According to the World Health Organization (WHO) neglected diseases (ND) afflict the lives of one billion people in the world. Tuberculosis is a ND, being the leading cause of death in the world. Isoniazid (INH) is one of the most commonly used antibiotics in the treatment of tuberculosis. The present study synthesized a nanocarrier for INH using expanded perlite as an alternative source of silica to obtain the precursor for NPS synthesis by the modified Stober method (sol-gel process). The optimization of NPS synthesis of different size (178.8 to 559.1 nm) and size distribution (mono and bimodal) was performed, presenting an excellent synthesis efficiency (99.79%) and fast (without many steps, complicated apparatus or reagents of high toxicity) and easy to perform. The experimental design was used to optimize the INH incorporation process in NPS, with the optimal conditions of INH incorporation: 0.075 mg/mL, pH 2, 24 h and 600 mg of nanocarrier (NPS). The pH-dependent system of INH + NPS was promising to improve the bioavailability and consequent better absorption of INH, since it ensured a more efficient release in intestinal pH and with a larger fraction of non-ionized molecules due to the resulting interaction between INH and NPS.