Tailored surface silica nanoparticles for blood-brain barrier penetration: Preparation and in vivo investigation (2024)

FAQs

Can silica cross the blood brain barrier? ›

The promising results obtained by in vivo experiments, point out that silica nanoparticle derivatives are an efficient permeable delivery vehicle that are able to cross the BBB and reach the brain tissues via specific and non-specific mechanisms.

Silica is “Generally Recognized As Safe” by the United States Food and Drug Administration (FDA). Recently, silica nanoparticles in the form of Cornell dots (C dots) received FDA approval for stage I human clinical trial for targeted molecular imaging3, 4.

Their absorptive properties make them useful in papermaking as a drainage aid. They can serve as a binding agent in the manufacture of rubber, plastics, and concrete. Most notably, they are stable and non-toxic materials with innumerable applications in biomedicine.

2.2 Functionalized silica nanoparticles. In order to improve or modify the chemical and physical properties, silica NPs can be chemically functionalized via physical adsorption or covalent conjugation using silane chemistry with various target substances, such as polymers, ligands and some functional compounds.

Small polar molecules, such as glucose, amino acids, organic anions and cations, and nucleosides, can cross the blood-brain barrier by carrier-mediated transport.

Nanoparticles are small sized (1-100 nm) particles derived from transition metals, silver, copper, aluminum, silicon, carbon and metal oxides that can easily cross the blood-brain barrier (BBB) and/or produce damage to the barrier integrity by altering endothelial cell membrane permeability.

Approved by FDA and EFSA, silica is already used as excipient and food additive.

Approved Nanodrugs

Since 1995, 50 nanopharmaceuticals have received FDA approval and are currently available for clinical use. Nanodrugs are typically administered orally or intravenously, and less frequently transdermally.

Spherical and amorphous silica nanoparticles can be prepared by the hydrolysis reaction of TEOS in ethanol using water and ammonia using sol-gel method. The particle size of nano silica can be controlled by adding span 20, span 40 and span 60 surfactants.

The principal parameters of nanoparticles are their shape, size, surface characteristics and inner structure. Nanoparticles can be encountered as aerosols (solids or liquids in air), suspensions (solids in liquids) or as emulsions (liquids in liquids).

What does silica do to your brain? ›

Fights brain toxins: Research indicates that silica reduces aluminum build-up in the brain, which researchers have potentially linked to Alzheimer's disease. So the elderly and others at risk for this disease may benefit from silica supplementation, especially since silica levels in your body tend to decrease with age.

The administration of titanium oxide nanoparticles through any route leads to the absorption and translocation into the brain, which can affect brain development and function. Furthermore, they can cross the placental barrier and accumulate in the fetal brain, causing impairments in the fetal brain development [87].

However, there are various methods used for the preparation of polymeric nanoparticles such as desolvation, dialysis, ionic gelation, nanoprecipitation, solvent evaporation, salting out, spray drying and supercritical fluid.

The broad classification of nanoparticle synthesis is used of top-down and bottom-up techniques. The top-down technique involves physical participation approaches such as mechanical machining, physical vapor deposition (PVD), lithography, and pyrolysis through thermal evaporation pyrolysis [6].

Micro-emulsion synthesis method is widely used for the production of inorganic nanoparticles [24].

The blood-brain barrier is the barrier between the cerebral capillary blood and the interstitial fluid of the brain. It is made up of capillary endothelial cells and basem*nt membrane, neuroglial membrane, and glial podocytes, i.e., projections of astrocytes.

Symptoms include severe headache, confusion, and impaired judgment and memory. Coma, convulsions, and other brain problems can occur afterward [11]. Breakdown of the blood-brain barrier (BBB) during increased brain blood pressure leads to reduced blood flow and excess fluid in the brain [12].

Factors known to disrupt the BBB experimentally include arachidonic acid and the eicosanoids, bradykinin, histamine and free radicals. These active compounds, released in pathological tissue, may alter cytosolic calcium levels and induce second messenger systems leading to an alteration in BBB permeability.

Polymeric Nanoparticles. As nanoparticles possess suitable properties for drug delivery, such as controlled drug release and targeting efficiency, they have been widely used for the development of drug delivery carriers to cross the blood-brain barrier.

