Medicated ocular bandages and corneal health: potential excipients and active pharmaceutical ingredients.

Corneal blindness can occur due to improper healing of the corneal tissues after induced injury or abrasion which can be accidental, pathogenic, or after corneal surgery. Abnormal regulation of the healing mechanisms can lead to corneal opacity. Reducing inflammation and promoting epithelial wound healing are crucial for scar-free corneal recovery without eyesight complications. Current approaches for corneal wound healing involve amniotic membrane (AM) bandages, bandage contact lenses (BCL), and collagen shields in conjunction with frequent administration of therapeutic eye drops. The problem with eye drops is poor bioavailability and patient incompliance that might lead to corneal wound healing complications and poor clinical outcomes. Various methods have been proposed for loading drugs into medicated bandage lenses. There are advantages and limitations associated with each technique regarding the ease of manufacture, drug loading, release kinetics, and suitability with various therapeutics and hydrogel types. There is still, however, no drug-eluting corneal bandage on the market despite the need for such a convenient and cost-efficient strategy for corneal wound healing. This review will highlight materials and therapeutics that can be used in medicated ocular bandages and various ways of incorporating drugs, while discussing the limitations and challenges associated with bringing medicated ocular bandages in the market.

3D-Printed Hybrid Collagen/GelMA Hydrogels for Tissue Engineering Applications.

Bioprinting is an emerging technology involved in the fabrication of three-dimensional tissue constructs for the repair and regeneration of various tissues and organs. Collagen, a natural protein found abundantly in the extracellular matrix of several tissues, can be extracted from collagen-rich tissues of animals such as sheep, cows, rats, pigs, horses, birds, and marine animals. However, due to the poor printability of collagen bioinks, biocompatible collagen scaffolds that mimic the extracellular matrix (ECM) are difficult to fabricate using bioprinting techniques. Gelatin methacrylate (GelMA), a semi-synthetic polymer with tunable physical and chemical properties, has been found to be a promising biomaterial in various bioprinting applications. The printability of collagen can be improved by combining it with semi-synthetic polymers such as GelMA to develop hybrid hydrogels. Such hybrid hydrogels printed have also been identified to have enhanced mechanical properties. Hybrid GelMA meshes have not previously been prepared with collagen from ovine sources. This study provides a novel comparison between the properties of hybrid meshes with ovine skin and bovine hide collagen. GelMA (8% w/v) was integrated with three different concentrations (0.5%, 1%, and 2%) of bovine and ovine collagen forming hybrid hydrogels inks that were printed into meshes with enhanced properties. The maximum percentage of collagen suitable for integration with GelMA, forming hybrid hydrogels with a stable degradation rate was 1%. The water-soluble nature of ovine collagen promoted faster degradation of the hybrid meshes, although the structural crosslinking was identified to be higher than bovine hybrid meshes. The 1% bovine collagen hybrid meshes stood out in terms of their stable degradation rates.

An estriol-eluting pessary to treat pelvic organ prolapse.

Pelvic organ prolapse affects up to 50% of parous women. Commonly used treatment options have unwelcome attributes; pessaries can cause erosion and estrogen creams need to be applied frequently, which is inconvenient and difficult to administer. This study involved the development of an estriol-releasing pessary utilising 3D printing molds. We incorporated varying amounts of estriol (1%, 10% and 15%) into the silicone pessary. We optimised the mechanical aspects of the pessary so it had a similar strength to commercially available pessaries. We investigated estriol release from the pessary over 3 months. We explored possible interactions between the drug and polymers via FTIR. The MED-4870 silicone ring with similar mechanical strength to pessaries currently used to treat pelvic organ prolapse. The medical pessaries present a sustained release in simulated vaginal fluid over 3 months. The pessary with 10% estriol delivered the optimal dose at 0.8 mg each week. Mechanical strength of this pessary showed no difference after emersion in simulated vaginal fluid for 3-month, supporting the long-term application. An estriol-loaded pessary was successfully developed to treat pelvic organ prolapse with sustained release of estriol over 3 months. This pessary provides promising potential to treat pelvic organ prolapse and vaginal atrophy.

Gelatine-based drug-eluting bandage contact lenses: Effect of PEGDA concentration and manufacturing technique.

Drug-eluting bandage contact lenses (BCLs) have been widely studied as an alternative to eye drops due to their ability to increase the drug residence time and bioavailability as well as improve patient compliance. While silicone hydrogel polymers are commonly used in drug-eluting BCLs due to their transparency, mechanical properties and high oxygen permeability, gelatine hydrogels are also clear, flexible and have high oxygen permeability and may therefore be suitable contact lens materials. Moreover, the rheological properties of gelatine hydrogels allow their use as inks in extrusion-based 3D printers, therefore opening the door to a wide range of applications. Drug-loaded gelatine methacryloyl (GelMA) BCLs with different concentrations of poly (ethylene glycol) diacrylate (PEGDA) were prepared using solvent casting and 3D printing. The prepared lenses were characterised for their swelling ratio, in vitro degradation, and drug release properties. The results showed that the incorporation of 10% PEGDA improved the lenses' resistance to handling and protected them during degradation testing, reduced the swelling ratio and prolonged the release of dexamethasone (DEX). Both techniques were deemed suitable to use in the manufacturing of drug-eluting BCLs noting that the optimal formulation may vary according to the preparation technique utilised.

Ophthalmic gels: Past, present and future.

Aqueous gels formulated using hydrophilic polymers (hydrogels) along with those based on stimuli responsive polymers (in situ gelling or gel forming systems) continue to attract increasing interest for various eye health-related applications. They allow the incorporation of a variety of ophthalmic pharmaceuticals to achieve therapeutic levels of drugs and bioactives at target ocular sites. The integration of sophisticated drug delivery technologies such as nanotechnology-based ones with intelligent and environment responsive systems can extend current treatment duration to provide more clinically relevant time courses (weeks and months instead of hours and days) which will inevitably reduce dose frequency, increase patient compliance and improve clinical outcomes. Novel applications and design of contact lenses and intracanalicular delivery devices along with the move towards integrating gels into various drug delivery devices like intraocular pumps, injections and implants has the potential to reduce comorbidities caused by glaucoma, corneal keratopathy, cataract, diabetic retinopathies and age-related macular degeneration. This review describes ophthalmic gelling systems with emphasis on mechanism of gel formation and application in ophthalmology. It provides a critical appraisal of the techniques and methods used in the characterization of ophthalmic preformed gels and in situ gelling systems along with a thorough insight into the safety and biocompatibility of these systems. Newly developed ophthalmic gels, hydrogels, preformed gels and in situ gelling systems including the latest in the area of stimuli responsive gels, molecularly imprinted gels, nanogels, 3D printed hydrogels; 3D printed devices comprising ophthalmic gels are covered. Finally, new applications of gels in the production of artificial corneas, corneal wound healing and hydrogel contact lenses are described.