**4. Types of therapeutics delivered using hydrogels-based delivery systems**

#### **4.1 Small molecular weight drugs**

Budhian et al. [85] categorized the release of this class of drugs into three stages; (i) initial burst, during which the drugs immediately released into the medium; (ii) induction, in which the release of drugs is gradual; and (iii) slow release, in which the release reaches a steady slow rate [85]. These stages are controlled by three unique properties of the gel in use to synthesize the delivery systems: hydrophobicity, surface coating, and particle size [35]. The lower the hydrophobicity the higher the release of drugs during the burst stage; for example, the percentage of released drugs after 1 day is 45% for 220 nm strongly hydrophobic PLA particles, on the other hand, the release percentage is 70% for the same size of the moderately hydrophobic PLGA particles. The release stages are also affected by the surface coating of the nanoparticles; coating PLGA particles reduces the number of drugs released by 40%. The rate of release and the initial burst are affected by the size of the particles; increasing the size decreases the total surface area which reduces the burst period, furthermore, the larger the size, the longer the pathways the drug molecules take during the diffusion which increases the induction period [85].

#### **4.2 Therapeutic peptides and proteins**

Among several peptides- and proteins-based therapeutics that are used in drug delivery, enzymes are the most studied class of drugs [86]; examples of such enzymes include L-asparaginase, cysteine desulfatase, cysteine oxidase, arginase, and arginine decarboxylase [87]. Currently, only a few protein- and peptide-based drugs have been used in medicinal setting. The clinical use of this class of drugs is hindered by several factors: enzymatic degradation, renal filtration, inefficient cell entry, accumulation in nontargeted organs, immune system response that causes allergic reaction, and protein inactivation due to intrinsic properties such as low stability in an environment of physiological pH and temperature [88].

A simple approach to overcome the elimination of this class of drugs is introducing it via injection to the targeted organ. However, this strategy has its own limitations such as difficulty or delocation of the targeted site, drug toxicity, and long-term hospital setting administration [88]. Other delivery strategies were proposed such as microfabricated chips and implantable devices [89, 90]. While these strategies have shown promising results, their deployment and extraction require surgical intervention. To overcome these challenges and to stabilize the therapeutic proteins and peptides in the physiological environment, they are encapsulated into nanocarriers. This technique protects the enzymes from the degradation parameters imposed by the physiological environment while delivering different types of protein-based drugs [88].

Shimizu et al. [91] developed nanocarriers that efficiently encapsulates bone morphogenic proteins (BMPs), which have significant capability to convince bone formation. When BMPs are encapsulated by the developed nanocarriers, they provided sustained delivery of the BMPs over a time period of 14 days. In cancer therapy, polymersomes are used to deliver therapeutics; Danafar et al., 2016 investigated the delivery of drug molecules encapsulated into mPEG-PCL hydrogel nanocarriers in treating breast cancer. Their mPEG-PCL carriers provided suitable pH-dependent delivery of therapeutics to breast cancer cells [92].

*Hydrogel Biomaterials for Drug Delivery: Mechanisms, Design, and Drugs DOI: http://dx.doi.org/10.5772/intechopen.103156*


#### **Table 2.**

*Hydrogel-based delivery systems and their applications.*

#### **4.3 Vaccines**

Establishing an immunological memory and provoking sufficient immune response are the two primary factors that determine the efficacy of a vaccine delivery system [93, 94]. The main administration routes of vaccine delivery systems are parenteral and non-parenteral. The first is administered using hypodermic needles inserted through subcutaneous, intramuscular, and intradermal routes [95, 96]. On the other hand, non-parenteral delivery systems capitalize on needle-free devices such as jet injectors, liquid, powder, and polymeric (including hydrogel) systems [97]. In hydrogel-based systems, gel particles encapsulate the vaccine molecules and deliver it through intramuscular, oral, and transcutaneous routes [98, 99]. In recent years, different hydrogel delivery systems were developed to increase the efficiency of the vaccine delivery, **Table 2** summarizes these systems and their applications.
