A5060355775- Glaucoma and retinal disorders
- Monoclonal and Polyclonal Antibodies Research
- Ocular Surface and Contact Lens
- Protein purification and stability
- Advanced Drug Delivery Systems
- Corneal Surgery and Treatments
- RNA Interference and Gene Delivery
- Retinal and Macular Surgery
- Dendrimers and Hyperbranched Polymers
- Retinal Diseases and Treatments
- Chemical Synthesis and Analysis
- Click Chemistry and Applications
- Glycosylation and Glycoproteins Research
- Peptidase Inhibition and Analysis
- Corneal surgery and disorders
- Drug Solubulity and Delivery Systems
- Nanoparticle-Based Drug Delivery
- biodegradable polymer synthesis and properties
- Advanced Polymer Synthesis and Characterization
- Ocular Disorders and Treatments
- Intraocular Surgery and Lenses
- Electrospun Nanofibers in Biomedical Applications
- Protein Structure and Dynamics
- Innovative Microfluidic and Catalytic Techniques Innovation
- Protease and Inhibitor Mechanisms
University College London
2015-2024
Moorfields Eye Hospital NHS Foundation Trust
2013-2023
National Institute for Health Research
2013-2023
The London College
2012-2022
Institute of Ophthalmology
2018
Transnational Press London
2015-2018
Moorfields Eye Hospital
2008-2017
Engineering and Physical Sciences Research Council
2016
University of London
2005-2015
University College Lahore
2012-2015
The covalent conjugation of a functionalized poly(ethylene glycol) (PEG) to multiple nucleophilic amine residues results in heterogeneous mixture PEG positional isomers. Their physicochemical, biological, and pharmaceutical properties vary with the site PEG. Yields are low because inefficient chemistry production costs high complex purification procedures. Our solution these fundamental problems PEGylating proteins has been exploit latent selectivity two sulfur atoms that derived from...
Terpolymerization of poly(ethylene glycol) (PEG), divinyl ethers, and serinol can be used to synthesize water soluble, hydrolytically labile, amino-pendent polyacetals (APEGs) suitable for drug conjugation. As these display pH-dependent degradation (with faster rates hydrolysis at acidic pH) they are not inherently hepatotropic after intravenous (iv) injection, have potential development as biodegradable carriers facilitate improved tumor targeting anticancer agents. The aim this study was a...
The water-soluble, biocompatible polymer poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) was evaluated for protein conjugation. PMPC is a zwitterionic that able to form more compact conformation in aqueous solution than poly(ethylene glycol) (PEG). While terminally functionalized N-hydroxysuccinimide derivative of not efficient conjugation an amine moiety on interferon-alpha2a (IFN), we found bis-thiol specific could be conjugated after reduction the disulfide bonds IFN. Utilizing...
The efficacy of protein-based medicines can be compromised by their rapid clearance from the blood circulatory system. Achieving optimal pharmacokinetics is a key requirement for successful development safe medicines. Protein PEGylation clinically proven strategy to increase circulation half-life One limitation that there are few strategies achieve site-specific conjugation PEG protein. Here, we describe covalent site-specifically polyhistidine tag (His-tag) on His-tag was achieved with...
Transdermal delivery of biological therapeutics is emerging as a potent alternative to intravenous or subcutaneous injections. The latter possess major challenges including patient discomfort, the necessity for trained personnel, specialized sharps disposal, and risk infection. microneedle (MN) technology circumvents many abovementioned challenges, delivering materials directly into skin allowing sustained release active ingredient both in animal models humans. This study describes use...
Dry eye disease is a common ocular disorder that characterised by tear deficiency or excessive evaporation. Current treatment involves the use of drops; however, therapeutic efficacy limited because poor bioavailability topically applied formulations. In this study, digital light processing (DLP) 3D printing was employed to develop dexamethasone-loaded punctal plugs. Punctal plugs with different drug loadings were fabricated using polyethylene glycol diacrylate (PEGDA) and 400 (PEG 400)...
The synthetic polymers that are used to prepare polymer therapeutics reaching clinical use predominantly nonbiodegradable, and this severely limits the molecular weight range will give certainty of safe elimination. aim study was synthesize water-soluble, biocompatible, amino-functionalized polyacetals would display pH-dependent degradation and, moreover, be suitable for drug conjugation. To test feasibility procedure, were first prepared by reaction a diol (e.g., poly(ethylene glycol)...
Protein PEGylation is the most clinically validated method to improve efficacy of protein-based medicines. Antibody fragments such as Fabs display rapid clearance from blood circulation and therefore are good candidates for PEGylation. We have developed PEG-bis-sulfone reagents 1 that can selectively alkylate both sulfurs derived a native disulfide. Using 1, conjugation PEG specifically targets disulfide distal binding region Fab (Scheme 2 ). (10-40 kDa) were used generate corresponding...
Coating thickness estimates of coated gold nanoparticles was achieved to avoid reduction diagnostic sensitivity from excess antibody.
Site-selective conjugation generally requires both (i) molecular engineering of the protein interest to introduce a site at defined location and (ii) site-specific technology.