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Abstract
In this paper, mesoporous silica nanoparticles (MSNs) were studied as vehicles for the delivery of the antitumoral drug gemcitabine (GEM) and of its 4-(N)-acyl derivatives, (4-(N)-valeroyl-(C5GEM), 4-(N)-lauroyl-(C12GEM) and 4-(N)-stearoyl-gemcitabine (C18GEM)). The loading of the GEM lipophilic prodrugs on MSNs was explored with the aim to obtain both a physical and a chemical protection of GEM from rapid plasmatic metabolization. For this purpose, MSNs as such or with grafted aminopropyl and carboxyethyl groups were prepared and characterized. Then, their different drug loading capacity in relation to the nature of the functional group was evaluated. In our experimental conditions, GEM was not loaded in any MSNs, while C12GEM was the most efficiently encapsulated and employed for further evaluation. The results showed that loading capacity increased with the presence of functional groups on the nanoparticles; similarly, the presence of functional groups on MSNs’ surface influenced the drug release profile. Finally, the cytotoxicity of the different preparations was evaluated and data showed that C12GEM loaded MSNs are less cytotoxic than the free drug with an activity that increased with the incubating time, indicating that all these systems are able to release the drug in a controlled manner. Altogether, the results demonstrate that these MSNs could be an interesting system for the delivery of anticancer drugs.
Highlights
Cancer is currently the second leading cause of death in the world after cardiovascular diseases [1], while it probably shows the highest clinical complexity
We have demonstrated a dependence of the loading ability of bare and functionalized mesoporous silica nanoparticles, MSNs, on molecular properties of the drug, in particular the steric hindrance
The drug molecules could be complexed into the pores of MSNs through van der Waals, hydrophobic forces and hydrogen bonds depending on size and lipophilic character
Summary
Cancer is currently the second leading cause of death in the world after cardiovascular diseases [1], while it probably shows the highest clinical complexity. The employed anticancer agents still present some drawbacks, limiting their efficacy: most cytotoxic drugs have low specificity, because they do not discriminate between cancerous and normal cells, leading to the onset of systemic toxicity and to adverse effects that limit treatment efficacy [2]. The emerging discipline of nanomedicine, that brings nanotechnology and medicine together in order to develop novel therapies and improve existing treatments, could provide an effective answer to the complexity of the cancer disease [3]. Nanomedicine offers additional therapeutic options compared to present conventional therapy and a large number of nanocarriers possessing the ability to carry and deliver therapeutic or diagnostic agents to the disease site are under development for applications related to cancer diagnosis and treatment [4,5,6,7].
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