title: Optimization of prednisolone-loaded long-circulating liposomes via application of Quality by Design (QbD) approach.
abstract: Quality by design principles (QbD) were used to assist the formulation of prednisolone-loaded long-circulating liposomes (LCL-PLP) in order to gain a more comprehensive understanding of the preparation process. This approach enables us to improve the final product quality in terms of liposomal drug concentration, encapsulation efficiency and size, and to minimize preparation variability. A 19-run D-optimal experimental design was used to study the impact of the highest risk factors on PLP liposomal concentration (Y1- μg/ml), encapsulation efficiency (Y2-%) and size (Y3-nm). Out of six investigated factors, four of them were identified as critical parameters affecting the studied responses. PLP molar concentration and the molar ratio of DPPC to MPEG-2000-DSPE had a positive impact on both Y1and Y2, while the rotation speed at the formation of the lipid film had a negative impact. Y3was highly influenced by prednisolone molar concentration and extrusion temperature. The accuracy and robustness of the model was further on confirmed. The developed model was used to optimize the formulation of LCL-PLP for efficient accumulation of the drug to tumor tissue. The cytotoxicity of the optimized LCL-PLP on C26 murine colon carcinoma cells was assessed. LCL-PLP exerted significant anti-angiogenic and anti-inflammatory effects on M2 macrophages, affecting indirectly the C26 colon carcinoma cell proliferation and development.
authors: a Department of Pharmaceutical Technology and Biopharmaceutics , Faculty of Pharmacy, University of Medicine and Pharmacy "Iuliu Haţieganu" , Cluj-Napoca , Romania.
authors: Bianca
authors: B
authors: Sylvester
authors: a Department of Pharmaceutical Technology and Biopharmaceutics , Faculty of Pharmacy, University of Medicine and Pharmacy "Iuliu Haţieganu" , Cluj-Napoca , Romania.
authors: Alina
authors: A
authors: Porfire
authors: a Department of Pharmaceutical Technology and Biopharmaceutics , Faculty of Pharmacy, University of Medicine and Pharmacy "Iuliu Haţieganu" , Cluj-Napoca , Romania.
authors: Dana-Maria
authors: DM
authors: Muntean
authors: a Department of Pharmaceutical Technology and Biopharmaceutics , Faculty of Pharmacy, University of Medicine and Pharmacy "Iuliu Haţieganu" , Cluj-Napoca , Romania.
authors: Laurian
authors: L
authors: Vlase
authors: b Department of Molecular Biology and Biotechnology , Faculty of Biology and Geology, Babes-Bolyai University , Cluj-Napoca , Romania , and.|c Molecular Biology Centre, Institute for Interdisciplinary Research in Bio-Nano-Sciences, Babes-Bolyai University , Cluj-Napoca , Romania.
authors: Lavinia
authors: L
authors: Lupuţ
authors: b Department of Molecular Biology and Biotechnology , Faculty of Biology and Geology, Babes-Bolyai University , Cluj-Napoca , Romania , and.|c Molecular Biology Centre, Institute for Interdisciplinary Research in Bio-Nano-Sciences, Babes-Bolyai University , Cluj-Napoca , Romania.
authors: Emilia
authors: E
authors: Licarete
authors: b Department of Molecular Biology and Biotechnology , Faculty of Biology and Geology, Babes-Bolyai University , Cluj-Napoca , Romania , and.|c Molecular Biology Centre, Institute for Interdisciplinary Research in Bio-Nano-Sciences, Babes-Bolyai University , Cluj-Napoca , Romania.
authors: Alina
authors: A
authors: Sesarman
authors: b Department of Molecular Biology and Biotechnology , Faculty of Biology and Geology, Babes-Bolyai University , Cluj-Napoca , Romania , and.|c Molecular Biology Centre, Institute for Interdisciplinary Research in Bio-Nano-Sciences, Babes-Bolyai University , Cluj-Napoca , Romania.
authors: Marius Costel
authors: MC
authors: Alupei
authors: b Department of Molecular Biology and Biotechnology , Faculty of Biology and Geology, Babes-Bolyai University , Cluj-Napoca , Romania , and.|c Molecular Biology Centre, Institute for Interdisciplinary Research in Bio-Nano-Sciences, Babes-Bolyai University , Cluj-Napoca , Romania.
authors: Manuela
authors: M
authors: Banciu
authors: a Department of Pharmaceutical Technology and Biopharmaceutics , Faculty of Pharmacy, University of Medicine and Pharmacy "Iuliu Haţieganu" , Cluj-Napoca , Romania.
authors: Marcela
authors: M
authors: Achim
authors: a Department of Pharmaceutical Technology and Biopharmaceutics , Faculty of Pharmacy, University of Medicine and Pharmacy "Iuliu Haţieganu" , Cluj-Napoca , Romania.
authors: Ioan
authors: I
authors: Tomuţă
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival; D003692:Delayed-Action Preparations; D065546:Drug Liberation; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry*; D051379:Mice; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011239:Prednisolone / Q000737:chemistry* / Q000494:pharmacology; D013499:Surface Properties
chemical_list: D020533:Angiogenesis Inhibitors; D000893:Anti-Inflammatory Agents; D003692:Delayed-Action Preparations; D008055:Lipids; D008081:Liposomes; D011092:Polyethylene Glycols; D011239:Prednisolone
keywords: Design space; PEGylated liposomes; QbD; drug targeting; prednisolone