Sahar Awwad

• UCL

A 2-compartment in vitro eye flow model has been developed to estimate ocular drug clearance by the anterior aqueous outflow pathway. The model is designed to accelerate the development of longer-acting ophthalmic therapeutics. Dye studies show aqueous flow is necessary for a molecule injected into the vitreous cavity to clear from the model. The c...

The eye is a highly specialised organ that is subject to a huge range of pathology. Both local and systemic disease may affect different anatomical regions of the eye. The least invasive routes for ocular drug administration are topical (e.g. eyedrops) and systemic (e.g. tablets) formulations. Barriers that subserve as protection against pathogen e...

The majority of blinding conditions arise due to chronic pathologies in the retina. During the last two decades, antibody-based medicines administered by intravitreal injection directly into the back of the eye have revolutionised the treatment of chronic retinal diseases characterised by uncontrolled blood vessel growth, e.g. wet age-related macul...

New in vitro prototypes (PK-Eye™) were tested with and without eye movement to understand diffusion and convection effects on intraocular clearance. Port placement in front ((i) ciliary inflow model) and behind the model lens ((ii) posterior inflow model) was used to study bevacizumab (1.25 mg/50 µL) and dexamethasone (0.1 mg/100 µL) in phosphate-b...

Real-time measurement is important in modern dissolution testing to aid in parallel drug characterisation and quality control (QC). The development of a real-time monitoring platform (microfluidic system, a novel eye movement platform with temperature sensors and accelerometers and a concentration probe setup) in conjunction with an in vitro model...

We previously described FpFs 1̲ (Fab–PEG–Fab) as binding mimetics of IgGs.

Inkjet printing has the potential to advance the treatment of eye diseases by printing drugs on demand onto contact lenses for localised delivery and personalised dosing, while near-infrared (NIR) spectroscopy can further be used as a quality control method for quantifying the drug but has yet to be demonstrated with contact lenses. In this study,...

Knowledge of drug mass transfer from the anterior chamber via the iris-lens barrier has important implications for the development of front of the eye medicines that can also deliver drugs to the vitreous cavity. Here, the design and evaluation of a novel in vitro model that studies anterior clearance kinetics is reported. To mimic some aspects of...

Dry eye disease is a common ocular disorder that is characterised by tear deficiency or excessive tear evaporation. Current treatment involves the use of eye drops; however, therapeutic efficacy is limited because of poor ocular bioavailability of topically applied formulations. In this study, digital light processing (DLP) 3D printing was employed...

Highlights • Dual acting therapeutic proteins may be a better strategy than drug combinations for treatment of chronic retinal diseases. •Several targets to treat neovascularisation and inflammation have been identified. •A dual acting molecule to increase the duration of action in the vitreous has potential for treatment of chronic retinal diseas...

Proteins and peptides have emerged in recent years to treat a wide range of multifaceted diseases such as cancer, diabetes and inflammation. The emergence of polypeptides has yielded advancements in the fields of biopharmaceutical production and formulation. Polypeptides often display poor pharmacokinetics, limited permeability across biological ba...

Lipidised analgesic peptide prodrugs self-assemble into peptide nanofibers; with the nanofiber morphology protecting the peptide from plasma degradation and improving therapeutic efficacy. Extending this learning, we hypothesised that a self-assembling lipidized peptide arginine vasopressin (AVP) receptor agonist, that had not been designed as a pr...

Conjugation by bis-alkylation using latently cross-conjugated reagents is a basis for site-specific PEGylation to the two cysteine thiols derived from a native disulfide. Known as disulfide bridging PEGylation, bis-alkylation can also be used to target histidine imidazole residues allowing for His-tag–selective PEGylation at either the N- or C-term...

Intravitreal injections have become the cornerstone of retinal care and one of the most commonly performed procedures across all medical specialties. The impact of hydrodynamic forces of intravitreal solutions when injected into vitreous or vitreous substitutes has not been well described. While computational models do exist, they tend to underesti...

