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. 2021 Jul 26;22(15):7968.
doi: 10.3390/ijms22157968.

Kidney-Protector Lipidic Cilastatin Derivatives as Structure-Directing Agents for the Synthesis of Mesoporous Silica Nanoparticles for Drug Delivery

Samuel Martinez-Erro  1 , Francisco Navas  1 , Eva Romaní-Cubells  1 , Paloma Fernández-García  1 , Victoria Morales  1 , Raul Sanz  1 , Rafael A García-Muñoz  1
Affiliations

Kidney-Protector Lipidic Cilastatin Derivatives as Structure-Directing Agents for the Synthesis of Mesoporous Silica Nanoparticles for Drug Delivery

Samuel Martinez-Erro et al. Int J Mol Sci. .

Abstract

Mesoporous silica nanomaterials have emerged as promising vehicles in controlled drug delivery systems due to their ability to selectively transport, protect, and release pharmaceuticals in a controlled and sustained manner. One drawback of these drug delivery systems is their preparation procedure that usually requires several steps including the removal of the structure-directing agent (surfactant) and the later loading of the drug into the porous structure. Herein, we describe the preparation of mesoporous silica nanoparticles, as drug delivery systems from structure-directing agents based on the kidney-protector drug cilastatin in a simple, fast, and one-step process. The concept of drug-structure-directing agent (DSDA) allows the use of lipidic derivatives of cilastatin to direct the successful formation of mesoporous silica nanoparticles (MSNs). The inherent pharmacological activity of the surfactant DSDA cilastatin-based template permits that the MSNs can be directly employed as drug delivery nanocarriers, without the need of extra steps. MSNs thus synthesized have shown good sphericity and remarkable textural properties. The size of the nanoparticles can be adjusted by simply selecting the stirring speed, time, and aging temperature during the synthesis procedure. Moreover, the release experiments performed on these materials afforded a slow and sustained drug release over several days, which illustrates the MSNs potential utility as drug delivery system for the cilastatin cargo kidney protector. While most nanotechnology strategies focused on combating the different illnesses this methodology emphasizes on reducing the kidney toxicity associated to cancer chemotherapy.

Keywords: cilastatin; drug delivery systems; drug-structure-directing agent (DSDA); mesoporous silica nanoparticles (MSNs); sustained and controlled release.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(a) Cilastatin and (b) drug-structure-directing agents from cilastatin.
Figure 2
Figure 2
TEM images of the materials synthesized according to the reaction conditions in Table 1. (A) Cilastatin-C18@MSN-1; (B) Cilastatin-C18@MSN-2; (C) Cilastatin-C18@MSN-3; (D) Cilastatin-C18@MSN-4; (E) Cilastatin-C10@MSN-5; (F) Cilastatin-C10@MSN-6; (G) Cilastatin-C10@MSN-7; (H) Cilastatin-C10@MSN-8.
Figure 3
Figure 3
N2 adsorption–desorption isotherms and pore size distributions (PSD) based on a NLDFT model of Cilastatin-C18@MSN-3, Cilastatin-C18@MSN-4, Cilastatin-C18@MSN-5, and Cilastatin-C18@MSN-6.
Figure 4
Figure 4
N2 adsorption–desorption isotherms and pore size distributions (PSD) based on a NLDFT model of Cilastatin-C18@MSN-7 and Cilastatin-C10@MSN-8.
Figure 5
Figure 5
Release experiments of Cilastatin-C18@MSN-3 (red) and Cilastatin-C10@MSN-8 (blue).
See this image and copyright information in PMC

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