**3. Hydrogel administration**

Besides long-term stability and release properties, passing the toxicity screening is essential for hydrogel formulations to be used in drug delivery. This is mainly due to the rise of inflammatory reactions that occur as a result of the degradation of synthetic polymers [52]. Therefore, achieving biocompatibility is necessary to use hydrogels in an environment of living organisms. Most in-vivo tests are conducted on animal models to provide reliable biomedical mimicry. As a result, several

hydrogel-based drug delivery systems have been developed and approved for clinical use through different administration routes. Currently, the common accessible routes of these systems are Oral [53], rectal [54], subcutaneous [55], transdermal [56], ocular [57], and intraperitoneal [58]. These administration routes are illustrated in **Figure 3**. **Table 1** provides examples of gel-based products used in drug delivery through different administration routes.
