Pyrazolo[3,4-d]pyrimidines-loaded human serum albumin (HSA) nanoparticles: Preparation,characterization and cytotoxicity evaluation against neuroblastoma cell line |
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| Authors: | Anna Lucia Fallacara Arianna Mancini Claudio Zamperini Elena Dreassi Stefano Marianelli Mario Chiariello Gianni Pozzi Francesco Santoro Maurizio Botta Silvia Schenone |
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| Institution: | 1. Dipartimento Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Via A. Moro 2, I-53100 Siena, Italy;2. Dipartimento di Farmacia, Università di Pisa, Via Bonanno 6, 56126 Pisa, IT, Italy;3. Lead Discovery Siena S.r.l., Via Vittorio Alfieri 31, 53019, Castelnuovo Berardenga, Siena, Italy;4. Consiglio Nazionale delle Ricerche, Istituto di Fisiologia Clinica and Istituto Toscano Tumori, Core Research Laboratory, Via Fiorentina 1, 53100 Siena, Italy;5. Dipartimento di Biotecnologie Mediche, Università degli Studi di Siena, Laboratory of Molecular Microbiology and Biotechnology (L.A.M.M.B.), Policlinico Le Scotte, Viale Bracci, 16, V lotto, I piano, 53100 Siena, Italy;6. Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology Temple University, BioLife Science Building, Suite 333, 1900 North 12th Street, Philadelphia, PA 19122, United States;7. Dipartimento di Farmacia, Università degli Studi di Genova, Viale Benedetto XV, 3, 16132 Genova, Italy |
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| Abstract: | Pyrazolo3,4-d]pyrimidine derivatives 1–5, active as c-Src inhibitors, have been selected to be formulated as drug-loaded human serum albumin (HSA) nanoparticles, with the aim of improving their solubility and pharmacokinetic properties. The present study includes the optimization of a desolvation method-based procedure for preparing HSA nanoparticles. First, characterization by HPLC-MS and Dynamic Light Scattering (DLS) showed a good entrapment efficacy, a controllable particle size (between 100 and 200 nm) and an optimal stability over time, confirmed by an in vitro drug release assay. Then, 1–4 and the corresponding NPs were tested for their antiproliferative activity against neuroblastoma SH-SY5Y cell line. Notably, 3-NPs and 4-NPs were identified as the most promising formulation showing a profitable balance of stability, small size and a similar activity compared to the free drugs in cell-based assays. In addition, albumin formulations increase the solubility of pyrazolo3,4-d]pyrimidine avoiding the use of DMSO as solubilizing agent. |
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| Keywords: | Neuroblastoma c-Src Drug delivery Drug targeting Human serum albumin nanoparticles |
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