A promising 'single' and 'dual' drug-nanocomposite enriched contact lens for the management of glaucoma in response to the tear fluid enzyme.

Glaucoma is a neurodegenerative condition that results in the damage of retinal ganglion cells due to elevated intraocular pressure (IOP). To curtail the limitations associated with conventional treatments such as eye drops and ocular suspensions, we have developed 'single' and 'dual' drug delivery contact lenses (CLs), that is, latanoprost (LP) and latanoprost-timolol (LP-TM) deliverable CLs, in response to lysozyme (Lyz), which is abundant in the lacrimal fluid. Since chitosan (CS) can entrap more of the drug and also undergo hydrolysis in the presence of Lyz, we have employed CS for the composite preparation. The CL fabrication was performed by free radical copolymerization of poly(2-hydroxyethyl methacrylate) (pHEMA) in the presence of the drug-loaded nanocomposite with UV-curing initiators using the pre-drug loading strategy. The surface morphological, optical and mechanical investigations confirmed the presence of the drugs, ≥80% transparency, the adequate flexibility and biocompatibility of both the CLs. The in vitro release experiments showed the release of 95.86% LP from LP-CL, and 83.87% LP and 86.70% TM from LP-TM-CL in the presence of 1.5 mg mL-1 of Lyz in 72 h. In vitro biocompatibility assay against human corneal epithelial (HCE) cells and ex vivo experiments on HET-CAM confirmed that the fabricated LP-CL and LP-TM-CL are well tolerated. Moreover, in vivo safety evaluations of CLs on New Zealand white rabbit eyes suggest no sign of irritation to the ocular tissues within 72 h of observation. Hence, the study suggests that the 'single' and 'dual' drug-loaded CLs could open a new avenue to manage glaucoma by maintaining mean diurnal IOP.

Development of mucoadhesive Timolol loaded chitosan-nanocomposite to treat glaucoma.

Timolol Maleate is an aqueous soluble ß-blocker antiglaucoma drug used to suppress intraocular pressure. Several commercially available ocular formulations are not effective in delivering to the target site due to their water-soluble property and low mucoadhesiveness. Hence, there is a requirement for a highly mucoadhesive drug-loaded nanocomposite to suppress intraocular pressure with enhanced bioavailability. Herein, we have prepared a mucoadhesive Timolol-loaded graphene quantum dot-chitosan-nanocomposite to treat glaucoma in response to lysozyme, secreted in the tear fluid. The as-prepared nanocomposite has been characterized through high resolution-transmission electron microscopic, X-ray photoelectron spectroscopic, X-ray diffraction, and Fourier transform infrared spectral studies. The nanocomposite showed 93.74 % encapsulation efficiency with a loading capacity of 7.73 %. Further, 89.26 %, 95.62 %, and 99.29 % of drug release were observed from the nanocomposite in the presence of 1, 1.5, and 2 mg/mL of lysozyme. The mucoadhesion property has been confirmed by the increment in the particle size, fluorescence spectral variations, and Fourier transform infrared spectroscopic studies in the presence of mucin nanoparticles of size 291 nm. Interestingly, mucoadhesion has been demonstrated by pointing to the quenching in the luminescence of mucin. Further, in vitro biocompatibility assay on human corneal epithelial cells showed ≥80 % cell viability. Hence, this study offers the utilization of naturally secreting enzymes for drug delivery applications instead of uncontrolled pH and temperature-triggered releases.

Novel chitosan - graphene quantum dots composite for therapeutic delivery and tracking through enzymatic stimuli response.

The designing of highly efficient and biocompatible nanocomposites with multifunctional delivery and tracking characteristics is noteworthy for clinical and therapeutic applications. Herein, we report the proof-of-concept for the delivery of anti-glaucoma drug, latanoprost (LP) under an enzymatic stimulus, lysozyme (Lyz) with novel chitosan (CS) - graphene quantum dots (GQD) nanocomposite via reverse switching photoluminescence (PL) phenomenon. The LP caged CS-GQDs nanocomposite was well characterized through extensive spectral, morphological, band-gap, particle size, and zeta potential studies along with cytotoxicity assays. The regaining of PL not only confirmed LP delivery, but also facilitated intercellular tracking through in vitro bio-imaging against human corneal epithelial (HCE) cells. The AO/EB staining and biocompatibility assays further proved excellent cell viability of >80%. The successfully delivered LP protected HCE cells from oxidative injury induced by 800 µM hydrogen peroxide (H2O2). These findings justify further utility of novel CS-GQDs caged drug nanocomposite for preclinical investigations.