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Eur J Pharm Sci ; 97: 218-226, 2017 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-27916693


Pyridoclax is an original oligopyridine lead, very promising in treatment of chemoresistant cancers. However, from solubility measurement and permeability evaluation, it appeared that this compound can be considered as a BCS II drug, with a poor water solubility. To overcome this unfavorable property, two strategies were proposed and compared: pyridoclax di-hydrochloride salt synthesis and formulation of pyridoclax-loaded nanoemulsions (PNEs) efficiently performed by transposing the spontaneous emulsification process previously developed by our team. Whereas the salt improved the thermodynamic solubility of the drug by a factor 4, the apparent solubility of the encapsulated pyridoclax was 1000-fold higher. Their stability was assessed upon dilution in various complex biomimetic media relevant for oral administration (SGF, FaSSIF-V2, FeSSIF-V2) or for the intravenous route (PBS). The solubility of the salt was affected by the nature of the medium, indicating that it could precipitate after administration, negatively impacting its bioavailability and its efficiency in vivo. On the contrary, in all media, PNEs remained stable in terms of granulometric properties (determined by DLS), ζ-potential and encapsulation efficiency (measured by HPLC). Thus, such nanomedicines appear as a valuable option to perform preclinical studies on the promising pyridoclax.

Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Piridinas/síntese química , Cloreto de Sódio/síntese química , Composição de Medicamentos , Emulsões , Nanopartículas/administração & dosagem , Piridinas/administração & dosagem , Cloreto de Sódio/administração & dosagem , Solubilidade
Nanomedicine (Lond) ; 10(4): 589-601, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25723092


AIM & METHODS: The aim of the present work was to encapsulate paclitaxel (Ptx) in various lipid nanocapsules (LNCs) formulations and then to compare their pharmacokinetics and efficacy on a subcutaneous isograft model in rats. RESULTS: Three different Ptx formulations were obtained. Drug payloads ranged from 1.32 to 3.62 mg Ptx/g of formulation. After oral administration the area under concentration-time curve was higher (p < 0.05) if Ptx was encapsulated, (1,2 Distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(PEG)] (DSPE-PEG-NH2)) LNCs displaying the highest area under concentration-time curve (p < 0.05). Efficacy was better than control for standard LNCs after oral administration (p < 0.05) and for (DSPE-PEG-NH2) LNCs after intravenous administration. Despite good absorption, (DSPE-PEG-NH2) LNCs failed to remain efficient after oral route. CONCLUSION: This study highlights the importance of efficacy studies paired to pharmacokinetic studies for nanomedicines.

Antineoplásicos Fitogênicos/administração & dosagem , Glioma/tratamento farmacológico , Nanocápsulas/química , Paclitaxel/administração & dosagem , Fosfatidiletanolaminas/química , Polietilenoglicóis/química , Administração Oral , Aminação , Animais , Antineoplásicos Fitogênicos/farmacocinética , Antineoplásicos Fitogênicos/uso terapêutico , Linhagem Celular , Feminino , Glioma/patologia , Humanos , Injeções Intravenosas , Paclitaxel/farmacocinética , Paclitaxel/uso terapêutico , Ratos , Ratos Endogâmicos F344