Nanoparticles for Therapeutic Vehicles-Hydrogels

Hydrogel is a polymer network system with a hydrophilic three-dimensional network cross-linked structure. It has a soft shape and maintains a specific shape, can absorb a large amount of water, and has improved mechanical properties, as well as good biocompatibility and biodegradability. Since the preparation was proposed by researchers in the 1950s, it has been widely used in various fields, such as tissue engineering, drug delivery, 3D cell culture and other medical fields.

Over the years, people have defined hydrogels at different levels. Over the years, people have defined hydrogels at different levels. One of the most common claims is that hydrogels are a network structure formed by cross-linking and swelling with water by one or more monomers through simple reactions. Another argument is that hydrogel is a polymer material, which has the ability to swell with water and can store a large amount of water inside its structure, and the material itself does not dissolve in water. In the past few decades, hydrogel has received great attention because it has shown extraordinary application potential in various fields. Hydrogel is rich in water and has good flexibility. This property makes it very close to biological tissues, thus creating a huge application value in the biological field. The polymer skeleton that constitutes the hydrogel network cross-linked structure contains a part of hydrophobic groups and a part of hydrophilic groups. The hydrophilic groups can bind to water molecules and make it have strong water-locking ability. The presence of hydrophobic groups makes the hydrogel have the property of swelling in water, and the cross-linking between the polymer skeletons causes the hydrogel to maintain a three-dimensional structure in water without dissolving.

In the past two decades, natural hydrogels have been gradually replaced by synthetic hydrogels, because synthetic hydrogels have longer use time, higher water-holding capacity and stronger mechanical properties. In addition, the synthetic polymer has a clear structure and is easier to functionally modify according to specific applications.

Classification of Hydrogels

There are many types of hydrogels, and hydrogels can be classified according to the source of their raw materials, the cross-linking method of the polymer network, the nature of the cross-linking chemical bonds, the size and shape of the hydrogel, and so on. According to the source of the gel-forming components of the hydrogel, hydrogels can be divided into synthetic polymer hydrogels and natural component hydrogels. Natural hydrogels are prepared from natural products of agar, protein, DNA, etc.; synthetic hydrogels are formed by cross-linking synthetic polymers. According to the size of the hydrogel, hydrogels can be divided into microscopic hydrogels and macroscopic hydrogels. Among them, macroscopic hydrogels can be divided into columnar, fibrous, membrane, spherical and so on. Microscopic hydrogels are divided into nanometer and micrometer sizes. According to the response of hydrogels to external environmental stimuli, hydrogels can be divided into environmentally sensitive hydrogels and traditional hydrogels. Traditional hydrogels cannot respond to environmental changes, such as temperature, light, pH, electric field, etc. The environmentally sensitive hydrogel itself can feel subtle changes in the external environment, and produce certain physical and chemical changes, and even macroscopically visible changes in shape. According to the nature of the chemical bonds of the cross-linked structure when the hydrogel is gelled, the hydrogel can be divided into a chemical gel and a physical gel. If the primary or secondary chemical bonds that form gels in the hydrogel system are composed of ions, hydrogen bonds, or hydrophobic interactions, such hydrogels are called reversible hydrogels or physical gels. Physical gels are usually reversible. By changing the external environment in which the hydrogel is located, such as pH, ionic strength, or temperature, the hydrogel can undergo a phase transition. Another type of hydrogel is called chemical gel or permanent hydrogel. In the gel-forming network of this type of hydrogel, covalent bonds play a vital role. This type of hydrogel may or may not be charged. The charge depends on the nature of the polymer in the gel-forming network. Charged hydrogels usually swell when the pH changes. Of course, if they are exposed to an electric field, they will also change shape.

Nano Hydrogel Drug Delivery System

Nano-hydrogels are nano-sized hydrogels, which have the advantages of macro-hydrogels and nano-particle systems. Due to the advantages of good stability, high drug loading efficiency, long drug release cycle and functionalization, nanohydrogels have become a rapidly developing type of drug carrier materials in recent years.

Nanoparticles for Therapeutic Vehicles-Hydrogels

Figure 1. Nano hydrogels can help drugs break through the blood vessel barrier.

Nano hydrogels can use polymer networks to protect drugs, and have the advantages of good biocompatibility of hydrogels. At the same time, modified nano hydrogels can respond to environmental stimuli, making nano hydrogels an excellent class of Drug-loaded delivery system. Due to the smaller nano-sized structure, it has greater advantages than macroscopic hydrogels in some aspects. First of all, the smaller nano size facilitates the passage of nano hydrogels through the digestive system and human blood circulation system, and at the same time easily traverses some biological barriers to deliver the drug to the designated lesion site. Secondly, polymer nanohydrogels are simple to prepare, have good biocompatibility, and have a larger specific surface area to load more anticancer drugs, while protecting the drugs from being damaged by the complex external environment during the delivery process. More importantly, the design of nano hydrogels, such as the targeted modification of the surface of the nano hydrogels, or the design of the internal structure, makes the prepared nano hydrogel drug delivery systems have good targeting capabilities. At the same time, it responds irritatingly to changes in the chemical environment of the lesion. Therefore, in recent decades, extensive research has been conducted on nanohydrogels as drug delivery systems, and great research results have been achieved. As a drug-carrying delivery system, nanohydrogels are generally used to load a class of common anti-cancer drugs that are easily biodegradable, short half-lives, and lack targeting, such as nucleic acids, protein drugs, and common chemical drugs.

1. Dai T., et al.; A nanocomposite hydrogel with potent and broad-spectrum antibacterial activity. ACS Applied Materials & Interfaces. 2018, 10: 15163-15173.
2. Wang X. et al.; A polydopamine nanoparticle-knotted poly (ethylene glycol) hydrogel for on-demand drug delivery and chemo-photothermal therapy. Chemistry of Materials. 2017, 29:  1370-1376.
3. Bhattarai N, et al.; Chitosan-based hydrogels for controlled, localized drug delivery. Adv Drug Deliver Rev. 2010; 62:83-99.
4. R.Q. Liu, et al.; Tough and highly stretchable graphene oxide/polyacrylamide nanocomposite hydrogels. J. Mater. Chem. 2012, 22(28): 14160-14167.
5. Basak S, et al.; Multi-stimuli responsive self-healing metallo-hydrogels: tuning of the gel recovery property. Chem Commun. 2014, 50:2356-23569.

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