RESUMO
This study presents a quantitative assessment of the complexation between boronic acids and diols as a reversible and double-stimulus (oxidation and acidification)-responsive bioconjugation reaction. First, by using a competition assay, we have evaluated the equilibrium constants (water, pH 7.4) of 34 boronate/diol pairs, using diols of both aliphatic and aromatic (catechols) nature; in general, catechols were characterized by constants 3 orders of magnitude higher than those of aliphatic diols. Second, we have demonstrated that successful complexation with diols generated in situ via enzymatic reactions, and the boronate complexation was also employed to calculate the Michaelis-Menten parameters for two catechol-producing reactions: the demethylation of 3-methoxytyramine and the 2-hydroxylation of estradiol, respectively, mediated by P4502D6 and P4501A2. Third, we have prepared phenylboronic acid-functionalized hyaluronic acid (HA) and demonstrated the pH and H2O2-responsive character of the adducts that it formed with Alizarin Red S (ARS) used as a model catechol. The versatility and selectivity of the complexation and the mild character of the chemical species involved therefore make the boronate/catechol reaction an interesting candidate for bioconjugation purposes.
Assuntos
Antraquinonas/química , Ácidos Borônicos/química , Catecóis/química , Dopamina/análogos & derivados , Estradiol/química , Antraquinonas/metabolismo , Ácidos Borônicos/metabolismo , Catecóis/metabolismo , Cromatografia de Afinidade , Dopamina/química , Dopamina/metabolismo , Estradiol/metabolismo , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/metabolismo , Oxirredução , Água/química , Água/metabolismoRESUMO
Punctal plugs (PPs) are miniature medical implants that were initially developed for the treatment of dry eyes. Since their introduction in 1975, many PPs made from different materials and designs have been developed. PPs, albeit generally successful, suffer from drawbacks such as epiphora and suppurative canaliculitis. To overcome these issues intelligent designs of PPs were proposed (e.g. SmartPLUG™ and Form Fit™). PPs are also gaining interest among pharmaceutical scientists for sustaining drug delivery to the eye. This review aims to provide an overview of PPs for dry eye treatment and drug delivery to treat a range of ocular diseases. It also discusses current challenges in using PPs for ocular diseases.