Therapeutic protein medicines have transformed the treatment of blinding diseases (e.g. age-related macular degeneration, AMD) during the last 1–2 decades. Many blinding conditions such as AMD are chronic; and require multiple intravitreal injections over a long period to achieve a high and reproducible dose needed for clinical benefit. Prolonging...

RNA interference induced by double-stranded, small interfering RNA (siRNA) molecules has attracted great attention as a naturally-occurring approach to silence gene expression with high specificity. The Myocardin-Related Transcription Factor/Serum Response Factor (MRTF/SRF) pathway is a master regulator of cytoskeletal gene expression and thus repr...

Monoclonal antibodies (mAbs) are one of the most important classes of therapeutic proteins, which are used to treat a wide number of diseases (e.g., oncology, inflammation and autoimmune diseases). Monoclonal antibody technologies are continuing to evolve to develop medicines with increasingly improved safety profiles, with the identification of ne...

Many limitations of protein-based medicines have been shown clinically to be alleviated by the covalent conjugation of poly(ethylene glycol) (PEG) in a process known as protein PEGylation. There are at least 15 registered PEGylated products with more in clinical development. Protein PEGylation is generally used to extend the protein circulation tim...

Injectable gels have the potential to encapsulate drugs for sustained release of protein therapeutics for use in the eye. Hyaluronic acid (HA) is a biodegradable clinically used material and poly N-isopropylacrylamide (pNIPAAM) is a stimuli responsive polymer that can display a lower critical solution temperature (LCST) at physiological conditions....

Biotechnology harnesses cellular and biochemical systems to advance knowledge of the molecular cause of disease and to provide new diagnostic tools and more precisely targeted drugs. Within a decade, global investment in medical biotechnology has increased more than ten-fold, resulting in therapies for previously untreatable conditions. But what ex...

Statement of significance: Bevacizumab is a potent protein drug which is highly effective in the treatment of degenerative conditions in the eye. To be effective, frequent injections into the eye are required, which is deeply unpleasant for patients and expensive for healthcare providers. Alternative methods of administration are thus greatly soug...

There is a need to prolong drug residence time using a biocompatible formulation in the subconjunctival space after surgery to treat glaucoma. Drug releasing discs were prepared with 2-(hydroxyethyl)methacrylate (HEMA) and 2-methacryloyl- oxyethyl phosphorylcholine (MPC). The ratio of bound water (Wb) to free water (Wf) ratio increased from 1:0.3 t...

Corticosteroids have long been used to treat intraocular inflammation by intravitreal injection. We describe dexamethasone loaded poly-DL-lactide-co-glycolide (PLGA) microparticles that were fabricated by thermally induced phase separation (TIPS). The dexamethasone loaded microparticles were evaluated using a two-compartment, in vitro aqueous outfl...

Prolonging therapeutic levels of a drug within the vitreous to treat blinding diseases is one of the most important goals in ophthalmic drug development. Intravitreal (IVT) injections of therapeutic proteins and the use of steroid implants in the vitreous cavity are currently the best clinical methods to achieve prolonged exposure in the back of th...

This chapter outlines the developing applications for polymeric materials in nanopharmacy and pharmaceutical science, and some of the opportunities for, and also barriers against, the use of macromolecules and conjugates as therapeutics. It is also important to consider some recent routes by which polymers can be made to controlled chain lengths an...

An ageing population, together with a greater understanding of ocular disease, are driving the development of new generations of protein therapeutics for ocular use. Currently, antibodies to treat age related macular degeneration (AMD) are administered about every 4-6 weeks by intravitreal (IVT) injections. Although IVT injections are generally saf...

Two series of fibers containing the active ingredients acyclovir, ciprofloxacin and cyanocobalamin, and combinations of these drugs, were prepared by electrospinning. One set used the hydrophilic poly(vinylpyrrolidone) (PVP) as the filament-forming polymer, while the other used the slow-dissolving poly(ε-caprolactone) (PCL). The fibers were found t...