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.

Amino acid conjugated chitosan nanoparticles for the brain targeting of a model dipeptidyl peptidase-4 inhibitor.

Saxagliptin (SAX) is a dipeptidyl peptidase-4 enzyme inhibitor molecule now explored for its activity in the therapy of Alzheimer's disease. Being extremely hydrophilic, it is unable to permeate the blood-brain barrier by the conventional therapy modalities. Further repurposing the drug, SAX is associated with a reduction in the blood sugar level in the periphery. In the present study, the chitosan-l-valine conjugate was synthesized by carbodiimide chemistry. The conjugate was then used to prepare nanoparticles encapsulating SAX. The nanoparticles were characterized by particle size, surface morphology, and entrapment efficiency. The stability of the formulations was determined by incubation with rat plasma and brain homogenate. The blood brain barrier permeability of the nanoparticles was successfully demonstrated by the incorporation of fluorescent dye, Rhodamine B in the nanoparticles. In vivo studies were conducted in rats and the results showed that the nanoparticles were highly stable in the plasma releasing only a minute amount of SAX (2.5 ng/mL) which was less than the Cmax of the pure SAX (51 ng/mL). The brain uptake studies showed an accumulation of 53 ng/mL SAX from the nanoparticles whereas the pure SAX showed no detectable amount of the drug after 24 h. The pharmacokinetic studies demonstrated that nanoparticles had an (AUC0-t) of 3.42 times lower than the pure SAX, indicating the stability of the prepared formulation in the plasma.