Hydrogels for drug delivery

19 June 2023

Hydrogels are three-dimensional, hydrophilic polymeric networks capable of absorbing large amounts of water or biological fluids. Due to their unique properties, such as high water content, biocompatibility, and tunable mechanical properties, hydrogels have emerged as a promising material for various biomedical applications, including drug delivery. In recent years, hydrogels have gained significant attention as drug carriers due to their ability to encapsulate and release a wide range of therapeutic agents, including small molecules, proteins, and nucleic acids. Here we take a look at the role of hydrogels in drug delivery.

Classification of Hydrogels

Hydrogels can be classified based on various criteria, such as their origin, physical structure, and ionic charge. Based on their origin, hydrogels can be categorized into natural, synthetic, and hybrid hydrogels. Natural hydrogels are derived from natural polymers, such as chitosan, alginate, and hyaluronic acid, while synthetic hydrogels are prepared from synthetic polymers, such as poly(ethylene glycol) (PEG), poly(vinyl alcohol) (PVA), poly(acrylic acid) (PAA) and self-assembling peptide hydrogels (SAPHs). Hybrid hydrogels are formed by combining natural and synthetic polymers, offering the advantages of both types of materials.

Based on their physical structure, hydrogels can be classified into homogeneous and heterogeneous hydrogels. Homogeneous hydrogels have a uniform distribution of polymer chains, while heterogeneous hydrogels consist of distinct regions with different properties, such as porosity and mechanical strength. Hydrogels can also be classified based on their ionic charge into nonionic, anionic, cationic, and amphoteric (a mixture of anionic and cationic regions) hydrogels.

Synthesis of Hydrogels

Hydrogels can be synthesized using various techniques, such as chemical crosslinking, physical crosslinking, and self-assembly. Chemical crosslinking involves the formation of covalent bonds between polymer chains, either through the reaction of functional groups present on the polymer or by using crosslinking agents. Physical crosslinking, on the other hand, relies on non-covalent interactions, such as hydrogen bonding, hydrophobic interactions, and ionic interactions, to form the hydrogel network. Self-assembly, seen for example in SAPHs, is a bottom-up approach in which hydrogels are formed through the spontaneous organization of individual polymer chains into a three-dimensional network.

Properties of Hydrogels

The properties of hydrogels, such as swelling behavior, mechanical strength, and biocompatibility, play a crucial role in determining their suitability for drug delivery applications. Swelling behavior refers to the ability of hydrogels to absorb water or biological fluids, which is essential for the encapsulation and release of therapeutic agents. The swelling behavior of hydrogels can be tuned by modifying factors such as polymer concentration, crosslinking density, and ionic strength.

Mechanical strength is another important property of hydrogels, as it affects their stability and integrity in the physiological environment. Hydrogels with tunable mechanical properties can be designed by adjusting parameters such as polymer type, crosslinking density, and the presence of reinforcing agents. Biocompatibility, notably the interaction with the immune system, is a critical factor for hydrogels intended for drug delivery, as it ensures minimal adverse effects on the surrounding tissues and cells. Importantly natural hydrogels generally exhibit excellent biocompatibility, while synthetic hydrogels can be tailored to achieve the desired level of biocompatibility by modifying their chemical composition and structure.

Applications of Hydrogels in Drug Delivery

Hydrogels have been extensively investigated for various drug delivery applications, including oral, transdermal, ocular, and injectable drug delivery systems.

Oral drug delivery: Hydrogels have been explored as carriers for the oral delivery of drugs, particularly for the controlled release of therapeutic agents in the gastrointestinal tract. Hydrogels can protect the encapsulated drugs from the harsh conditions of the stomach and release them in a controlled manner in the intestine, thereby improving their bioavailability and therapeutic efficacy.
Transdermal drug delivery: Hydrogels have been used as matrices for the transdermal delivery of drugs, offering advantages such as sustained drug release, improved patient compliance, and reduced side effects. Hydrogel-based transdermal patches can be designed to release drugs at a controlled rate, ensuring a constant drug concentration in the systemic circulation.
Ocular drug delivery: Hydrogels have been investigated as carriers for ocular drug delivery, providing sustained release of therapeutic agents and improved bioavailability in the eye. Hydrogel-based ocular inserts and contact lenses can be used to deliver drugs to the anterior and posterior segments of the eye, overcoming the limitations of conventional eye drops, such as rapid clearance and low drug penetration.
Injectable drug delivery: Injectable hydrogels have emerged as a promising platform for the localized and controlled delivery of drugs, particularly for the treatment of diseases such as cancer and diabetes. Injectable hydrogels can be administered using minimally invasive techniques, forming a depot at the injection site that releases the encapsulated drugs in a controlled manner over an extended period.