting to AM failing to both reach alveolar epithelium and penetrate AM effectively. Therefore, particle engineering techniques have been proposed for both drug alone (micronization, polymorphic transformations, controlled crystallization, intermolecular self-assembling, spray-drying producing irregular shaped particles) and drug/excipient blending (with lactose or mannitol) or carrier-based formulations (liposomes, polymeric/lipid microparticles, cyclodextrins).

Various inhaled particulate carriers containing therapeutic agents have been used to deliver drugs to the AM leading to intracellular concentrations of the antibiotic up to 20-fold enriched compared to the administration of free drug . Particulate systems have also been engineered to facilitate uptake by macrophages or surface modified for receptor-mediated AM endocytosis.

Regarding particulate carrier-based formulations, among several other properties, particle size is crucial not only to guarantee effective dose emission by DPI, powder dispersion and deposition onto alveolar epithelium, but also effective endocytosis by AM that correlates with the efficacy of the loaded antimicrobial agents, i.e., the adequate local antibacterial concentration (>> MIC). The literature review shows several nanoparticle platforms for AM intracellular therapy. Read more..........