Research in designing and engineering long-circulating nanoparticles, so-called 'stealth' nanoparticles, has been attracting increasing interest as a new platform for targeted drug delivery, especially in chemotherapy. In particular, the modification of nanoparticulate surfaces with poly(ethylene glycol) derivatives has illustrated a decreased uptake of nanoparticles by mononuclear phagocyte system cells and, hence, an increased circulation time, allowing passive accumulation in the tumor. The clinical trials on patients with solid tumors are described in this article, to illustrate this generation of promising nanoparticles. In the last few years, the new-generation technique of grafting ligands on the nanoparticle surface in order to target and penetrate specific cancer cells has been developed. This article discusses the benefits of passive targeting for drug delivery to the solid tumors via the enhanced permeability and retention effect, when using stealth nanoparticles, and compares them with the advantages of active targeting.
Ferrociphenol (Fc-diOH) is a new molecule belonging to the fast-growing family of organometallic anti-cancer drugs. In a previous study, we showed promising in vivo results obtained after the intratumoural subcutaneous administration of the new drug-carrier system Fc-diOH-LNCs on a 9L-glioma model. To further increase the dose of this lipophilic entity, we have created a series of prodrugs of Fc-diOH. The phenol groups were protected by either an acetyl (Fc-diAc) or by the long fatty-acid chain of a palmitate (Fc-diPal). LNCs loaded with Fc-diOH prodrugs have to be activated in situ by enzymatic hydrolysis. We show here that the protection of diphenol groups with palmitoyl results in the loss of Fc-diOH in vitro activity, probably due to a lack of in situ hydrolysis. On the contrary, protection with an acetate group does not affect the strong, in vitro, antiproliferative effect of ferrocifen-loaded-LNCs neither the reduction of tumour volume observed on an ectopic model, confirming that acetate is easily cleaved by cell hydrolases. Moreover, the cytostatic activity of Fc-diOH-LNCs is confirmed on an orthotopic glioma model since the difference in survival time between the infusion of 0.36 mg/rat Fc-diOH-LNCs and blank LNCs is statistically significant. By using LNCs or Labrafac to carry the drug, a dose-effect ranging from 0.005 to 2.5mg of Fc-diOH per animal can be evidenced.
These results demonstrate the interesting perspectives for the systemic treatment of glioma thanks to bio-organometallic chemotherapy via lipid nanocapsules.
To utilize the potent pharmaceutical properties of curcumin (Cur) and gelatin-based materials in tissue regeneration, we fabricated a thermosensitive nanocomposite hydrogel based on pluronic-grafted gelatin (PG) and nanocurcumin (nCur) to enhance burn healing. In this method, the amphiphilic PG played a role as a surfactant to prepare and protect nanosized Cur particles, which could overcome the poor dissolution of the phytochemical. The synthesized PG was identified by 1 H nuclear magnetic resonance. Depending on the amount of Cur, size distribution of the dispersed nCur ranged from 1.5 ± 0.5 to 16 ± 3.2 nm as observed using transmission electron microscopy and dynamic light scattering. The nCur-dispersed PG solution formed nCur-PG nanocomposite hydrogel on warming up to 35 • C. Release profile indicated sustainable release of Cur from the injectable platform. Fibroblast cells were well proliferated on the nanocomposite hydrogel. The nCur-PG enhanced the healing process of second-degree burn wound. These results showed potential applications of the biomaterial in tissue regeneration.
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