Encapsulation of isoniazid into alginate particles using a microfluidic device

MENGATTO, L.; BERLI C.L.A.; OLIVARES, M.L.; MARENGO, R.C.

Córodoba

Congreso; II Brazil-Argentine Microfluidics Congress; 2019

Universidad Nacional de Córdoba

Microfluidics allows preparingmonodisperse particles with controlled shape and size.  These particles are used as protective shellsof active ingredients and to control the release of entrapped molecules. Tuberculosis(TB) is an infectious disease usually caused by Mycobacterium tuberculosis. Isoniazid (INH) is one of the first-line antibiotics recommended for thetreatment of TB. The adverse effects related to INH (particularly itshepato-toxicity) may result in lack of compliance by the patients and in theinterruption of treatment. This situation has serious consequences for thecontrol of the disease. INH is associated with rifampicin (RIF) as a combinedregimen of antibiotic treatment. RIF hydrolyzes in acidic medium and in thepresence of INH, its rate of degradation increases. The aim of the current work wasto develop a microfluidic-based process for the preparation of alginateparticles containing INH.  The entrapmentmight help to reduce adverse effects caused by INH and to increase the stabilityof RIF in the presence of INH. Microfluidic chips were made in PMMA by lasermicromachining. The microchannel network integrates two successivecross-junctions to generate double emulsions. Flow rates Q were controlled bysyringe pumps. The following fluids were injected at each inlet port (see theattached figure, middle panel): aqueous solution of sodium alginate (2 % w/w)containing 0.2% w/v of INH (Q = 0.5 mL/h), olive oil (Q = 3.0 mL/h), andcalcium chloride (2 % w/w) dissolved in a polyvinyl acetate solution (Q = 1.0mL/h).  In order to prepare particleswith a high degree of cross-linking, the emulsions obtained in the outlet port werecollected in a 3 % w/w calcium chloride solution. Observations carried out byoptical microscopy showed that particles were spherical in shape (315 ± 57 um).The drug release into PBS buffer (pH =7) was quantified by HPLC. The release profile of the microparticles presented an initial burstphase, where more than 20% of the INH was released during the first 24 h. Then,the curve slope decreases and reaches a maximum (50%) at about 50 h. It isconcluded that the studied microfluidic method was suitable for the generationof microparticles capable to encapsulate and release INH.