Different types of nanoparticles (NPs). Graphical representation of the most commonly used NPs for biomedical applications. NPs are typically by a size measuring not more than 100 nm and have significant potential for delivering drugs across the blood-brain barrier. The size of quantum dots is usually less than 10 nm.

What size can pass through blood-brain barrier? ›

Our experimental and calculated results suggested that the optimum size of nanoparticles for delivery into the brain via this mechanism would be 5 to 6 nm in our system.

As a material, colloidal silica has been used in tablet manufacturing as a glidant for decades and is generally recognized as safe by the US Food and Drug Administration (FDA). In addition, the commonly used food additive E551 is composed of 100 nm silica nanoparticles.

Silica dust particles become trapped in lung tissue causing inflammation and scarring. The particles also reduce the lungs' ability to take in oxygen. This condition is called silicosis. Silicosis results in permanent lung damage and is a progressive, debilitating, and sometimes fatal disease.

Silica nanoparticles are mesopores (2- to 50-nm pores) of silica that display unique physicochemical properties [17]. These nanocarriers can be prepared in a variety of sizes and shapes including nanohelices, nanotubes, nanozigzags, and nanoribbons.

The main limitations of MNPs are burst drug release and low stability features. To overcome this issue, surface ligands are attached to MNPs, which in turn improve the stability and solubility in biological environments along with exhibiting lesser side effects [72].

As we have seen, local delivery using nanoparticles occurs by basically two broad methods: direct placement (e.g. injection at the intended site of use), or a targeted/triggered approach after systemic administration. There are many ways in which these can and are being improved.

1.1 Types of nanomaterials

Nanomaterials can be categorized into four types [9, 10] such as: (1) inorganic-based nanomaterials; (2) carbon-based nanomaterials; (3) organic-based nanomaterials; and (4) composite-based nanomaterials.

Nanoparticles can be obtained from micellar solutions of anionic surfactants using as counter ion,the ion of the metal that is to be formed as nanoparticles. The most commonly used surfactant for the purpose is dodecyl sulfate and a wide variety of metal salts have been used as counter ion.

There are four main types of intentionally produced nanomaterials: carbon-based, metal-based, dendrimers, and nanocomposites. Carbon-based nanomaterials are intentionally produced fullerenes. These include carbon nanotubes and buckyballs.

What are 4 uses of nanoparticles? ›

Nanoparticles are now being used in the manufacture of scratchproof eyeglasses, crack- resistant paints, anti-graffiti coatings for walls, transparent sunscreens, stain-repellent fabrics, self-cleaning windows and ceramic coatings for solar cells.

The key advantages of nanoparticles are (1) improved bioavailability by enhancing aqueous solubility, (2) increasing resistance time in the body (increasing half life for clearance/increasing specificity for its cognate receptors and (3) targeting drug to specific location in the body (its site of action).

The first group ( Organic nanoparticles) includes - micelles, dendrimers, liposomes, hybrid, and compact polymeric NPs. The second group includes fullerenes, quantum dots, silica, and gold nanoparticles. Micelles are the nanoparticles composed of amphiphilic molecules, like polymers or lipids.

These data demonstrate that SiO₂-NPs possibly have a negative impact on the striatum and dopaminergic neurons as well as a potential risk for neurodegenerative diseases. There is potential concern with SiO₂-NPs' neurotoxicity in biomedical applications and occupational exposure in large-scale production.

Moreover, it has been shown that the performances to a cognitive test were positively correlated to the consumption of silica and that the risk of Alzheimer's disease (AD) was reduced in subjects who had the higher daily silica intake compared to the others.

Conclusion: This study confirmed that silica exposure is associated with an enhanced risk of mortality of hypertensive and pulmonary heart diseases.

In brief, NPs enhance the radiosensitivity of brain cells by promoting autophagy and hypoxia-induced oxidative stress, suggesting that this combination could be effective in treatment of brain diseases.

These nanoparticles are engineered to seek out tumor cells and destroy or used as an injectable, reversible male contraception. But, in the future, gold nanoparticles could even be used to control our brain — or rather, to activate brain cells remotely and help treat neurological disease.

