Improving ocular bioavailability of hydrophilic drugs through dynamic covalent complexation.

The clinical benefits of diquafosol tetrasodium (DQS), a hydrophilic P2Y2 receptor agonist for dry eye, have been hindered by a demanding dosing regimen. Nevertheless, it is challenging to achieve sustained release of DQS with conventional drug delivery vehicles which are mainly designed for hydrophobic small molecule drugs. To address this, we developed an affinity hydrogel for DQS by taking advantage of borate-mediated dynamic covalent complexation between DQS and hydroxypropyl guar. The resultant formulation (3% DQS Gel) was characterized by sustained release, low corneal permeation, and extended ocular retention, which were desirable attributes for ocular surface drug delivery. Both in vitro and in vivo studies had been carried out to verify the biocompatibility of 3% DQS Gel. Using corneal fluorescein staining, the Schirmer's test, PAS staining, quantitative PCR and immunohistological analyses as outcome measures, the superior therapeutic effects of 3% DQS Gel over PBS, the hydrogel vehicle and free DQS were demonstrated in a mouse dry eye model. Our DQS delivery strategy reported herein is readily applicable to other hydrophilic small molecule drugs with cis-diol moieties, thus providing a general solution to improve clinical outcomes of numerous diseases.

A ratiometric water-soluble fluorescent probe for the detection of sulfur dioxide derivative in sinusitis mice model.

Sulfur dioxide (SO2) plays an extremely important role in the basic processes of physiology and pathology. As an antioxidant, SO2 can maintain the redox homeostasis in the cell. Excessive inhalation of SO2 would lead to irreparable respiratory damage, resulting in respiratory diseases, neurological disorders, and even cardiovascular disease. Thus, it is urgent to exploit an excellent way to monitor SO2 derivatives in biological system. Herein, we design a water-soluble ratiometric fluorescent probe to fast detect the level of SO2 derivatives in living cells in vivo. The probe displays obvious fluorescence signal at long wavelength, which is helpful for imaging of biological system. After respond to SO2 derivatives, the fluorescence signal at 465 nm increases rapidly due to the Michael addition reaction is triggered, further causing the disruption of large conjugated system. The probe exhibits high selectivity and fast respond to SO2 derivatives, which can be able to sensitive and real-time monitoring of SO2 derivatives level in living cells. Moreover, the probe reveals a low detection limit and a great linear relationship to SO2 derivatives. Based on the negligible cytotoxicity and good biocompatibility of the probe, which is employed to detect exogenous and endogenous SO2 derivatives in living cells. In addition, it is also served as a potential chemical tool to detect SO2 derivatives in mice model of sinusitis.