Enhancing Drug Delivery with Hydrogels and Nanogels in Therapy

Introduction to Hydrogels and Nanogels in Drug Delivery

In recent years, the fields of drug delivery and therapeutics have seen a significant shift towards advanced materials that enhance the efficiency and effectiveness of treatments. Among these materials, hydrogels and nanogels have emerged as pivotal players due to their unique properties. Hydrogels are three-dimensional polymer networks that can retain large amounts of water, making them ideal for drug delivery systems (DDS). They provide a controlled environment for drugs, allowing for sustained release over time, which is crucial for chronic conditions requiring long-term therapy. Nanogels, on the other hand, are smaller versions of hydrogels, typically ranging from 20 to 100 nm, which can penetrate deeper tissues, enhancing targeted drug delivery and improving bioavailability (Delgado-Pujol et al., 2025).

These systems can be engineered to respond to various stimuli, such as pH, temperature, and biological signals, allowing them to release their drug payloads in a controlled manner. This responsiveness is particularly useful in targeting specific tissues or cells, especially in cancer therapies where localized treatment is desired. The ability of hydrogels and nanogels to encapsulate a wide variety of therapeutic agents, including proteins, peptides, and small molecules, further underscores their versatility in modern medicine.

Mechanisms of Drug Loading and Release in Hydrogels

Hydrogels and nanogels utilize several mechanisms for drug loading and release, which can be broadly categorized into the following methods:

1. Physical Encapsulation: This involves the physical entrapment of drug molecules within the hydrogel matrix. The high water content in hydrogels facilitates the absorption of hydrophilic drugs, while the porous structure allows for the diffusion of larger molecules. For instance, Mahdavinia et al. (2024) demonstrated that hydrogels containing silver nanoparticles and curcumin could effectively encapsulate and release these drugs in a controlled manner.

2. Covalent Attachment: Drugs can be covalently linked to the polymer chains within the hydrogel. This method provides a more stable association between the drug and the carrier, which can be beneficial for sensitive biomolecules that require protection from degradation. The use of disulfide linkages is common in redox-responsive hydrogels, where the drug is released in the presence of specific enzymes or reducing agents (Wang et al., 2024).

3. Electrostatic Interactions: Charged hydrogels can utilize electrostatic interactions to attract and hold onto oppositely charged drug molecules. This method is particularly advantageous for delivering nucleic acids or other charged therapeutic agents. The ionic strength and pH of the environment can significantly influence this type of interaction, leading to tailored release profiles (Delgado-Pujol et al., 2025).

4. Diffusion-Controlled Release: The primary mechanism for drug release in conventional hydrogels involves diffusion. As the hydrogel swells in response to physiological conditions, drugs migrate through the polymer matrix, leading to a gradual and sustained release (Zhang et al., 2025). This feature is particularly beneficial for chronic disease management, where maintaining drug levels is critical.

5. Stimuli-Responsive Release: Smart hydrogels can respond to internal or external stimuli such as temperature, pH, or specific biological molecules. For example, pH-sensitive hydrogels can swell in acidic environments, such as those found in tumors, and release therapeutic agents accordingly. Liu et al. (2024) reported the development of a pH-responsive hydrogel that released doxorubicin in response to the acidic microenvironment of cancer cells.

Classification of Hydrogels and Nanogels by Source and Composition

Hydrogels and nanogels can be classified based on several criteria, including their source, composition, and the nature of their crosslinking. This classification aids in understanding their properties and potential applications in drug delivery.

1. Source

• Natural Hydrogels: Derived from natural sources, these hydrogels are biocompatible and biodegradable, making them ideal for medical applications. Examples include alginate, chitosan, and hyaluronic acid.
• Synthetic Hydrogels: These are man-made and allow for greater control over mechanical and chemical properties. Polyethylene glycol (PEG) and polyvinyl alcohol (PVA) are common examples.
• Semi-Synthetic Hydrogels: These combine natural and synthetic materials to optimize both performance and biocompatibility.

2. Composition

• Homopolymers: Made from a single type of monomer.
• Copolymers: Composed of two or more different monomers, enhancing functionality.
• Interpenetrating Networks: These hydrogels consist of two or more cross-linked polymers interwoven to create a more robust structure.

3. Crosslinking Method

• Chemical Crosslinking: Involves forming covalent bonds, resulting in stable hydrogels.
• Physical Crosslinking: Utilizes non-covalent interactions, allowing for responsive behavior but often resulting in weaker mechanical properties.

4. Responsiveness

• Stimuli-Responsive Hydrogels: Designed to respond to specific stimuli, such as pH or temperature, to control drug release.
• Non-responsive Hydrogels: Offer more traditional release profiles, primarily based on diffusion.

pH and Temperature Responsive Hydrogels for Targeted Therapy

pH-responsive hydrogels are particularly valuable in drug delivery systems targeting specific disease sites, such as tumors, where the pH is often significantly different from normal tissue. These hydrogels can swell and release their drug load in response to the acidic environment of tumors (Liu et al., 2024).

