Hydrogels with smart systems for delivery of hydrophobic drugs

ABSTRACT

Introduction: Smart hydrogel systems present opportunities to not only provide hydrophobic molecule encapsulation capability but to also respond to specific delivery routes.

Areas covered: An overview of the design principles, preparation methods and applications of hydrogel systems for delivery of hydrophobic drugs is given. It begins with a summary of the advantages of hydrogels as delivery vehicles over other approaches, particularly macromolecular nanocarriers, before proceeding to address the design and preparation strategies and chemistry involved, with a particular focus on the introduction of hydrophobic domains into (naturally) hydrophilic hydrogels. Finally, the applications in different delivery routes are discussed.

Expert opinion: Modifications to conventional hydrogels can endow them with the capability to carry hydrophobic drugs but other functions as well, such as the improved mechanical stability, which is important for long-term in vivo residence and/or self-healing properties useful for injectable delivery pathways. These modifications harness hydrophobic-hydrophobic forces, physical interactions and inclusion complexes. The lack of in-depth understanding of these interactions, currently limits more delicate and application-oriented designs. Increased efforts are needed in (i) understanding the interplay of gel formation and simultaneous drug loading; (ii) improving hydrogel systems with respect to their biosafety; and (iii) control over release mechanism and profile.

KEYWORDS:

• Hydrogels
• hydrophobic drugs
• hydrophobic domains
• drug delivery

Article highlights

• Hydrophobic drugs account for over 40% of marketed drugs and about 60% of the therapeutic compounds at the research and development stage.

• The hydrogel as a non-circulating and more stable carrier can to great extent overcome the constraints of polymeric containers to extend the duration of drug action and avoid repeated administration.

• In order to exploit the advantages of hydrogels for drug delivery and address their limitations in delivering incompatible hydrophobic drugs, different strategies have been adopted to modify the hydrogel system, including the introduction of hydrophobic domains, addition of nanoparticles and inclusion of cyclodextrin (CD) moieties.

• Hydrogel systems featuring pH-sensitive components together with hydrophobic domains can release the hydrophobic agents in response to the pH variation along GI tract.

• Minimally invasive injectable delivery of hydrophobic drugs can be achieved by thermo-sensitive in-situ gelling systems or self-healing mouldable hydrogels, with hydrophobic interactions, inclusion complexes or addition of nanoparticles.

• Hydrogel membranes are applied in transdermal drug delivery because of their minimal irritation to skin and the percutaneous adsorption of various hydrophobic drugs can be augmented via introduction of β-CD particles.

• A combination of research efforts is required to understand the physical interactions driving the hydrogel formation and hydrophobic drug loading, as well as to improve hydrogel systems using building blocks with lower biosafety concerns and to establish a variety of on-demand release mechanisms.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.