Focus On Nanotechnology: A Brief Overview of Important Nanomaterials and Their Diverse Uses

Introduced in 1991, solid lipid nanoparticles (SLN) are an alternative to conventional colloidal carriers like emulsions, liposomes, and polymeric micro and nanoparticles. Solid-based nanoparticles are garnering significant interest as a novel colloidal drug carrier for intravenous applications because they have been suggested as an alternative particulate carrier system. Sub-micron colloidal carriers (SLN) are made of physiological lipid and are distributed in water or an aqueous surfactant solution. They have a diameter of 50 to 1000 nm. Small size, high drug loading, vast surface area, and phase interaction at the interface are some of the special qualities that SLN offer. They are also appealing because of their potential to enhance pharmacological performance ^[36]. SLNs have a mean diameter of 50–1000 nm and are morphologically spherical, smooth surfaces. Both behaviors in vitro and in vivo rely on how SLNs are physicochemically characterized (Fig. 1)^[1].

Fig. 1: Structure of SLNs ^[1]

Nano-formulations include drug particles at the nanoscale that are made with nanotechnology or have been integrated with nano-formulations to provide a revolutionary drug delivery system. In the 1960s, nano-formulation began to be used in the pharmacological and medical domains (fig. 2) ^[3].

A very versatile family of nanocarriers, lipid-based nanoparticles (LNAPs) have become widely used in pharmacology and medical research [4]. The main obstacle to medication administration in the posterior portion is the blood-retinal barrier. The most popular and straightforward method of delivering medication to the anterior segment is topical administration, similar to eye drops ^[4].  Nanoemulsions (NEs) are colloidal dispersions that are nanometers in size. They usually consist of an oil phase that is dispersed in an aqueous phase (oil-in-water, O/W) or vice versa (water-in-oil, W/O). Bicontinuous and multiple NEs (MNEs) are examples of additional categories, such as oil-in-water (O/W/O) or water-in-oil-in-water (W/O/W) ^[21]. In the nanoscale size range, nanogels are three-dimensional hydrogel materials made of networks of crosslinked, swellable polymers that have a high capacity to retain water without truly dissolving in the aqueous medium. Their architecture's adaptability permits the addition of a wide variety of guest molecules, from inorganic nanoparticles to biomacromolecules like proteins and DNA, with the appropriate adjustments to the materials used in their production, all without affecting their gel-like properties ^[34]. Nanogels (NGs) for drug delivery, gene therapy, and nanohydrogels have been developed as a result of recent developments in nanomedicine. They are appropriate for biomedical applications since they are frequently biocompatible. Hydrogels come in a wide range of sizes, from a few micrometers to several centimeters, and are employed in a variety of fields, including bandages, tissue engineering, cosmetics, and medical equipment^[26]. There are currently only 15 cancer medications based on nanoparticles available on the market, compared to decades before. Limited scalability, inadequate control over reaction parameters, nanoparticle polydispersity, inadequate batch-to-batch repeatability, and high chemical reagent volumes—including pharmaceuticals—are the hurdles in nanoparticle translation^[26]. Depending on their intended uses and desired characteristics, nanogels can be made of a wide range of natural or synthetic polymers. The following are examples of natural polymers: (a) chitosan, which is derived from chitin and is known for its antimicrobial, biocompatible, and biodegradable qualities; (b) alginate, which is extracted from algae and is valued for its ability to form gels in the presence of divalent ions like calcium; (c) hyaluronic acid, which is a naturally occurring component of the extracellular matrix and is chosen for its highly effective water retention; and (d) polysaccharides, such as those found in natural gums^[23].
Nanogels are non-toxic to the tissue microenvironment and exhibit extremely high stability in physiological fluids^[26] Because of their robustness and similarity to human tissues, they are able to withstand shear forces and blood serum proteins. Table 1 lists the most current systems based on nanogel technology, demonstrating its multifunctional qualities that are beneficial for a range of illnesses ^[26].

1. Solid-Lipid Nanoparticles (SLNs)

Three major forms of SLNs can be distinguished based on drug loading: ^[40,41]

1. Homogeneous matrix
2. Drug-enriched shell
3. Drug-enriched core

Through careful formulation procedures like high-pressure homogenization above the lipid melting point or cold homogenization methods, the homogeneous matrix model exhibits a uniform distribution of drug molecules spread throughout the solid lipid core. In addition to improving therapeutic efficacy and stability by avoiding crystallization or phase separation, this strategy guarantees consistent drug encapsulation and controlled sustained release. It is especially well-suited for uses that call for enhanced bioavailability and sustained pharmacological activity. Conversely, the outer shell of the nanoparticles is where the drug is mostly concentrated in the drug-enriched shell model. While the drug becomes enriched and trapped in the solid-lipid outer shell, which subsequently hardens and encapsulates the drug on the surface, the lipid core of a hot lipid nano-emulsion initially solidifies during cooling. Although it might not be as suitable for prolonged release, this design offers quick or burst release, which is beneficial in situations requiring focused administration or an instant therapeutic effect. The inner core of the nanoparticles contained a high concentration of the drug, according to the drug-enriched core model. Before lipid recrystallization, drug molecules precipitate inside the lipid matrix when it cools, creating a drug-rich core encased in a protective lipid shell. By demonstrating drug diffusion across the lipid barrier, this arrangement protects delicate medications and offers extended, regulated release. It is perfect for treatments that call for prolonged drug release patterns and defense against degradation of the active ingredient; see figure 4. ^{[40, 41, 52, 50]}

