Molecular therapy in ocular wound healing (original) (raw)
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Borneo Journal of Pharmacy, 2022
The eye is an organ that allows us to observe the outside world. Pathologies of the eye's posterior segment, such as glaucoma, macular degeneration, diabetic retinopathy, uveitis, and retinoblastoma, cause vision loss. Traditional treatments consist of applying topical medications that do not penetrate properly or using high doses that generate adverse effects. Different laser surgeries stop the pathology's progression but do not allow visual improvement. So, an alternative is to use monoclonal antibodies, proteins produced by different processes that selectively bind to metabolites associated with diseases, reducing the adverse effects of traditional treatments and improving the application of the drug in the area. The two main molecular targets are TNF (adalimumab, infliximab, and certolizumab pegol) and VEGF (bevacizumab and ranibizumab); other possibilities are under investigation.
Therapeutic antibodies for improved wound healing
Therapeutic monoclonal antibodies (mAbs) are the fastest growing area of drug development, with an increasing number of diseases, including rheumatoid arthritis, multiple sclerosis and various forms of cancer, now amenable to treatment. Therapeutic mAbs bind to proteins or cells that are involved in the development of disease, impairing their ability to further contribute to the pathology. Currently, the treatment of acute and chronic wounds is an area of unmet clinical need. There are a number of proteins and cell types that are detrimental to wound healing and are up-regulated in the wound environment, especially in chronic wounds, with a reduction expected to improve healing outcomes. Therapeutic mAbs may therefore potentially provide a valuable new tool for wound treatment. This review explores the application of mAb therapies in wound healing.
Monoclonal antibodies - a proven and rapidly expanding therapeutic modality for human diseases
2010
The study of antibodies has been a focal point in modern biology and medicine since the early 1900s. However, progress in therapeutic antibody development was slow and intermittent until recently. The first antibody therapy, murine-derived murononab OKT3 for acute organ rejection, was approved by the US Food and Drug Administration (FDA) in 1986, more than a decade after César Milstein and Georges Köhler developed methods for the isolation of mouse monoclonal antibodies from hybridoma cells in 1975. As a result of the scientific, technological, and clinical breakthroughs in the 1980s and 1990s, the pace of therapeutic antibody discovery and development accelerated. Antibodies are becoming a major drug modality with more than two dozen therapeutic antibodies in the clinic and hundreds more in development. Despite the progress, need for improvement exists at every level. Antibody therapeutics provides fertile ground for protein scientists to fulfill the dream of personalized medicine through basic scientific discovery and technological innovation. KEYWORDS monoclonal antibodies, personalized medicine, therapeutic antibodies
Wound Repair and Regeneration, 2004
Biocompatible matrices, such as bovine collagen, have demonstrated usefulness in delivering gene therapy vectors that express growth factors to local environments for tissue repair. Unlike animal derived matrices, we have developed a new synthetic matrix consisting of a linear cyclodextrin-polyethyleneglycol co-polymer that is non-covalently cross-linked with di-adamantane-polyethyleneglycol via inclusion complex formation between adamantane and cyclodextrin (CD-Ada). We performed both in vitro and in vivo experiments for biocompatibility and localized transgene expression using a recombinant adenovirus (rAd) vector containing either the reporter gene, GFP, or the therapeutic gene, PDGF-B. In vitro results demonstrated cell migration, adenoviral transduction, and gene expression with no visible signs of toxicity in human skin fibroblasts. Qualitative gene expression from the CD-Ada containing rAd was delayed by approximately two days when compared to collagen, but the level of expression was greater over a longer period of time. In vivo experiments demonstrated gene expression after local delivery to mouse skin using rAd-GFP in CD-Ada. Again, the expression was slightly delayed but duration of expression was comparable to collagen. Expression studies using rAd-PDGF-B, were performed in the rat polyvinyl alcohol sponge model and showed comparable quantitative DNA and RNA levels between CD-Ada and collagen (DNA: 4.1 • 10 10 and 4.5 • 10 10 MEQ of PDGF-B/assayed sponge, respectively; RNA: 7.0 • 10 8 and 3.2 • 10 8 MEQ of PDGF-B/assayed sponge, respectively). Additionally, we explored the use of plasmid DNA with the CD-Ada matrix and observed PDGF-B expression in vivo. Our results show that this new delivery system provides a safe, efficient, and adaptable medium for both viral and non-viral gene delivery.