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

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.

L-arginine-containing mesoporous silica nanoparticles embedded in dental adhesive (Arg@MSN@DAdh) for targeting cariogenic bacteria

“…A lipidic derivative of L-arginine, N-oleoyl-L-arginine, was first synthesized to act as Drug-Structure-Directing Agent DSDA, i.e., a template with pharmacological activity to drive the formation of MSNs, a concept previously introduced by us [ 34 , 48 , 49 ]. For this purpose, DSDA must have an amphipathic character, hydrophilic headgroup and hydrophobic tail to address the formation of micelles in water.…”

L-Arginine-containing mesoporous silica nanoparticles embedded in dental adhesive for targeting cariogenic dental biofilm

“…The pore size distribution showed a maximum in a range between 2.2 and 5.1 nm, which revealed a morphology of mesoporous materials. The large hysteresis loop and wide pore size distribution suggest the adsorption of N 2 molecules in the intraparticle voids that corresponds with the internal hollow of these particles [34,48,49]. The low-angle X-ray diffraction pattern of the calcined material showed a XRD peak at 1.6 (2θ), which suggests an ordered distribution of the pores in the nanostructure of the MSNs (Fig.…”

“…A lipidic derivative of L-arginine, N-oleoyl-L-arginine, was rst synthesized to act as Drug-Structure-Directing Agent DSDA, i.e., a template with pharmacological activity to drive the formation of MSNs, concept previously introduced by us [34,48,49]. For this purpose, the DSDA must have an amphipathic character, hydrophilic headgroup and hydrophobic tail, to address the formation of micelles in water.…”

Nanoarchitectured prototypes of mesoporous silica nanoparticles for innovative biomedical applications

“…The performance efficacy of the retained structure-directing micelles and their complexes is explored by monitoring the compatibility issues surfactants towards cancer therapy [ 76 ]. Similarly, the newly designed synthetic templates, i.e., drug-structure-directing complexes, have been employed to fabricate MSNs with exceptional functional and structural advantages [ 77 – 79 ]. Compared to traditional surfactants, these drug-complex templates exhibit higher stability and robustness, resulting in the MSNs with high surface area and pore volume.…”

“…Interestingly, the lamellar pillars were grown inside the hollow shells of MSNs. Further, the authors demonstrated the fabrication of MSNs to deliver the lipidic derivatives of cilastatin, a kidney protector [ 79 ]. Similarly, Stewart et al explored the encapsulation of surfactant-like drugs (for instance, octenidine dihydrochloride) to fabricate the drugs structure-directing agents’ concept for antimicrobial therapy [ 77 ].…”