Problems associated with impaired gastrointestinal function are common in children with cerebral palsy. Typical gastrointestinal manifestations of cerebral palsy include dysphagia, gastroesophageal reflux disease and constipation, which in chronic course lead to the development of nutritional status disorders, micronutrient insufficiency, osteopenia, reduced immunity and rehabilitation potential. Often it is the gastroenterological aspects of management of children with cerebral palsy that determine the quality of life of the child and his family.
Introduction. The use of polymeric biodegradable nanoparticles (NP) as drug delivery systems is a promising approach to overcome histohematomatic barriers. Thus, poloxamer 188-coated poly (lactide-co-glycolide) (PLGA) NP are able to overcome blood-brain barrier and to deliver therapeutic agents, in particular doxorubicin, into intracranial tumour upon intravenous administration. It is important to evaluate NP interaction with blood components in preclinical studies.The objective of the study was to investigate cytotoxicity and hemocompatibility of doxorubicin-loaded PLGA NP (Dox-PLGA NP), to essess NP uptake by glioblastoma cells.Materials and methods. The influence of NP on coagulation cascade was evaluated by prothrombin time measuring before and after plasma incubation with NP. To assess NP thrombogenicity the platelet activation level was determined by flow cytometry. The NP hemolytic activity (released hemoglobin concentration) was measured spectrophotometrically. NP cytotoxicity was determined by MTS assay. NP uptake by human glioblastoma cells was evaluated by flow cytometry.Results. Dox-PLGA NP did not influence blood coagulation time and thrombocyte activity at concentrations up to 100 mcg/mL: PT values were 12–15 s for all tested samples, and P-selectin expression level did not exceed 15 %. All samples were not hemolytic after 3 h of incubation. Cytotoxicity of doxorubicin released from PLGA NP on glioma U87MG cells was comparable to that of free doxorubicin. As shown by flow cytometry Dox-PLGA NP were efficiently internalized into the cells.Conclusion. The study of hemocompatibility confirmed the safety of Dox-PLGA NP: NP did not influence blood coagulation system and did not induce hemolysis. NP were efficiently internalized into the human glioblastoma cells and produced considerable antitumor effect in vitro.
Профиль высвобождения активного ингредиента из наночастиц является одним из важнейших параметров наносомальной лекарственной формы. Разработаны и оптимизированы методы изучения кинетики высвобождения доксорубицина из наночастиц PLGA в модельные среды in vitro. Оптимальным методом отделения наночастиц является ультрацентрифугирование, а наиболее подходящей модельной средой — 1 % водный раствор полоксамера 188. Профиль высвобождения имеет выраженный двухфазный характер и подчиняется закону диффузии Фика. Изучение кинетики высвобождения доксорубицина в плазме крови ограничено низкой стабильностью в условиях эксперимента (4 ч при 37 °C).
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.