muramidase and Glaucoma

Most of the people in the world are affected by glaucoma, which leads to irreversible blindness. Several patient friendly treatments are available, nevertheless medications lack an easy and efficient way of sustained delivery. To make the delivery with enhanced bioavailability, biodegradable and non-biodegradable polymers-based drug carriers are explored. However, ocular drug delivery issues have not been resolved yet due to less adhesiveness, poor penetration ability, pH, and temperature dependent burst releases. Chitosan is found to be effective for ocular drug delivery due to excellent physio-chemical properties in terms of overcoming the existing issues. In this review, we aim to highlight why it has been chosen and the holy grail for ocular drug delivery. Besides, we have comprehensively reviewed recent patents on chitosan as a platform for ocular drug delivery and future perspectives on factors, lacunae and challenges that need to be addressed for better ocular delivery methods for glaucoma management.

Topics: Administration, Ophthalmic; Biocompatible Materials; Chitosan; Contact Lenses; Corneal Injuries; Drug Carriers; Drug Delivery Systems; Glaucoma; Humans; Lubricant Eye Drops; Materials Testing; Microscopy, Electron, Scanning; Muramidase; Nanoparticles; Wetting Agents; Wound Healing

Timolol Maleate is an aqueous soluble β-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.

Topics: Chitosan; Drug Delivery Systems; Glaucoma; Humans; Mucins; Muramidase; Nanocomposites; Nanoparticles; Timolol

Temporarily implanted devices, such as drug-loaded contact lenses, are emerging as the preferred treatment method for ocular diseases like glaucoma. Localizing the delivery of glaucoma drugs, such as timolol maleate (TM), can minimize adverse effects caused by systemic administration. Although eye drops and drug-soaked lenses allow for local treatment, their utility is limited by burst release and a lack of sustained therapeutic delivery. Additionally, wet transportation and storage of drug-soaked lenses result in drug loss due to elution from the lenses. Here we present a nanodiamond (ND)-embedded contact lens capable of lysozyme-triggered release of TM for sustained therapy. We find that ND-embedded lenses composed of enzyme-cleavable polymers allow for controlled and sustained release of TM in the presence of lysozyme. Retention of drug activity is verified in primary human trabecular meshwork cells. These results demonstrate the translational potential of an ND-embedded lens capable of drug sequestration and enzyme activation.

Topics: Contact Lenses; Diamond; Drug Carriers; Drug Design; Glaucoma; Humans; Muramidase; Nanogels; Polyethylene Glycols; Polyethyleneimine; Polyhydroxyethyl Methacrylate; Timolol

The long-term effect of timolol maleate on lacrimal secretion was tested by investigating the concentration of lysozyme and albumin in tears before the start of treatment and after different follow-up periods. A total of 25 patients (45 eyes) were treated with 0.25% or 0.5% timolol as the only antiglaucomatous therapy over a 7.6 month mean observation period (2-13 months). No significant change was found either in the lysozyme or in the albumin concentration.

Topics: Adult; Aged; Albumins; Female; Glaucoma; Humans; Male; Middle Aged; Muramidase; Propanolamines; Tears; Timolol