Physico-chemical characterization of ferrocifen loaded lipid nanocapsules: different drug delivery systems depending on succinimido-ferrociphenol structure
Résumé
The resistance to the current chemotherapeutic drugs has obliged the scientific community to seek innovative strategies (molecules, nanoparticles or gel). In the late 1990s, Jaouen’s team synthesized a new class of bio-organometallic molecules called ferrocifens [1]. However, their high lipophilic nature requires a formulation stage before being administered in vivo. Lipid nanocapsules (LNCs), developed in 2001 [2], have shown their ability to successfully encapsulated ferrocifens. In last decades, ferrocifen loaded LNCs have demonstrated anticancer properties on multidrug-resistant cancers (glioblastoma, metastatic melanoma, breast cancer) on mice models [3]. The most recent family of ferrocifens (the succinimido-ferrociphenols) seems to be the most efficient on several resistant cancer cell lines, with IC50 in the nanomolar range [4]. As LNCs are composed of anoily core (caprylic/capric triglycerides), playing with the lipophilicity of the succinimido-ferrociphenols can be interesting to improve the drug loading in LNCs. In the present work, 50 nm LNCs loaded with six different succinimido-ferrociphenols were formulated. For each ferrocifen, the maximal drug loading was determined. Interestingly, the encapsulation of two ferroficens led to the formation of gels: it is unprecedent. In order to understand this phenomenon, tensiometry measurements were performed to determine a potential influence of the ferrocifen position in the LNCs.
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