Amphiphilic polyaspartamide copolymer-based micelles for rivastigmine delivery to neuronal cells
| Autor: | Gaetano Giammona, Cinzia Scialabba, Giovanna Pitarresi, Flavio Rocco, Mariano Licciardi, Maurizio Ceruti |
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| Přispěvatelé: | Scialabba, C, Rocco, F, Licciardi, M, Pitarresi, G, Ceruti, M, Giammona G |
| Rok vydání: | 2012 |
| Předmět: |
Materials science
Phenylcarbamates Pharmaceutical Science Rivastigmine polyaspartamide micelles rivastigmine drug delivery neuronal cells Micelle Fluorescence spectroscopy Hydrophobic effect Mice Neuroblastoma chemistry.chemical_compound Drug Delivery Systems Cell Line Tumor Amphiphile Copolymer Animals Humans Organic chemistry Particle Size Micelles Alkyl Neurons chemistry.chemical_classification Polysorbate Drug Carriers General Medicine Hydrophobe Neuroprotective Agents Spectrometry Fluorescence chemistry Biophysics Peptides Hydrophobic and Hydrophilic Interactions |
| Zdroj: | Drug Delivery. 19:307-316 |
| ISSN: | 1521-0464 1071-7544 |
| DOI: | 10.3109/10717544.2012.714813 |
| Popis: | A novel polysorbate-80 (PS(80))-attached amphiphilic copolymer comprising a hydrophilic α,β-poly(N-2-hydroxyethyl)-D,L-aspartamide (PHEA) backbone and hydrophobic squalenyl-C(17) (Sq(17)) portions was synthesized and characterized; the formation of polymeric micelles was also evaluated. Rivastigmine free-base (Riv), a hydrophobic drug employed to treat Alzheimer's disease, was chosen as model drug to investigate micelle's ability to incorporate hydrophobic molecules and target them to neuronal cells. Micelle formation was studied through analyses including fluorescence spectroscopy and 2D (1)H-NMR NOESY experiments. Finally, the capacity of Riv-loaded micelles, versus free drug, to penetrate mouse neuroblastoma cells (Neuro2a) was evaluated. 2D (1)H-NMR NOESY experiments demonstrated that the PHEA-EDA-Sq(17)-PS(80) copolymer self-assembles into micelle structures in water, with a micelle core formed by hydrophobic interaction between Sq(17) alkyl chains. Fluorescence probe studies revealed the CAC of PHEA-EDA-Sq(17)-PS(80) micelles, which was 0.25 mg mL(-1). The micelles obtained had a nanometric hydrodynamic diameter with narrow size distribution and negative surface charge. The PHEA-EDA-Sq(17)-PS(80) micelles incorporated a large amount of Riv, and the system maintained the stability of Riv after incubation in human plasma. An in vitro biological assay evidenced no cytotoxic effects of either empty or loaded micelles on the neuronal cell lines tested. Moreover, the micelles are internalized by neuroblastoma cell lines with drug uptake depending on the micelles concentration. |
| Databáze: | OpenAIRE |
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