Design, optimization, and in vivo assessment of in situ pH-sensitive quercetin transbilosomes for the treatment of diabetes mellitus-associated heart failure

Quercetin (QCT) is an effective flavonoid that offers protection against diabetes mellitus-associated heart failure (HF) due to its antioxidant properties. The effectiveness of QCT is, however, constrained by its low bioavailability and poor solubility. An in-situ pH-sensitive formulation of QCT-loaded transbilosomes (IPSQLT) was developed for nasal administration. This formulation aims to enhance sustainability, bioavailability, permeability, and the effectiveness of QCT in treating diabetes-associated HF. To determine the optimal QLT formulation, various formulations were developed using the Box-Behnken design. The IPSQLT formulation was developed by incorporating an optimal QLT formulation along with chitosan and glyceryl monooleate. The in vivo study employed an experimental diabetes and HF-induced rat model to evaluate the bioavailability and effectiveness of the IPSQLT formulation. The IPSQLT formulation enhanced QCT's sustainability, permeability, and bioavailability by 60.64%, 7.11 times, and 7.37 times, respectively, compared to free QCT. The nasal IPSQLT formulation significantly reduced levels of glucose, LDH, CK-MB, troponin-1, and MDA compared to the positive control group, with reductions of 92.52%, 97.89%, 93.22%, 97.60%, and 98.79%, respectively. Additionally, IPSQLT elevated the levels of GSH, SOD, and CAT by 3.41-fold, 3.13-fold, and 3.13-fold, respectively. These findings suggest that nasal IPSQLT could serve as a potential treatment option for diabetes-associated heart failure.