Mucoadhesive thermogel platform for treating anterior ocular conditions

Abstract

A platform mucoadhesive and thermogelling eyedrop was developed for application to the inferior fornix for the treatment of various anterior segment ocular conditions. The poly(n-isopropylacrylamide) polymers (pNIPAAm), containing a disulfide bridging monomer, were crosslinked with chitosan to yield a modifiable, mucoadhesive, and natively degradable thermogelling system. Three different conjugates were studied including a small molecule for treating dry eye, an adhesion peptide for modeling delivery of peptides/proteins to the anterior eye, and a material property modifier to create gels with different rheologic characteristics. Based on the conjugate used, different material properties such as solution viscosity and lower critical solution temperature (LCST) were produced. In addition to releasing the conjugates through disulfide bridging with ocular mucin, the thermogels were shown to deliver atropine, with 70%-90% being released over 24-h, depending on the formulation studied. The results illustrate that these materials can deliver multiple therapeutic payloads at one time and release them through various mechanisms. Finally, the safety and tolerability of the thermogels was demonstrated both in vitro and in vivo. The gels were instilled into the inferior fornix of rabbits and were shown to not produce any adverse effects over 4 days. These materials were demonstrated to be highly tunable, creating a platform that could be easily modified to deliver various therapeutic agents to treat a multitude of ocular diseases and have the potential to be an alternative to conventional eyedrops.

FOF1-ATPase Motor-Embedded Chromatophore as Drug Delivery System: Extraction, Cargo Loading Ability and Mucus Penetration Ability

“…This is especially important in delivering actives with large molecules [ 1 ] such as proteins, peptides and vaccines [ 2 ]. These mucosal cargo delivery systems could be prepared with versatile formulations and then administered through multiple non-invasive routes such as nasal ones [ 3 ], oral ones [ 4 , 5 ], the eye [ 6 ], the gastrointestinal tract, airways [ 7 ] and the vagina. These routes could be applied both for systemic drug administration and for local treatment of mucosal diseases [ 8 ].…”