RESUMO
The ocular delivery route presents a number of challenges in terms of drug administration and bioavailability. The low bioavailability following topical ophthalmic administration shows that there is a clear need for in-depth research aimed at finding both more efficacious molecules and formulations precisely targeted at the site of action. Continuous technological development will eventually result in improved bioavailability, lower dosages, reduced toxicity, fewer adverse effects, and thus better patient compliance and treatment efficacy. Technological development, as well as increasingly stringent quality requirements, help stimulate analytical progress. This is also clearly evident in the case of medicinal products used in the treatment of glaucoma, which are the subject of this review. Impurity profiling of PGF2α analogues, either in the pure substance or in the finished formulation, is a crucial step in assessing their quality. The development of specific, accurate and precise stability-indicating analytical methods for determining the content and related substances seems to be an important issue in relation to this tasks. A total of 27 official and in-house analytical methods are presented that are used for the analysis of latanoprost, travoprost and bimatoprost. The conditions for chromatographic separation with UV or MS/MS detection and the available results obtained during method validation are described. In addition, several aspects are discussed, with particular emphasis on the instability of the analogues in aqueous solution and the phenomenon of isomerism, which affects a potentially large number of degradation products.
Assuntos
Glaucoma , Prostaglandinas F Sintéticas , Humanos , Prostaglandinas F Sintéticas/efeitos adversos , Prostaglandinas Sintéticas/efeitos adversos , Cloprostenol/uso terapêutico , Espectrometria de Massas em Tandem , Composição de Medicamentos , Anti-Hipertensivos/uso terapêutico , Amidas , Glaucoma/tratamento farmacológicoRESUMO
Erythrocytes (RBCs) represent the main cell component in circulation and recently have become a topic of intensive scientific interest. The relevance of erythrocytes as a model for cytotoxicity screening of xenobiotics is under the spotlight of this review. Erythrocytes constitute a fundamental cellular model to study potential interactions with blood components of manifold novel polymer or biomaterials. Morphological changes, subsequent disruption of RBC membrane integrity, and hemolysis could be used to determine the cytotoxicity of various compounds. Erythrocytes undergo a programmed death (eryptosis) which could serve as a good model for evaluating certain mechanisms which correspond to apoptosis taking place in nucleated cells. Importantly, erythrocytes can be successfully used as a valuable cellular model in examination of oxidative stress generated by certain diseases or multiple xenobiotics since red cells are subjected to permanent oxidative stress. Additionally, the antioxidant capacity of erythrocytes, and the activity of anti-oxidative enzymes could reflect reactive oxygen species (ROS) generating properties of various substances and allow to determine their effects on tissues. The last part of this review presents the latest findings on the possible application of RBCs as drug delivery systems (DDS). In conclusion, all these findings make erythrocytes highly valuable cells for in vitro biocompatibility assessment, cytotoxicity screening of a wide variety of substances as well as drug delivery.