Tuberculosis is caused by M. tuberculosis, which may attack mainly the lungs surviving within alveolar macrophages (AM). Pulmonary route appears the most promising way to reach promptly the infected site. To achieve effective drug delivery inside AM, drugs are required to reach alveoli and to be taken up by AM. In order to fulfil this goal, respirable powders of rifampicin loaded Solid Lipid Nanoparticle assemblies (SLNas) able to be internalized by AM were developed using the melt emulsifying technique and modifying conveniently pre-freezing parameters by means of Design of Experiments approach. The most favourable impact on powder respirability (>50% respirable fraction) was exerted by quick-freezing combined with a certain grade of sample dilution without the use of cryoprotectants [1, 2]. SLNas surface functionalization by methyl α-D-mannopyranoside (MP) recognizing mannose receptors located on infected AM was realized to facilitate cell internalization (active targeting). Mannosylated SLNas exhibited physical properties suitable for AM passive targeting, adequate rifampicin payloads (10-15%), and feasible drug maintenance within SLNas along the respiratory tract before AM internalization. Concerning the active targeting, the presence of MP on SLNas surface caused a quicker internalization rate by AM. Nevertheless, respirability was impaired by the powders cohesiveness . Therefore, novel more balanced amphiphiles bearing mannose residues differently arranged on SLNas surface were considered reaching improved respirability performance.
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|Data di pubblicazione:||2017|
|Autori:||Maretti, Eleonora; Iannuccelli, Valentina|
|Titolo:||PASSIVE AND ACTIVE TARGETING TO MACROPHAGES USING LIPID NANOPARTICLES ASSEMBLIES FOR ANTI-TB THERAPY BY PULMONARY ROUTE|
|Appare nelle tipologie:||Abstract in Atti di Convegno|
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