Drug Loading Methods and Kinetic Release Models Using of Mesoporous Silica Nanoparticles as a Drug Delivery System: A Review
Abstract
Oral drug administration remains one of the most convenient routes due to its Simplicity, high patient compliance, and cost-effectiveness. However, many medicinal products available on the market exhibit poor water solubility, which adversely affects the dissolution rate of drugs in biological fluids. Drug loading is a promising strategy to produce highly stable amorphous drugs with improved dissolution rates, solubility, and bioavailability. Mesoporous silica nanoparticles (MSNs) are particularly advantageous due to their tunable surface area, pore size, and pore volume, making them suitable to load various molecules such as drugs, genes, and proteins. The use of mathematical models is crucial for predicting and analyzing the release profile of active molecules and diffusion patterns within delivery systems. This enables the design and development of new systems with more desirable release patterns. This review provides an overview of MSNs and drug loading methods, discusses the mechanisms of drug release and release kinetic models using mesoporous carriers, and highlights critical considerations in designing MSNs, such as particle stability and cytotoxicity.
Highlights
- The types, synthesis parameters and functionalization methods of MSNs are explored
- An overview of drug loading techniques using MSNs is discussed
- The release mechanism and kinetic release models related to mesoporous carriers are investigated
- The critical consideration for designing ideal carriers, such as particle stability and biocompatibility, are highlighted
Introduction
Drug delivery systems (DDS) aim to transport drugs from the initial administration site to the targeted site of infection or disease (Huang et al., 2021). Oral drug administration is still the most convenient route as it is easiest to take, has high patient compliance, and is cost-effective. Furthermore, some estimates suggest that oral formulations comprise 90% of manufacturing drugs and about 50% of the drug delivery market (Laracuente et al., 2020). Despite these advantages, oral drug delivery poses a significant challenge before it gets the therapeutic purpose. These difficulties are primarily induced by The biological barriers along the way of traveling drug molecules inside the body. These barriers include the degradation environment of acidic fluids in the stomach, enzymatic degradation, low absorption capacity, and the low permeability of active molecules through the intestinal wall (Ahadian et al., 2020). In addition, most medicinal products available in markets are poorly soluble water, which affects the dissolution rate of drugs inside the biological fluids (Sreeharsha et al., 2022).
As a result, oral bioavailability is much lower than other administration routes. The use of conventional drug delivery systems could be accompanied by adverse effects as higher doses of drugs are required to elevate the bioavailability. Furthermore, these systems usually exhibit unspecified bio-distribution and missing controllability of the drug release characteristics (Laffleur and Keckeis, 2020). Novel DDS should be able to protect the drug from the harsh environment, increase the absorption of the drug into the circular systems, and promote controlled release to specific target sites (Lou et al., 2023). Nanotechnology enables us to produce novel pharmaceuticals by precisely targeting diseased areas, minimizing the toxicity of active molecules, and lowering healthcare costs. A large number of nanocarriers with different properties have been synthesized and applied to drug delivery, such as liposomes (Fan et al., 2021), micelles (Movassaghian et al., 2015), polymers, quantum dots (Ye et al., 2014), metal oxide nanoparticles, metal-organic frameworks (MOFs) (Fard et al., 2024), Zeolites (Servatan et al., 2020) and mesoporous silica nanoparticles (Albayati et al., 2019; Ali et al., 2024). Inorganic nanoparticles gained significant attention in developing innovative drug delivery systems due to their large uptake capacity, high selectivity, good biocompatibility, and high stability compared to organic nanoparticles (Paul and Sharma, 2020). Amongst various inorganic nanomaterials, mesoporous silica nanoparticles (MSNs) have attracted attention due to their tunable surface area, pore size, and pore volume (Ali et al., 2023; Mahdi et al., 2023).
