Nanotechnology strategies for the encapsulation, pulmonary delivery and alveolar macrophage targeting of rifampicin

ANDRADE F.; DAS NEVES J.; FERREIRA D.; CHIAPPETTA D.A.; LANGENHEIM M.; MORETTON M.A.; SOSNIK A.; SARMENTO B.

Porto

Congreso; IX Spanish-Portuguese Conference on Controlled Drug Delivery and III Congress of the Portuguese Society of Pharmaceutical Sciences "New Trends in Pharmaceutical Sciences"; 2011

Portuguese Society of Pharmaceutical Sciences, Universidad de Sevilla

Rifampicin (RIF) is a first-line antibiotic used in the treatment of tuberculosis (TB). According to the Biopharmaceutical Classification System (BCS), RIF is classified into Class II drugs (low aqueous solubility and high permeability), even if its reclassification into Class IV (low aqueous solubility and low permeability) has been recently recommended. The intrinsic water solubility fluctuates from 1 to 3 mg/mL at pH values between 3 and 7.4. The design of drug delivery systems localized in lung using polymeric nanocarriers loaded with antituberculosis drugs has emerged as a promising technology strategy to decrease the frequency of administration and doses, reduce systemic adverse effects and improve the therapeutic efficacy. However, the nanoparticles used must provide an aerodynamic diameter suitable for allowing the arrival and deposition in the lower respiratory tract after inhalation. In this context, the use of mucoadhesive polymers could improve the retention of the nanoparticles and extend the residence time, maximizing the release in the respiratory tract. This study will discuss the preliminary results of RIF encapsulation in chitosan nanoparticles, cellular uptake of NPs and RIF in macrophages, and their aerosolization pattern.