# State-of-All-the-Art and Prospective Hydrogel-Based Transdermal Drug Delivery Systems
## 3 Fundamentals of Hydrogels
### Types of Hydrogels
#### 3.2.1 Classification Based on Source Origin
Another significant category of hydrogels is multipolymer interpenetrating polymeric hydrogels (IPN). These hydrogels consist of two crosslinked components, either synthetic or natural polymers, interwoven into a network structure. Hydrogels of this kind exhibit distinctive properties stemming from the interpenetration of the polymer networks. With appropriate combinations of polymers, IPNs may have improved mechanical strength, stability, biocompatibility, etc. Natural hydrogels are hindered by significant drawbacks, including insufficient mechanical robustness, inconsistencies between batches, and the risk of disease transmission, particularly with animal-derived hydrogels [29]. In contrast, synthetic hydrogels often require alterations because they may not be as biocompatible and can degrade more slowly than natural hydrogels. Depending solely on natural or synthetic hydrogels can limit their use in scenarios that demand exact control over physical characteristics and smooth biological integration [29]. Classification of Hydrogels Based on Charge and Composition  
Hydrogels can be categorized into ionic types (anionic, cationic), nonionic, and ampholytic based on their charge. Ionic hydrogels exhibit pH sensitivity, attributed to the inclusion of carboxyl, amine, or sulfonic groups. A few notable examples are PMAA, PDMAEMA, and PAA used in synthetic hydrogels. Physical or chemical crosslinking of cations and anions forms ampholytic hydrogels [33]. A well-known ampholytic hydrogel is prepared by copolymerizing two monomers, [(methacrylamide)propyl] trimethylammonium chloride (MAPTAC) and sodium styrene sulfonate (SSS), with acrylamide [34]. Classification Based on External Stimuli Response  
Another significant categorization of hydrogels is determined by their responsiveness to external stimuli. These stimuli encompass pH, temperature, light, magnetism, electric fields, enzymes, glucose, and more. This classification is especially valuable in regulating the controlled release of drugs by adjusting external stimuli factors. pH-sensitive polymers either accept or release protons depending on the pH of the surrounding tissues [11]. This establishes the foundation for the swelling and release of drugs in a pH-sensitive environment. Thermosensitive hydrogels undergo a transition from solution to gel at a specific critical temperature. By adjusting the fluid temperature, the swelling characteristics of hydrogels can be modified [11]. Electric-responsive hydrogels are electroactive polymers that change size with electric field application. The presence of an electric field is generally found to increase drug release compared to the passive state [11]. Light-responsive hydrogels are also extensively used for many applications. The primary objective of managing drug delivery is to optimize the rate of release, ensuring that the drug remains within a therapeutic range by precisely targeting tissues and cells while minimizing potential side effects [35]. Several recent studies have focused on developing NIR-responsive hydrogel patches for transdermal drug delivery. An advantage of NIR-based hydrogel systems is their ability to shield drugs from thermal degradation, achieved through the implementation of cascade stimuli to regulate drug release. This feature proves especially beneficial for delivering temperature-sensitive proteins such as antibodies [35]. In a study by [PERSON] et al., drug-loaded electrospun fibers were shown to offer sustained release of drugs, with the added capability of providing an on-demand dose when exposed to NIR-light stimulation [35]. [PERSON] et al. designed a topical hydrogel patch for nanomaterial-assisted photothermal therapeutics, as well as for on-demand drug delivery applications. The patch exhibited photothermal stability for four cycles under cyclic photothermal heating. Addition of the patch was demonstrated to be a viable solution for the pH-sensitive hydrogels.