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Doxorubicin-loaded PLGA nanoparticles for the chemotherapy of glioblastoma: Towards the pharmaceutical development
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15.12.2019 |
Maksimenko O.
Malinovskaya J.
Shipulo E.
Osipova N.
Razzhivina V.
Arantseva D.
Yarovaya O.
Mostovaya U.
Khalansky A.
Fedoseeva V.
Alekseeva A.
Vanchugova L.
Gorshkova M.
Kovalenko E.
Balabanyan V.
Melnikov P.
Baklaushev V.
Chekhonin V.
Kreuter J.
Gelperina S.
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International Journal of Pharmaceutics |
10.1016/j.ijpharm.2019.118733 |
0 |
Ссылка
© 2019 Elsevier B.V. Brain delivery of drugs by nanoparticles is a promising strategy that could open up new possibilities for the chemotherapy of brain tumors. As demonstrated in previous studies, the loading of doxorubicin in poly(lactide-co-glycolide) nanoparticles coated with poloxamer 188 (Dox-PLGA) enabled the brain delivery of this cytostatic that normally cannot penetrate across the blood-brain barrier in free form. The Dox-PLGA nanoparticles produced a very considerable anti-tumor effect against the intracranial 101.8 glioblastoma in rats, thus representing a promising candidate for the chemotherapy of brain tumors that warrants clinical evaluation. The objective of the present study, therefore, was the optimization of the Dox-PLGA formulation and the development of a pilot scale manufacturing process. Optimization of the preparation procedure involved the alteration of the technological parameters such as replacement of the particle stabilizer PVA 30–70 kDa with a presumably safer low molecular mass PVA 9–10 kDa as well as the modification of the external emulsion medium and the homogenization conditions. The optimized procedure enabled an increase of the encapsulation efficiency from 66% to >90% and reduction of the nanoparticle size from 250 nm to 110 nm thus enabling the sterilization by membrane filtration. The pilot scale process was characterized by an excellent reproducibility with very low inter-batch variations. The in vitro hematotoxicity of the nanoparticles was negligible at therapeutically relevant concentrations. The anti-tumor efficacy of the optimized formulation and the ability of the nanoparticles to penetrate into the intracranial tumor and normal brain tissue were confirmed by in vivo experiments.
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Polyisobutylene-based thermoplastic elastomers for manufacturing polymeric heart valve leaflets: In vitro and in vivo results
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01.11.2019 |
Ovcharenko E.
Rezvova M.
Nikishau P.
Kostjuk S.
Glushkova T.
Antonova L.
Trebushat D.
Akentieva T.
Shishkova D.
Krivikina E.
Klyshnikov K.
Kudryavtseva Y.
Barbarash L.
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Applied Sciences (Switzerland) |
10.3390/app9224773 |
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Ссылка
© 2019 by the authors. Superior polymers represent a promising alternative to mechanical and biological materials commonly used for manufacturing artificial heart valves. The study is aimed at assessing poly(styrene-block-isobutylene-block-styrene) (SIBS) properties and comparing them with polytetrafluoroethylene (Gore-texTM, a reference sample). Surface topography of both materials was evaluated with scanning electron microscopy and atomic force microscopy. The mechanical properties were measured under uniaxial tension. The water contact angle was estimated to evaluate hydrophilicity/hydrophobicity of the study samples. Materials' hemocompatibility was evaluated using cell lines (Ea.hy 926), donor blood, and in vivo. SIBS possess a regular surface relief. It is hydrophobic and has lower strength as compared to Gore-texTM (3.51 MPa vs. 13.2/23.8 MPa). SIBS and Gore-texTM have similar hemocompatibility (hemolysis, adhesion, and platelet aggregation). The subcutaneous rat implantation reports that SIBS has a lower tendency towards calcification (0.39 mg/g) compared with Gore-texTM (1.29 mg/g). SIBS is a highly hemocompatible material with a promising potential for manufacturing heart valve leaflets, but its mechanical properties require further improvements. The possible options include the reinforcement with nanofillers and introductions of new chains in its structure.
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