Site-specific drug delivery in the skin for the localized treatment of skin diseases

ABSTRACT

Introduction: Due to the well-organized structure and barrier function of the skin, it is generally difficult for drugs applied directly on the surface of skin to reach their expected site of action. Accordingly, site-specific drug delivery in the skin has been increasingly explored to facilitate the treatment of skin diseases and reduce the systemic toxicity.

Area covered: An overview of the generally used sites for drug delivery in the skin is herein presented. Different strategies including particle-based carriers, physical technologies, and chemical approaches are discussed with regards to their potential application in site-specific drug delivery in the skin.

Expert opinion: Particle-based carriers are of particular significance for the enhancement of drug delivery in the skin. Although no recommendation can be made regarding which type of carriers can provide better skin penetration, the lipid-based colloidal systems appear to be favored due to their compatibility. In addition, the physical technologies provide unique advantages in delivering hydrophilic macromolecules for the skin immunization. As a new class of permeation enhancers, skin penetrating peptides are gaining more attention in drug delivery to skin cells. For the design of robust site-specific drug delivery systems, the impacts of diseased state and drug properties should not be disregarded.

KEYWORDS:

• Site-specific
• drug delivery
• skin disease
• nanoparticles
• microneedles
• prodrugs

Article highlights

• Enhancement of the site-specific drug delivery in the skin for improving the treatment of skin diseases and reducing the systemic side effect has been increasingly explored using methodologies including particle-based drug carriers, physical technologies, and chemical approaches.

• Particle-based carriers are of particular interest in the field of site-specific drug delivery in the skin, as they can be tailored with physicochemical properties and surface modification to allow for controlled drug release and skin targeting. Due to the good compatibility with the skin, the lipid-based colloidal systems appear to be more favored for dermal drug delivery.

• The physical enhancement technologies can be used where the limitation of other methodologies have been reached. They are usually applied in combination with particle-based drug carriers to improve the dermal delivery of small molecules and macromolecules, which also offers an exciting avenue for enhancement of skin immunization.

• The chemical approaches appear to be a simple alternative or auxiliary for the delivery of active agents. As a new class of permeation enhancers, the skin penetrating peptides are gaining more attention in drug delivery to the skin and its active cells.

• Quantitative analysis of drug distribution in the skin is the most challenging task for evaluation of the drug delivery systems. Novel technologies have been continuously explored, and they may be selected and used in combination according to the pharmacological action, sites of drug location, and complexity of the drug product.

• Safety issues, obscure delivering mechanisms, and difficulties for scale-up production are the major challenges that requires ongoing consideration in the development of site-specific skin drug delivery systems.

This box summarizes key points contained in the article.

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.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they have financial interest in microneedle technology for transdermal drug delivery, which is addressed in the manuscript. The conflict of interest is managed by Georgia Technology University. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (No. 81703435) and the Doctor Startup Science Foundation of Liaoning Province (NO. 20170520412).