Their unique porous structure with low-density solids, high silanol groups, tunable surface activity, and controllable selectivity makes them a popular choice in different science sectors (Fig. 1) (Djayanti et al., 2023; Tella et al., 2022). Due to MSNs tunable characteristics, it is easy to load different kinds of molecules such as drugs, genes, and proteins. Besides that, it can be modified easily with functional groups to increase the loading capacity and enhance the release rate (Kazemzadeh et al., 2022). MSNs offer many outstanding advantages over other inorganic materials, for instance, good biocompatibility, biodegradability, and high chemical, thermal, mechanical, and biological stability (Hoang Thi et al., 2019). Subsequently, MSNs have emerged as a good candidate in biomedical and drug delivery applications in recent years. Several literature reviews have investigated the effectiveness of drug loading methods by MSNs to produce stable amorphous drugs with enhanced solubility and bioavailability (Khalbas et al., 2024; Seljak et al., 2020; Trzeciak et al., 2021) . Furthermore, Previous literature extensively investigated the release kinetic models, with a primary focus on organic matrices such as polymers (Jahromi et al., 2020; Fu and Kao, 2010) .
Therefore, the purpose of this review is to expand the knowledge of previously published work by providing new insight into drug loading techniques related to MSNs, with a particular emphasis on the principles of kinetic release models using inorganic matrices. This review explores the different types of MSNs, investigates the principles and control parameters for synthesizing mesoporous silica, and comprehensively examines various techniques for drug encapsulation into MSNs. It also discusses and examines mass transfer mechanisms in controlled release systems involving both porous and non-porous materials. Additionally, the application of release kinetic models for drug-loaded mesoporous silica carriers is discussed. Finally, Key considerations for designing ideal MSNs, such as particle stability and cytotoxicity, are also highlighted.
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Table 3. Some studies related to drug loading methods using mesoporous silica nanoparticles.
| Loading method | MSN type | Active drug | Loading (wt.%) | Re |
|---|---|---|---|---|
| Incipient wetness impregnation | MCM-41 Mg-MCM-41 | Kaempferol | ||
| Incipient wetness impregnation | SBA-15 | Mirtazapine | ||
| Solvent evaporation | SBA-15 Zn- SBA-15 | Quercetin | ||
| Solvent evaporation | SBA-15 | Carbamazepine | 20 | |
| Adsorption Equilibrium | MSNs | Carvedilol | ||
| Adsorption Equilibrium | MCM-41 SBA-15 | Mirtazapine | ||
| One pot drug loading and synthesis | MSNs | Doxorubicin | ||
| One pot drug loading and synthesis | SBA-15 | Ibuprofen Heparin | ||
| Supercritical carbon dioxide method | MCM-41 | Ibuprofen | ||
| Liquid carbon dioxide (CO2) method | NH2-MCM-41 PO3-MCM-41 | Meropenem | ||
| Co-spray drying | SBA-15 | Artemisinin | ||
| Co-spray drying | MSNs | Fenofibrate | ||
| Fluidized bed dryer | MSNs | Paracetamol | ||
| Melt method | SBA-15 | Indomethacin Iitraconazole | ||
| Fluid bed hot-melt impregnation | MSNs | Ibuprofen | ||
| Microwave-assisted loading | SBA-15 Syloid® | Fenofibrate | ||
| Microwave-assisted loading | Syloid AL-1 Syloid 244 Syloid 72 | Gemfibrozil | ||
| Milling-assisted loading | SBA-15 | Ibuprofen | ||
| Milling-assisted loading | Syloid®XDP3050 | Mangiferin |
Ali H. Khalbas, Talib M. Albayati, Nisreen S. Ali, Issam K. Salih, Drug Loading Methods and Kinetic Release Models Using of Mesoporous Silica Nanoparticles as a Drug Delivery System: A Review, South African Journal of Chemical Engineering, 2024, ISSN 1026-9185, https://doi.org/10.1016/j.sajce.2024.08.013.
Read also our introduction article on Mesoporous Silica here:
