**Abstract**

Due to their unique physical and chemical properties, hydrogels have attracted significant attention in several medical fields, specifically, drug delivery applications in which gel-based nanocarriers deliver drug molecules to the region of interest in biological organs. For different drug delivery applications, hydrogel systems can be manipulated to provide passive and/or active delivery. Thus, several drug targeting, loading, and releasing mechanisms have been devised and reported in the literature. This chapter discusses these mechanisms and their efficacy with respect to different drug delivery applications. Furthermore, the drug dosage is dependent on the design and shape of the hydrogel systems, which in turn depend on the route of the drug administration. This chapter covers the types of hydrogel-based products applied via different routes of drug administration. Lastly, this chapter addresses different classifications of delivered drugs including small molecular weight drugs; therapeutic proteins and peptides; and vaccines.

**Keywords:** drug delivery, loading, targeting, releasing, routes of administration

### **1. Introduction**

Hydrogels are three-dimensional polymeric networks that are utilized in various medical applications due to their unique properties: hydrophilicity, biodegradability, non-toxicity, and their controllable mechanical properties to mimic the mechanics of biological tissues [1, 2]. Furthermore, their structural properties exhibit similarities with biological extracellular matrix components which makes them ideal for cell culture and growth [3].

From the mechanical perspective, the concentration of the polymer network in hydrogels controls, to large extent, their mechanical strength allowing them to mimic the mechanics of physiologically loaded tissues [4]. Consequently, due to their availability and relatively low cost, hydrogels have become an attractive option when developing quantitative techniques that measure the mechanics of biological tissues [5–8].

On structural level, hydrogels can be produced by chemical or physical crosslinking. In chemical (permanent) hydrogels, the network is crosslinked with strong covalent bonds that connect the molecular chains [9]. In physical (reversable) hydrogels, the gel's molecular chains are connected with weaker forces such as hydrogen-bonding and ionic forces, thus, they can be easily dissolved by altering their environmental conditions (e.g., temperature, ionic strength, or pH of the gels [10]). These crosslinking methods allow the synthesis of multi-network hydrogels. For instance, hydrogels can be fabricated to have highly crosslinked rigid chains that are entangled with weakly crosslinked chains to provide a functional network system used in synthesizing biomaterials for several medical applications [11, 12].

One of the medical applications the hydrogels used in is contact lenses, mainly due to their unique physical properties and ease of processing; for example, Bauman et al. [13] developed Silicone Hydrogel lenses with nano-textured surface that mimics the surface of human cornea. Hydrogel lenses are also known for their wettability, a property necessary to avoid tear deposits [10], thanks to plasma treatment during the synthesis process [14]. Gas permeability is also a key characteristic of contact lenses to provide the cornea with efficient supply of oxygen at sufficient rates. Hydrogel lenses can be designed to meet this requirement thanks to their hydrated polymer matrix [10]. Hydrogels are also commonly used in wound dressing; they have been used in combination with other materials to form composite products efficient for different dressing applications; for example, a gauze impregnated with thermoplastic hydrogels allows for absorbing wound exudate while maintaining relative slimy consistency, as a result, it prevents adherence to the wound that normally results in pain during gauze changes [15]. Moreover, flexibility and transparency of hydrogels also made them an attractive option in wound dressing. While flexibility facilitates easy removal of the dressing products, transparency allows for continuous observation of the wound healing process [16].

Nowadays, delivery and release of drug molecules is receiving significant attention in many fields of medicine in which therapeutic drugs are loaded in polymerbased-carriers. These carriers transport the drugs to the targeted location [17, 18]. The efficacy of gels as drug-carriers relies in their adjustable porosity through controlling the crosslinking density of their matrix. Their porous structure allows for drug loading and releasing with high efficiency [19, 20]. Numerous studies have been published on the potential applications of hydrogels in drug delivery focusing on their mechanism, shape of the gel-carriers, and types of transported drugs. Therefore, this chapter, will discuss different drug loading and releasing mechanisms with respect to their corresponding medical application. Furthermore, the drug dosage is dependent on the design of the hydrogel systems, which in turn depend on the route of the drug administration (e.g., rectal, ocular, peroral, etc.), thus, this chapter will shed the light on the types of hydrogel-based carriers applied via different routes of drug administration. Lastly, this chapter will cover different classifications of the delivered drugs using gel-based delivery systems including small molecular weight drugs; therapeutic proteins and peptides; and vaccines.
