Search

Due to recent advances in science and technology, when the products used in therapy are examined, ophthalmology has a priority in terms of research and development, preclinical and clinical studies of innovative drugs, medical devices and drug-medical device combination products. Liposomes, micelles, nanoemulsions, nanoparticles with colloidal structures and intraocular implants as sustained-release drug delivery systems have been developed to overcome the barriers to ocular applications, increase absorption, decrease metabolism and elimination and increase the residence time in ocular tissues and compartments. Studies are also ongoing in the area of advanced therapies using gene or cell-based systems which are high-risk products due to their complex structures. In this review, ocular drug, gene and cellular delivery systems and related products and developments in advanced therapy medicinal products are presented in respect to the definition of drug (medicinal product) and current changes in legislation. [ABSTRACT FROM AUTHOR]

The widespread use of digital slides has only recently come to the fore with the development of high-throughput scanners and high-performance viewing software. Here, the use of this technology in the creation of a comprehensive library of images of preclinical toxicological relevance is demonstrated. The images, acquired using the Aperio ScanScope™ CS and XT digital slide acquisition systems, form part of the ongoing EU FP6 Integrated Project, InnoMed. In more detail, PredTox (Predictive Toxicology) is a subproject of InnoMed and comprises a consortium of 15 industrial (13 large pharma, 1 technology provider and 1 SME) and 3 academic partners. The primary aim of this consortium is to assess the value of combining data generated from ‘omics technologies (proteomics, transcriptomics, metabolomics) with the results from more conventional toxicology methods, to facilitate more informed decision making in preclinical safety evaluation. A library of 1900 scanned images was created of full-face sections of liver and kidney tissue specimens from male Wistar rats treated with 16 proprietary and reference compounds of known toxicity; additional biological materials from these treated animals were separately used to create ‘omic data, that will ultimately be used to populate an integrated toxicological database. In respect to assessment of the digital slides, a web-enabled digital slide management system, Digital Slide Server (DSS), was employed to enable integration of the digital slide content into the “omics” database and to facilitate remote viewing of digital slides by pathologists connected with the project. DSS also facilitated manual annotation of digital slides by the pathologists, specifically in relation to marking particular toxicological lesions of interest. Tissue microarrays (TMAs) were also constructed from these specimens for the purpose of creating a repository of tissue from animals used in the study with a view to later-stage biomarker assessment. As the PredTox consortium itself aims to identify new biomarkers of toxicity, these TMAs will be a valuable means of validation. In summary, a large repository of toxicological images was created enabling the subsequent pathological analysis of samples through remote viewing and, along with the utilisation of TMA technology, will allow the validation of biomarkers identified by the PredTox consortium. [Copyright &y& Elsevier]