Mesoporous silica Nanoparticles have been extensively investigated as Smart Drug Delivery System for various Bio-medical applications including cancer treatment owing to its distinctive structure, Bio-compatibility and versatility. Although, extensive research findings are essential concerning toxicity studies to scale it further to Clinical Trials and for regulatory approvals.
Mesoporous Silica Nanoparticles (MSNs) have attracted great attention over the last decade as a drug delivery system in the fields of biotechnology and Nano medicine due to their unique and adjustable physiochemical properties. MSNs were first synthesised by Mobil researchers in 1992 and were called Mobil Crystalline Materials (MCM). Some years later, the research group of Terasaki performed an excellent characterisation that allowed to understand the behavior of these materials and to project them to new and important applications. The various researches are going on for chemical synthesis which can lead to the various fruitful applications of MSN in Nano medicine. From catalysis to medical and Nano technological applications, there are uncountable new materials from the discovery of mesoporous solids. MSNs have been explored for a wide variety of therapeutic agents to fight against various kinds of diseases including diabetes, cancer, inflammation and bone/tendon tissue engineering.
MSNs are solid materials, which contain hundreds of empty channels (mesopores) arranged in a 2D network of honeycomb-like porous structure and possess some exclusive advantages including high surface area (>700 m2/g) and large pore volume (>0.9 cm3/g), tunable particle size (10-1000 nm) and pore diameter (2-30 nm), tunable pore structures and physicochemical stability, uniform mesoporosity, flexible morphology, facile surface functionalisation, excellent biocompatibility and biodegradation. Due to their unique adjustable properties, MSNs can serve as versatile drug delivery carriers. They also present a stable and rigid framework with excellent chemical, thermal, and mechanical stability.
In the beginning MSNs were used for controlled delivery of various hydrophilic or hydrophobic active agents. Later advances in the MSNs surface properties such as surface functionalisation and PEGylation rendered them as a promising drug delivery vehicle for cancer treatment. The textural properties of MSNs provide the possibility to load high amount of drugs within MSNs carriers as there are abundant silanol groups on the surfaces of mesoporous channels and the outer surfaces of MSNs, it facilitate the surface functionalisation to allow for a better control over the drug diffusion kinetics. Furthermore, both the exterior particle and interior pore surfaces can also be easily functionalised for site-specific delivery. In addition, functional materials, such as magnetic nanoparticles, luminescent materials and polymers, can be combined with MSNs to form functional MSNs, which induce MSNs as multifunctional platforms to realise the targeted controlled drug delivery and/or imaging. Due to their potential application in various fields such as gate keeping, controlled drug delivery system, and bio sensing; many efforts have been focused on the modification of the pore size and structure of MSNs.
Among the various drug delivery systems based on inorganic materials, like gold nanoparticles, metal oxide such as iron oxide particles, carbon nanotubes, quantum dots; MSN with a core-shell structure can be utilised as multifunctional platforms for simultaneous targeted drug delivery, fast diagnosis, and efficient therapy. The magnetic-luminescent MSNs can serve as an all-in-one diagnostic and therapeutic tool, which could be used to visualise and simultaneously treat various diseases. Mesoporous silica cores also serve as “gatekeepers” to trigger drug release only upon exposure to stimuli, which could decrease side-effect to protect the healthy organs from toxic drugs and prevent the decomposition/ denaturing of the drugs before reaching the targeted organs or tissues. The functionalisation of MSNPs with molecular, supramolecular or polymer moieties, provides the material with great versatility while performing drug delivery tasks, which makes the delivery process highly controllable. This emerging area at the interface of chemistry and the life sciences offers a broad palette of opportunities for researchers with interests ranging from sol–gel science, the fabrication of nanomaterials, supramolecular chemistry, controllable drug delivery and targeted theranostics in biology and medicine.
The synthesis, characterisation, and application of novel porous materials have been strongly encouraged due to their wide range of applications in adsorption, separation, catalysis, and sensors but the design, synthesis, and modification of porous materials are in some aspects more challenging than the synthesis of dense materials. Therefore, new strategies and techniques are continuously being developed for the synthesis and structure-tailoring of Mesoporous materials. Nano-sized mesoporous silicas were first successfully synthesised and reported by the groups of Cai, Mann and Ostafin. Then the term MSN was popularised by Victor Lin to represent mesoporous silica nanospheres. The synthesis of MSNs is carried out either through the alkaline or the acidic route both using amphiphiles as templates. Since the discovery of mesoporous silicas synthesised using cationic surfactants as templates, the templating method has been widely applied. These methods can be designed to give various mesostructures, morphologies and dimensions by controlling the reaction conditions such as reaction temperature, pH value, surfactants concentration, silica sources etc. to suit the specific application. Taking advantage of rich silane chemistry, many multifunctional MSNs have been created and applied, and the MSN material is now one of the most widely studied nanomaterials in the field of nano-biomedicine. On the other hand, the developed synthesis methods to functional MSNs with a core-shell structure are limited to produce a small amount of nanoparticles. Therefore, the scaled synthesis routes to functional MSNs with a core-shell structure are very important for the final possible biomedical applications.
So far, no clinical trials were performed with MSN but an early phase I study (NCT02106598) is conducted with targeted silica nanoparticles for image-guided operative sentinel lymph node mapping. Silica is classified as “Generally Recognized as Safe” (GRAS) by the FDA and is used in cosmetics and as a food-additive.
The one research study reported that when MSNs of various sizes were administrated subcutaneously to mice, it appeared to be nontoxic and the amount of residual material decreased progressively over 3 months, with good biocompatibility on histology at all-time points while the same doses of MSNs administrated intra-peritoneal and intra-venous injections in mice resulted in death or euthanasia. In contrast, other studies demonstrated that fluorescent MSNs are biocompatible at effective dosages, able of reducing toxicity of anticancer drugs; accumulate in tumour xenografts with or without targeting moieties and exhibit excellent tumor suppressing effect. The effects of different exposure routes including intravenous, hypodermic, intramuscular injection and oral administration on the absorption, distribution, excretion and toxicity of SNs in vivo were systematically investigated by the researchers. The results demonstrated that SNs could be hardly absorbed in a short time after hypodermic and intramuscular administration. Pathological examinations illustrated that SNs possessed good tissue biocompatibility after oral and intravenous injection. These findings revealed that oral and intravenous administration were relatively safe routes for possible biomedical application.
Although the structure morphology, surface properties, and size of MSNs have been found to be tunable for the purpose of controlled drug delivery and multifunctional in drug delivery; there are major concerns about the biocompatibility, toxicity, in vivo bio-distribution and efficacy of MSNs of various particle sizes as the knowledge on the in-vivo biocompatibility, toxicity and in- vivo bio-distribution of MSNs is still very limited. Another drawback is the premature drug leakage from the silica pores resulting reduced delivery of the actives at the desired sites. Most importantly there is a lack of human clinical trials and the few existing studies in animal models cannot provide sufficient evidence on MSNs safety.
Thus, Mesoporous silica nanoparticles are a promising and smart drug delivery system for various diseases but still significant clinical studies are necessitated to further explore it to the large scale production and for regulatory approvals.
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