Chitosan nanoparticles laden contact lenses for enzyme-triggered controlled delivery of timolol maleate: A promising strategy for managing glaucoma.

To improve drug bioavailability, eye drops can be replaced by drug-eluting contact lenses. However, issues of drug leaching from lenses during manufacture and storage, and sterilization, currently limit their commercial application. To address the issues, stimuli-(lysozyme)-sensitive chitosan nanoparticles were developed to provide controlled ocular drug delivery. Nanoparticles were prepared by ionic gelation and characterized by TEM, X-ray diffraction, DSC, and FTIR. In the flux study, conventional-soaked contact lenses (SM-TM-CL) showed high-burst release, while with direct drug-only laden contact lenses (DL-TM-CL) the drug was lost during extraction and sterilization, as well as having poor swelling and optical properties. The nanoparticle-laden contact lenses (TM-Cht-NPs) showed controlled release of timolol for 120 h in the presence of lysozyme, with acceptable opto-physical properties. In the shelf-life study, the TM-Cht-NPs contact lenses showed no leaching or alteration in the drug release pattern. In animal studies, the TM-NPs-CL lenses gave a high drug concentration in rabbit tear fluid (mean = 11.01 µg/mL for 56 h) and helped maintain a low intraocular pressure for 120 h. In conclusion, the chitosan nanoparticle-laden contact lenses demonstrated the potential application to treat glaucoma with acceptable opto-physical properties and addressed the issues of drug-leaching during sterilization and storage.

In vitro and in vivo evaluation of cyclosporine-graphene oxide laden hydrogel contact lenses.

Drug-eluting contact lens can substitute the multiple eye drop therapy. However, loading hydrophobic drug like cyclosporine in the contact lens is very challenging, due to low drug uptake (via soaking method); and alteration in the swelling and optical properties which restricts its clinical application. To address the above issues, graphene oxide (GO, large surface area with oxygen containing functional groups) was incorporated in the contact lenses during fabrication. These GO-laden contact lenses (SM-GO-Cys) as well as blank contact lenses (SM-Cys) were soaked in the solution of cyclosporine. Alternatively, cyclosporine-laden contact lenses (DL-Cys-20) and cyclosporine-GO-laden contact lenses (DL-Cys-20-GO) were fabricated by adding drug and drug-GO (at various level of GO) during fabrication, respectively. Contact angle and swelling data showed increase in water holding capacity of GO laden contact lenses. Optical property was significantly improved due to molecular dispersion of drug on the surface of GO sheets. The drug uptake and in vitro release profile was improved with GO-laden contact lenses by soaking method (SM-GO-Cys-400n) due to hydrophobic interactions between GO and drug. Adding cyclosporine-GO (DL-Cys-20-GO-800n) during fabrication significantly improved drug release kinetics with higher drug leaching (during extraction and sterilization) due to increased swelling, improved dissolution and molecular dispersion of drug on GO sheets. Ocular irritation and histopathological studies demonstrated the safety of GO-contact lens. The in vivo drug release studies in the rabbit eye showed significant improvement in mean residence time (MRT) and area under the curve (AUC) using DL-Cys-20-GO-800n contact lens compared to eye drop solution with reduction in protein adherence value. The study demonstrated that the incorporation of GO into the contact lens can control the release of cyclosporine as well as improved the lens swelling and transmittance properties.

Recent advances in ophthalmic preparations: Ocular barriers, dosage forms and routes of administration.

The human eye is a complex organ with unique anatomy and physiology that restricts the delivery of drugs to target ocular tissues/sites. Recent advances in the field of pharmacy, biotechnology and material science have led to development of novel ophthalmic dosage forms which can provide sustained drug delivery, reduce dosing frequency and improve the ocular bioavailability of drugs. This review highlights the different anatomical and physiological factors which affect ocular bioavailability of drugs and explores advancements from 2016 to 2020 in various ophthalmic preparations. Different routes of drug administration such as topical, intravitreal, intraocular, juxtascleral, subconjunctival, intracameral and retrobulbar are discussed with their advances and limitations.

Advances and challenges in the nanoparticles-laden contact lenses for ocular drug delivery.

The delivery of drugs that target ocular tissues is challenging due to the physiological barriers of the eye like tear dilution, nasolacrimal drainage, blinking, tear turnover rate and low residence time Drug-laden contact lenses can be a possible solution to overcome some of these challenges. Nanoparticles are being extensively studied as novel systems for loading drugs into therapeutic contact lenses. The versatile features of the organic and inorganic nanoparticles and their diverse physicochemical properties make it possible to load and sustain drug release from the contact lenses. Nevertheless, several issues remains to be solved before its clinical application and commercialization such as changes in contact lens swelling (water content), transmittance, protein adherence, surface roughness, tensile strength, ion and oxygen permeability and drug leaching during contact lens manufacture. However, clinical studies demonstrated the potential of therapeutic contact lenses to manage the scientific, commercial and regulatory challenges to make its place in the market. This review highlights the different methodologies used to fabricate nanoparticle-laden contact lenses and highlights the major advances and challenges to commercialization.