2. Nanogels

The classification of nanogels is mentioned in Fig. 4^[24]

1. Nanogels are categorized based on their structural properties.

Fig. 5 lists the different kinds of nanogels. ^[24]

1. Hollow nanogels:

An empty core cavity is part of the structure of hollow nanogels. Core-shell particles (such as silica, gold, and HPC) are used in the creation of hollow nanogels, and the core is then removed (either by solvent precipitation or a pH gradient). Large surface area and a hollow interior for loading or trapping are two benefits of hollow nanogels.

2. Multilayered nanogels:

 Multiple layers of one or more polymers make up the structure of these nanogels. Sequential polymer layering,  occasionally with crosslinking, is the preparation method. Its benefits include a high site specificity, a customizable drug release profile, and suitability for highly potent or fragile medications.

3. Core-shell nanogels

Metal, a nanorod, and a carbon-based nanomaterial make up the structure. The polymeric or organic shell encloses the center. Functional characteristics like optical, magnetic, and conductive are provided by the core, while the shell manages stability and release.

4. Hairy nanogels

This nanogel's structure consists of surface-grafted, hair-like polymer chains, sometimes referred to as polymer brushes. It is prepared via controlled radical polymerization techniques or macro-RAFT agents ^[24].

2. Nanogels are categorized according to how responsive they are to different environmental stimuli.

1. When non-responsive nanogels come into contact with aqueous fluids, they swell through simple absorption, removing the need for external triggers to continuously release medications at the desired site.
2. sensitive nanogels, in response to changes in electrical power, pH, light, magnetic field, ultrasound, ion strength, or solvent composition. It is possible for responsive nanogels to swell or deswell. These stimuli Both natural and synthetic polymers are commonly used to create responsive nanogels, which have a remarkable capacity to absorb water and swell in response to a variety of physical, chemical, and biological stimuli. Nanogels that react to many stimuli are referred to as multi-responsive nanogels. Because of their ability to undergo reverse expansion and deswelling in response to various triggers, responsive nanogels are a valuable substrate for biomedical applications. Targeted and controlled drug delivery is made possible by this feature.

3. Linkage-based nanogels:

1. non-covalent linkage

Ionic, surface/interface, adsorption, and van der Waals forces are examples of self-assembled interactions that don't        require cross-linking agents. They don't need chemical reagents to lessen toxicity because this kind of connection is reversible. It enables regulated release and dynamic responses. However, it is unstable and quite weak. For example,    micellar nanogels, liposome-modified nanogels, and physically cross-linked nanogels.

2. Covalent Linkage ^[24]

Its stable bonds indicate that the coupling is stoichiometrically controlled and permanent. They have stable structures and a high mechanical strength. Their qualities are precisely tuned and they are resilient. Additionally, they are helpful for stimuli-responsive or regulated release.

4. Polymer-based nanogels:

Drug delivery systems based on oligosaccharide-based nanogels are becoming more popular due to their safety, biodegradability, and ease of modification. Usually created by the interaction of naturally occurring polymers with positive and negative charges, they are able to react to variations in the pH of the body. For example, without the need for additional surfactants, chitosan nanogels serve as natural emulsion stabilizers. They can also be cross-linked to increase their stability for medicinal applications. Pullulan nanogels are useful in drug and protein delivery because they are very effective at preventing proteins from clumping or breaking down, especially when modified with cholesterol^[37,38].

Particularly intriguing are hyaluronic acid (HA) nanogels, which have the inherent capacity to target particular cells due to their natural binding to the CD44 receptor, which is present on the surface of many cells. Alginate nanogels are especially effective in protecting delicate proteins during oral delivery, even in the stomach's acidic environment, and they may be chemically altered to change how they dissolve. Utilizing its donut-like shape, cyclodextrin nanogels enhance the solubility of hydrophobic medicinal molecules by trapping and transporting them. Last but not least, gum acacia nanogels, which are derived from the natural gum of acacia trees, are affordable, environmentally benign, and extremely soluble in water. As such, they may be readily combined with other polymers, such as chitosan, to deliver drugs. All things considered, these various varieties of polysaccharide nanogels demonstrate how natural materials can be transformed into an excellent instrument for safer, more effective, and targeted treatments. ^[43]

3.  Nanoemulsions

Types of Nanoemusion: ^[44,52]

1. Oil-in-water
2. Water-in-oil
3. Biocontinuous

Emulsions represent an important class of pharmaceutical dosage forms in which one liquid is dispersed as small droplets within another immiscible liquid, stabilized with the aid of emulsifying agents. Their significance in pharmacy arises from their ability to improve drug solubility, mask unpleasant taste, enhance absorption, and permit controlled drug release. pharmaceutical emulsions may be oil-in-water(O/W) or water-in-oil (W/O), with their application ranging from oral, topical, and parenteral delivery to cosmetics to conventional emulsions, advanced systems such as nanoemulsions and microemulsions have gained increasing attention due to their small droplet size, high stability, and improved bioavailability of poorly soluble drugs. ^[46,47]

