Transdermal delivery of active ingredients and drugs is an attractive and promising alternative to conventional administration routes, such as oral or parenteral. Transdermal delivery consists in the transport of active ingredients through the skin directly to the bloodstream. This method is applicable to small hydrophobic and hydrophilic moleculesand macromolecules. Indeed, this route of administration offers numerous advantages over conventional ones:

It is non-invasive and painless, it excludes the risk of infection, with a consequent improvement in patient compliance;

Keeps drug levels in the blood constant, eliminating the plasma peaks associated with oral and injectable administration;

It avoids the gastrointestinal tract and the hepatic first-pass metabolism, with the possibility of reducing the amount of drug being administered and systemic side effects.

However, few molecules have been used successfully transdermally to date, mainly due to the stratum corneum, which forms a barrier to the penetration of hydrophilic drugs, in particular to macromolecules such as proteins, peptides and vaccines. Consequently, research is currently being conducted, focusing on approaches that can overcome the skin barrier, with physical penetration enhancers such as microneedle patches.

A further evolution at the experimental stage are substances capable of modifying the secondary structure of keratin in the stratum corneum, making these skin proteins less organized and enabling enhancement of drug penetration via the transdermal route.

Since their physical properties are similar to those of human tissues for softness, flexibility and water content, hydrogels are used as carriers by various routes of administration. Among these, an important experimental direction in the near future is trans dermal delivery of drugs and active ingredients.

Hydrogels can be transformed into three-dimensional networks capable of absorbing large quantities of water or biological fluids using specific crosslinking techniques that add reversible cross-links or irreversible covalent bonds within the hydrogel.

This type of cross-links in the polymer structure produces insoluble bio-materials, capable of swelling in aqueous environments, retaining a significant fraction of water within their structure. This technology is extremely interesting as it allows hydrogels to hydrate up to thousand times more than their dry weight.

Evolution of these concepts has led to transformations of the initial material with changes in the functions and final properties of the product, and recently, to the creation of responsive hydrogels for the so-called “smart” materials, i.e., biomaterials capable of reacting to various environmental stimuli such as temperature, pH, light, sound, etc.

A further very important evolution in medicine and biomedical engineering is the spontaneous degradation of the hydrogel once its carrier function is completed. It is for this reason that polymer and crosslinking techniques, which enable spontaneous resorption of the hydrogel carrier, are preferred.

Some of the most popular current experimental methods of producing hydrogels with carrier function for transdermal delivery are those obtained by radiation, where gelation occurs via ion exchange with divalent cations, as in the case of alginate, capable of forming cationic bridges between adjacent molecules, the freezing-thawing method of some polymers such as vinyl alcohol, and/or physically cross-linking hydrogels through hydrophobic modification.

To date, all these methods have shortcomings as they produce unstable hydrogels due to the nature of the cross-links between the chains and are therefore, unsatisfactory as dosage and penetration of active ingredients remains difficult to manage.

Animprovement can be obtained with chemical crosslinking, which can establish more stable covalent bonds with the functional groups of polymers. However, a significant disadvantage of chemical crosslinking is the toxicity of residual crosslinking agents, which remain within the polymer itself.

Bioitech has developed a platform based on chemical crosslinking capable oflimiting reactive residues at levels below 0.1 part per million, even at initial polymer concentrations of 100 mg/g. On this basis, the Bioitech research center is actively involved in studies of trans-dermal delivery of active ingredients, such as the trans-dermal release of insulin and vaccines.