Organic Salts Based on Isoniazid Drug: Synthesis, Bioavailability and Cytotoxicity Studies

Abstract

Tuberculosis is one of the ten causes of morbidity and mortality worldwide caused by Mycobacterium tuberculosis complex. Some of the anti-tuberculosis drugs used in clinic studies, despite being effective for the treatment of tuberculosis, present serious adverse effects as well as poor bioavailability, stability, and drug-resistance problems. Thus, it is important to develop approaches that could provide shorter drug regimens, preventing drug resistance, toxicity of the antibiotics, and improve their bioavailability. Herein, we reported the use of organic salts based on the isoniazid drug, which can act as an organic cation combined with suitable organic anions such as alkylsulfonate-based (mesylate, R or S-Camphorsulfonate), carboxylate-based (glycolate, vanylate) and sacharinate. The synthesis, characterization, and cytotoxicity studies comparing with the original isoniazid drug have been performed. The possibility to explore dicationic salts seems promising in order to improve original bioavailability, and promote the elimination of polymorphic forms as well as higher stability, which are relevant characteristics that the pharmaceutical industry pursues.

Breaking barriers: The potential of nanosystems in antituberculosis therapy

“…The primary metabolic process for isoniazid is acetylation [ 191 ]. Its elimination half-life, including that of its metabolites, varies between 0.5 and 4 h. The primary excretion route is renal, with 75–96 % of the drug and its metabolites expelled in urine within 24 h [ 192 ]. Conversely, the challenge with RIF bioavailability is its combined administration with fixed doses of other anti-TB drugs.…”

“…This protonation action prevents adequate pharmacological absorption, reducing its therapeutic potential. This occurs because ionized INH shows a decrease in their lipid solubility and therefore an inability to efficiently cross the cell membrane, which can lead to the implementation of high daily dosage regimens to ensure therapeutic efficacy [ 335 , 336 ]. In this context, Almeida et al [ 337 ] used MSNs to improve the bioavailability and provide INH controlled release.…”

Enhanced In Vitro Antiviral Activity of Hydroxychloroquine Ionic Liquids against SARS-CoV-2

“…In our group, we have developed API-OSILs based on several anionic or cationic drugs, including antibiotics [50][51][52][53][54][55], bone antiresorptive agents [56][57][58] and NSAIDs [59,60]. These can be considered novel ionic formulations of such drugs, which display enhanced water solubility and permeability, as well as reduced polymorphism, thus potentially leading to different pharmacokinetic and delivery profiles.…”