With droplet sizes of less than 200 nm, nanoemulsions are kinetically stable but thermodynamically unstable dispersions that are primarily categorized by their composition and dispersed phase type. Oil-in-water (O/W) nanoemulsions, in which oil droplets are distributed throughout an aqueous phase, are the three main varieties.^[35,36]

frequently used to increase the solubility and absorption of lipophilic drugs; bicontinuous nanoemulsions, where both the water and oil domains interpenetrate and provide benefits in solubilizing both hydrophilic and lipophilic drugs; and water-in-oil (W/O) nanoemusions, where water droplets are distributed in a continuous oil phase and are frequently used in topical, cosmetic, and transdermal applications. Each kind has distinct biological and physical characteristics that affect its stability, drug release profile, and potential for use in pharmaceuticals. Nanoemulsions are extremely adaptable carriers in modern pharmacy because they may be customized for oral, parenteral, or topical administration systems by carefully choosing the formulation components. ^{[45,46,51,52]}

4. Nanoparticles

Nanoparticles are classified into three main types:

1. Organic nanoparticles
2. Inorganic nanoparticles
3. Carbon-based nanoparticles

1. Organic nanoparticles (ONPs)

ONPs are made from organic compounds and are less than 100 nm. Ferritin, micelles, dendrimers, and liposomes are a few examples; many of them are hollow nanocapsules that can transport medications. Their primary benefits-biodegradability, non-toxicity, and light and heat responsiveness-make them ideal for use in biomedicine. Particle size, surface form, stability, and drug-loading techniques (entrapped or absorbed) all affect how well they transport drugs. ONPs are frequently utilized in regulated and targeted drug delivery systems due to their ability to target particular bodily areas ^[48,49].

2. Inorganic nanoparticles The structure of inorganic nanoparticles is made up of carbon atoms and metals or metal oxides. Due to quantum confinement and coulomb charge effects, they exhibit distinct quantum size effects, high surface-to-volume ratios, size-dependent characteristics, and optical behaviors that are very different from those of bulk materials ^[49].

1. Metal- based nanoparticles

Gold, silver, copper, iron, zinc, and cobalt are among the elements that can be used to create metal nanoparticles, which have remarkable electrical, thermal, antibacterial, and catalytic capabilities. Surface behavior is improved by their nanoscale size. These nanoparticles, which have customizable size and shape, are used in environmental sensing, chemical catalysis, and biological imaging because of their potent surface activity and quantum phenomena. ^[49]

2. Metal oxide-based nanoparticles. Because they are more stable, reactive, and efficient than their metallic counterparts, metal oxide nanoparticles (such as TiO2, ZnO, SiO2, and Al2O3) are being researched extensively. Strong electrostatic connections are created when positive metal ions and negative oxygen ions interact ionically to generate them. Iron nanoparticles, for example, easily oxidize to Fe2O3, which increases their reactivity. Metal oxides are employed in photocatalysis, energy storage, sensors, and catalysis due to their functional characteristics and chemical stability.^[48,49]

3. Carbon based nanoparticles

Carbon-based nanoparticles have special electrical, thermal, and structural characteristics. They are made from carbon allotropes such as graphite, diamond, graphene, carbon nanotubes (CNTs), and fullerens. Their strong covalent structures and adaptable bonding enable them to be used in biological, electronics, energy storage, and water treatment applications. While CNTs and activated carbon are useful for adsorption, catalysis, and separation processes, graphene, a single-atom-thick sheet with exceptional strength and conductivity, is used as a building block for other carbon nanostructures. ^[48]

a) Fullerenes

Buckminsterfullerene (C60), in particular, is a spherical carbon molecule made up of 60 carbon atoms put in a cage-like structure that resembles a soccer ball. They have special physicochemical characteristics due to their symmetrical geometry and resonance stabilization. Derivatives of C60, including nanorods, nanotubes, and nanosheets, are utilized in material science, catalysis, and nanoscience. Applications in medication delivery, polymer development, and environmental cleanup are made possible by their capacity to undergo covalent and supermolecular modifications. ^[48,49]

 b) Graphene and graphene oxide

 Graphene and its derivative, graphene oxide (GO), have shown great promise in the creation of polymer-based nanocomposites because of its exceptional barrier qualities, electrical conductivity, and mechanical strength. Although pure graphene has many benefits, its large-scale use is hampered by issues including agglomeration, poor solubility, and the complexity of bottom-up synthesis. Conversely, GO is easily synthesized from carbon sources using top-down techniques, and because it contains functional groups that contain oxygen, it has great solubility and may effectively modify its surface. These characteristics improve GO dispersion in polymer matrices, which raises the overall effectiveness of nanocomposites. Furthermore, GO's sp2-hybridized carbon network effectively blocks gas diffusion, which makes it ideal for use in innovative packaging materials, corrosion resistance, and protective coatings for delicate electronics. ^[48]

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