Banca de DEFESA: EMANUELLA CHIARA VALENÇA PEREIRA

DEVELOPMENT OF ANTI-INFLAMMATORY PHARMACEUTICAL FORMULATIONS BASED ON HSPT@ZIF-8

Inflammation, flavonoids, MOFs, pharmaceutical suspensions

Hesperetin is a product of secondary plant metabolism, classified as a flavonoid and has
several activities reported in the literature as antioxidant, antibacterial, antiviral,
neuroprotective, anticancer, chemopreventive and, most notably, anti-inflammatory. In
order to be used as a drug, hesperetin needed to have its dissolution rate improved from
the development of the modified release system HSPT@ZIF-8 using MOF ZIF-8 as
carrier. This work aimed to conduct a literature review on the use of MOFs as
pharmaceutical excipients and the development of a pharmaceutical formulation using
the HSPT@ZIF-8 system with anti-inflammatory activity. Thus, a literature review was
carried out using international databases (PubMed, Scopus, ScienceDirect and Web of
Science) showing that MOFs are promising materials for biomedical application,
including their use as drug carriers capable of modulating the release of pharmaceuticals.
To initiate the development of the formulation, the acute in vivo oral toxicity of the
HSPT@ZIF-8 system was evaluated. Then, aqueous-based pharmaceutical suspensions
containing the HSPT@ZIF-8 system, isolated hesperetin and ZIF-8 as active principle
were developed. The suspensions were submitted to organoleptic evaluation, hesperetin
content, pH, viscosity, redispersability, morphological analysis by microscopy and also
to the evaluation of anti-inflammatory activity through the in vivo model of paw edema
induced by carrageenan. The pharmaceutical suspensions showed good quality
parameters such as pleasant color, odor and taste, pH compatible with the stability of the
active ingredient, being easily redispersible and without cake formation and with
pseudoplastic rheological behavior already expected for this type of formulation. The oral
acute toxicity test demonstrated that the HSPT@ZIF-8 system is safe under these
conditions up to a maximum dosage of 2000mg/Kg. In the evaluation of the antiinflammatory
activity in vivo, the anti-inflammatory activity expected by hesperetin was
demonstrated, however, it was noted that it is independent of the dose. It was
demonstrated that the HSPT@ZIF-8 system presented anti-inflammatory activity
superior to that of isolated hesperetin, it was also demonstrated that the placement of the
system in a pharmaceutical suspension did not alter its anti-inflammatory activity. Thus,
this work showed that MOFs can be great alternatives to be used as pharmaceutical
excipients in obtaining modified drug delivery systems. A pharmaceutical suspension
containing the HSPT@ZIF-8 system as active ingredient was developed, which presented
good quality parameters and anti-inflammatory activity superior to isolated hesperetin.