@article {18907,
	title = {Magneto-responsive gelatin microparticulate systems for targeted pulmonary delivery of anti-tuberculosis drugs},
	booktitle = {Chem2Nature First School},
	year = {2016},
	month = {2016-11-21 00:00:00},
	address = {Avepark, Guimar{\~a}es, Portugal},
	abstract = {

Tuberculosis (TB) remains one of the major health problems worldwide despite the fact that treatment regimens are available. The airways are the principal route of infection that initiates when Mycobacterium tuberculosis (Mtb) bacilli are inhaled and phagocytized by alveolar macrophages.

In the past few years, inhalable microparticulate drug delivery systems in dry powder form have emerged as an innovative and promising alternative to target delivery of drugs directly to the alveoli milieu and/or infected macrophages, with potential to significantly improve the therapeutics efficiency and reduce undesirable side effects. Moreover, magnetic nanoparticles have been investigated for remotely controlled drug delivery strategies, including targeting of MNPs and triggered release under the influence of a magnetic field.[1]

Thus, the goal of this work was to develop magneto-responsive microparticulate systems (MPs) for pulmonary delivery of a new anti-TB drug, a purine derivative (P3), which demonstrated high in vitro anti-TB activity. MPs are envisioned to carry and delivery P3 drug into lung alveoli and infected macrophages for the treatment of TB.

Calcium carbonate sacrificial templates were used as a {\textquotedblleft}cast{\textquotedblright} strategy to produce monodisperse MPs composed of a gelatin shell filled with gelified bovine serum albumin. Superparamagnetic iron oxide nanoparticles (SPIONs) were also incorporated in the MPs for triggered drug release upon actuation of an alternate magnetic field (AMF). The MPs were characterized in terms of aerodynamic diameter (fluctuability into the lower airways), geometric diameter (to be phagocytosed by the macrophages) and P3 loading efficiency and release profile at different pH (physiological and lysosomal: 5.4) and upon AMF actuation (30min, 3mT, 1000Hz).

The developed MPs present features that enable the potential delivery of the drug to the lower pulmonary airways, without inducing cytotoxicity. The release profile of P3 from the MPs can be triggered at different pHs, with an increased release at pH 5.4. Moreover, the P3 release can be remotely modulated by the actuation of an AMF. MPs and P3-MPs evidence no cytotoxic effect on L929 cells with P3 loads up to 5IC90. Overall, the developed MPs present unique and promising features as drug delivery systems aiming at a more efficient treatment of tuberculosis.

[1]\ \ \ \  Hauser, A.K., et al., Magnetic nanoparticles and nanocomposites for remote controlled therapies. J Control Release, 2015. 219: p. 76-94.

Acknowledgments: M.S. Miranda thanks Funda{\c c}{\~a}o para a Ci{\^e}ncia e a Tecnologia (FCT) the postdoctoral scholarship (SFRH/BPD/110868/2015) and Recognize project (UTAP-ICDT/CTM-BIO/0023/2014).

}, keywords = {dry powder, Magnetic nanoparticles, microparticles, tuberculosis}, author = {Miranda, M. S. and Domingues, R. M. A. and Rodrigues, M. T. and Costa, R. R. and Gon{\c c}alves, C. and Carvalho, A. and Reis, R. L. and Pedrosa, J. and Gomes, M. E.} }

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