Benznidazole in vitro dissolution release from a pH-sensitive drug delivery system using Zif-8 as a carrier

Abstract

Chagas disease is a neglected tropical disease caused by the flagellate protozoan Trypanosoma cruzi (T. cruzi). Endemic in underdeveloped and developed countries, due to the migratory movement, it is considered a serious public health problem. Endemic in underdeveloped countries and due to the migratory movement, in developed countries as well, it is considered a serious public health problem. One of the reasons for this is a weak therapeutic arsenal, represented only by the drug benznidazole (BNZ) which, although it promotes significant cure rates in the acute phase of the disease, presents serious problems of toxicity and bioavailability, mainly due to its low aqueous solubility. Several studies have presented several drug delivery systems (DDS) based on BNZ aiming at enhancing its solubility in aqueous medium and, with this, promoting an increase in the dissolution rate and, consequently, in its bioavailability. However, the present work is a pioneer in using a zeolitic imidazolate framework as a carrier agent for a DDS in order to promote a pH-sensitive modulation of the drug. Thus, this work aimed to develop a novel DDS based on BNZ and the ZIF-8 to use it in development of prolonged-release dosage forms to alternative treatment of Chagas disease. The BNZ@ZIF-8 system was obtained through an ex situ method selected due to its higher incorporation efficiency (38%). Different characterization techniques corroborated the obtainment and drug release data were analyzed by in vitro dissolution assay under sink and non-sink conditions and setting the kinetic results through both model dependent and independent methods. Under sink conditions, at pH 4.5, BNZ and BNZ@ZIF-8 showed similar release profile, but the DDS was effective in promoting a prolonged release. At pH 7.6, after 7 h, BNZ showed a lower release than BNZ@ZIF-8. On the other hand, in non-sink conditions at pH 4.5 the BNZ presented 80% of drug release in 3 h, while the DDS in 6 h. At pH 7.6, BNZ presented a release of 80% in 2 h, while the DDS reaches it in only at 12 h. Therefore, at pH 4.5 the DDS BNZ@ZIF-8 showed a faster release with a burst effect, while at pH 7.6 it showed a prolonged and controlled release. Finally, it is evident that a promising DDS pH-sensitive was obtained as a novel carrier that might be able to prolongs BNZ release in dosage forms intended for the alternative treatment of Chagas disease.

Anti-blastocystosis activity of antioxidant coated ZIF-8 combined with mesoporous silicas MCM-41 and KIT-6

“…The ZIF-8 nanocarrier with pH sensitivity has been reported to be beneficial against parasite protozoan Trypanosoma infection. At acidic pH of 4.5, a quick release of benznidazole was observed, while the trend changes to a sustained and longer release at pH 7.4 38 . In our case, the hydroxyl functionalization of curcumin and resveratrol with nanocomposites may be critical in protonation and might assist such release in acidic pH condition.…”

Targeted Delivery of Gemcitabine for Precision Therapy of Cholangiocarcinoma Using Hyaluronic Acid-Modified Metal–Organic Framework Nanoparticles

“…Therefore, it is worthwhile to investigate the specific release behavior of GEM by constructing a pH-responsive delivery system based on ZIF-67. Due to its pH-sensitive dissolution properties, ZIF-67 has been applied in pH-controlled drug release systems. , This study aimed to determine whether GEM@ZIF-67-HA NPs exhibit pH-responsive release of GEM. The pH in tumor tissue (5.5–6.0) is usually lower than the pH in normal tissue (7.4).…”

“…Due to its pH-sensitive dissolution properties, ZIF-67 has been applied in pH-controlled drug release systems. 26 , 27 This study aimed to determine whether GEM@ZIF-67-HA NPs exhibit pH-responsive release of GEM. The pH in tumor tissue (5.5–6.0) is usually lower than the pH in normal tissue (7.4).…”

Alternative Approaches for the Treatment of Chagas Disease

“…Ferraz et al . (2021 and 2020) utilized ZIF‐8 and BNZ as carriers to develop medication delivery devices sensitive to changes in pH, respectively, showing controlled and prolonged release of BNZ under varying pH conditions [176–177] . In 2020, Silva et al .…”