Some nanoparticles, if they're based on certain metals, can interact with the hydrogen peroxide that is present in every cell, and convert it to a hydroxyl radical, which can enter the nucleus and then you potentially have DNA damage.

NMR Spectroscopy. NMR is a robust and nondestructive molecular characterization technique, which provides comprehensive structure information by analyzing the chemical environment of the nuclei. It has become one of the most versatile and effective techniques to characterize the structure of surface ligands.

What are two approaches practiced by material scientists to prepare nanoparticles? ›

11.1 Introduction. Nanoparticle synthesis can be performed by various methods such as physical, chemical, and biological approaches. Generally, the physical and chemical methods are considered the best to get uniform-sized nanoparticles with long-term stability.

Dynamic laser scattering (DLS), also known as photon correlation spectroscopy (PCS), is the most widely used method for analyzing particle size of nanoparticles. This method obtains particle size information by measuring the diffusion coefficient of nanoparticles in a liquid.

Hydrothermal synthesis is one of the most commonly used methods for preparation of nanomaterials. It is basically a solution reaction-based approach. In hydrothermal synthesis, the formation of nanomaterials can happen in a wide temperature range from room temperature to very high temperatures.

There are two general approaches for the synthesis of nanomaterials as shown in Figure 2: a) Top- down approach b) Bottom–up approach. Top-down approach involves the breaking down of the bulk material into nanosized structures or particles.

The nano-particles can be prepared by various processes divided into i.e. bottom up and top down techniques. Bottom up methods include the reduction of material components up to the atomic level and then with further self-assembly lead to the formation of nano-particles.

Effect of sodium hydroxide. The reaction was optimized for reaction time as well as the concentration of sodium hydroxide. Synthesized nanoparticles absorbance or optical intensity increased with increase in concentration of NaOH, as presented in figure 5.

Receptor-mediated transport allows glucose, ions, and other special molecules to cross the blood-brain barrier. Most large molecules and proteins are precluded from entering the barrier.

The transport of circulating nutrients (glucose, amino acids, ketone bodies, choline, and purines) through the brain endothelial wall, i.e., the blood-brain barrier (BBB), is an important regulatory step in several substrate-limited pathways of brain metabolism.

The blood–brain barrier restricts the passage of pathogens, the diffusion of solutes in the blood, and large or hydrophilic molecules into the cerebrospinal fluid, while allowing the diffusion of hydrophobic molecules (O₂, CO₂, hormones) and small non-polar molecules.

Silica dust particles become trapped in lung tissue causing inflammation and scarring. The particles also reduce the lungs' ability to take in oxygen. This condition is called silicosis. Silicosis results in permanent lung damage and is a progressive, debilitating, and sometimes fatal disease.

What happens if the blood-brain barrier is damaged? ›

A breakdown in the blood-brain barrier (BBB) is thought to be an early stage in this process. If the BBB is damaged or weakened in some way, immune cells are able to cross. These cells then attack the myelin around your nerves, which leads to nerve damage and MS symptoms.

Lipophilic dihydropyridine-based brain targeting of CDDS is a typical method for BBB penetration. Due to the lipophilicity of dihydropyridine, drugs connected with dihydropyridine could pass through the BBB. Once entering the brain parenchyma, the dihydropyridine is enzymatically oxidized into ionic pyridinium salt.

Circulating 25(OH) vitamin D crosses the blood-brain barrier and enters glial cells and neuronal cells to be converted into 1,25(OH) 2 D, which is the active form of vitamin D [11].

Research suggests that acute stress damages the blood-brain barrier (52). And extreme stress has been shown to increase inflammation and increase the permeability of the blood-brain barrier (53-55). But normalizing your stress levels can help the blood-brain barrier repair itself.

The blood brain barrier in human matures at an early age (4months) .

Small, lipid-soluble agents, such as antidepressants, cross the BBB via diffusion through endothelial cells. 3. Specialised transport proteins transport glucose, amino acids, and drugs like vinca alkaloids and cyclosporin, across the BBB.

Brain inflammation, oxidative stress, and genetic factors all contribute to this disease [49]. Blood-brain barrier dysfunction is also connected to schizophrenia. The oxidative damage and inflammation that causes schizophrenia also damages the blood-brain barrier (BBB) [49].