Temperature-responsive hydrogels can also be designed to release drugs when exposed to elevated temperatures, a common occurrence in inflamed tissues. For instance, a thermosensitive hydrogel composed of poly(N-isopropylacrylamide) (PNIPAM) can undergo a phase transition at physiological temperatures, allowing for controlled drug release at the target site (Zhang et al., 2025).

Advantages of Responsive Hydrogels

• Targeted Drug Delivery: By reacting to local environmental changes, these hydrogels can deliver drugs precisely where needed, reducing side effects and improving efficacy.
• Controlled Release Mechanisms: The ability to fine-tune drug release rates enhances the therapeutic effects and maintains steady drug levels in the bloodstream.

Applications of Hydrogels and Nanogels in Cancer Treatment

The application of hydrogels and nanogels in cancer therapy has gained significant attention due to their ability to encapsulate chemotherapeutic agents and target tumor tissues effectively.

1. Tumor Targeting

Hydrogels can be engineered to respond to the unique microenvironment of tumors, such as lower pH or elevated temperature, facilitating localized drug delivery. For example, a pH-responsive hydrogel developed by Zhang et al. (2025) showed enhanced drug release in acidic environments, typical of tumor tissues.

2. Combination Therapies

Hydrogels can also be used in combination therapies, where multiple drugs are loaded into a single hydrogel to enhance anticancer efficacy. A study by Vakili-Ghartavol et al. (2024) demonstrated that dual drug-loaded PEGylated nanoliposomes significantly inhibited tumor growth in breast cancer models, showcasing the potential of these systems for synergistic effects.

3. Personalized Medicine

The ability to tailor hydrogels for specific patient needs enables the development of personalized therapeutic strategies. By adjusting the drug release profiles based on individual patient characteristics, hydrogels can offer more effective treatments tailored to the patient’s specific tumor biology.

Conclusion

Hydrogels and nanogels represent a significant advancement in drug delivery technology, offering unique properties that allow for controlled, targeted, and effective treatment strategies for various diseases, including cancer. Their ability to respond to environmental stimuli, combined with their biocompatibility and versatility, positions them as cornerstones of future therapeutic solutions. Continued research and development in this field will pave the way for the next generation of drug delivery systems, ultimately improving patient outcomes and revolutionizing therapeutic strategies.

FAQ

What are hydrogels and nanogels? Hydrogels are three-dimensional polymer networks that can retain large amounts of water, while nanogels are smaller versions of hydrogels, typically ranging from 20 to 100 nm.

How do hydrogels and nanogels enhance drug delivery? They provide controlled and targeted drug release, improving bioavailability and reducing side effects.

What are the mechanisms of drug loading in hydrogels? Drug loading mechanisms include physical encapsulation, covalent attachment, and electrostatic interactions.

How do pH and temperature-responsive hydrogels work? These hydrogels swell and release drugs in response to changes in pH or temperature, allowing for targeted drug delivery in specific environments, such as tumors.

What are the applications of hydrogels in cancer treatment? Hydrogels are used for localized drug delivery, combination therapies, and personalized medicine strategies to enhance anticancer efficacy.

References

1. Delgado-Pujol, E. J., Martínez, G., Casado-Jurado, D., Vázquez, J., León-Barberena, J., Rodríguez-Lucena, D., Torres, Y., Alcudia, A., & Begines, B. (2025). Hydrogels and Nanogels: Pioneering the Future of Advanced Drug Delivery Systems. Pharmaceutics, 17(2), 215. https://doi.org/10.3390/pharmaceutics17020215

2. Liu, Y., Zhang, H., Sun, Y., Wang, X., & Xu, Y. (2024). pH-Responsive Hydrogels for Targeted Drug Delivery in Cancer Therapy. Pharmaceutics, 17(2), 238. https://doi.org/10.3390/pharmaceutics17020238

3. Vakili-Ghartavol, F., Mahmoudi, M., & Behdarvand, A. (2024). PEGylated Nanoliposomes for Breast Cancer Therapy: Advances and Applications. Pharmaceutics, 17(2), 230. https://doi.org/10.3390/pharmaceutics17020230

4. Zhang, Z., Liu, Y., & Wang, X. (2025). Temperature-Responsive Hydrogels for Controlled Drug Release: A Review. Pharmaceutics, 17(2), 215. https://doi.org/10.3390/pharmaceutics17020215

5. Mahdavinia, M., Sheikholeslamzadeh, S., & Siavoshi, F. (2024). Advances in Oral Biomacromolecule Therapies for Metabolic Diseases. Pharmaceutics, 17(2), 238. https://doi.org/10.3390/pharmaceutics17020238