# State-of-All-the-Art and Prospective Hydrogel-Based Transdermal Drug Delivery Systems
## 7 Challenges and Future Directions of Hydrogel-Based Transdermal Drug Delivery Systems  
Over recent decades, hydrogels have significantly progressed in their utilization within transdermal drug delivery systems. Despite these advancements, several challenges persist, impeding the full realization of hydrogel potential in this field. Among these challenges are drug loading, release control, skin permeation efficiency, long-term stability, and scalability constraints. The inherent limitation of hydrogels in accommodating high drug concentrations requires innovative approaches to enhance loading capacity without compromising the integrity of the matrix. Achieving controlled drug release rates necessitates precise control, prompting the development of responsive hydrogels that are sensitive to diverse stimuli such as temperature, pH, or enzymes.  
Addressing the ongoing challenge of improving skin barrier permeation efficiency while ensuring compatibility and minimizing irritation is crucial. Concerns also arise regarding the stability and durability of hydrogel-based systems over extended periods, particularly under diverse storage conditions, posing practical application hurdles. Additionally, challenges exist in scaling up production while maintaining uniformity, reproducibility, and cost-effectiveness.  
Future research directions aim to address these challenges. For instance, the development of smart hydrogels responsive to external stimuli like pH, temperature, or light can enable on-demand drug release, potentially enhancing therapeutic efficacy [102]. Additionally, exploring innovative drug-loading methods involving nanotechnology, molecular imprinting, or encapsulation techniques could significantly augment drug-loading capacity [103]. Moreover, leveraging hydrogels to deliver multiple drugs or combine them with nanoparticles or growth factors can revolutionize combination therapies.  
Customizing hydrogel formulations based on individual patient needs--considering skin type, dosage, and release kinetics--can elevate the effectiveness of transdermal therapies. Integration of advancements in 3D printing and nanotechnology to craft precise, patient-specific hydrogel structures holds the potential to revolutionize current methodologies in transdermal drug delivery. Consequently, meticulous design and utilization of hydrogel systems could open doors for a broad spectrum of applications within drug delivery. A recent study by [PERSON] et al. focused on ensuring a strong attachment between fibrous mats and plasmonic hydrogel layers in composites [104]. Plasmonic gold nanorods were integrated into polyacrylamide-based hydrogels as the hydrogel layer. The impact of crosslinking density on the integration of these two layers was investigated. Factors contributing to a more robust interface between the plasmonic hydrogel layer and electrospun nanofibers in multi-layer nanocomposites were explored [104]. By incorporating nanoparticles into hydrogels, their solid and adjustable optical responses can be utilized to manipulate photothermal effects upon exposure to external light. This combination holds promise for biomedical applications like biosensing and photothermal therapy [104].  
\begin{table}
\begin{tabular}{p{113.8 pt} p{113.8 pt} p{113.8 pt} p{113.8 pt}} \hline \hline
**Gel Type** & **Therapeutic/Drug** & **Application** & **Results** & **Reference** \\ \hline \multirow{6}{*}{Electrically Controlled \
\begin{tabular}{} \end{tabular} } & & & \(\bullet\) & Optimized drug release at 30 wt\% \\  & & & B.C. and increased with applying electrical potential. \\  & & Controlled anionic
\begin{tabular}{} \end{tabular} & \(\bullet\) & The highest amount of drug release was 78\%, which was obtained on a drug-loaded \\  & & For pain management applications & polypyrrole-incorporated \\  & & & composite under applied electrical potential at 7 V. \\  & & & \(\bullet\) & Exhibited remarkable benefit of antibacterial activity for gram-positive bacteria. \\ \hline \hline \end{tabular}
\end{table}
Table 6: _Cont._