Low-frequency sonophoresis: application to the transdermal delivery of macromolecules and hydrophilic drugs.
BACKGROUND
Transdermal delivery of macromolecules provides an attractive alternative route of drug administration when compared to oral delivery and hypodermic injection because of its ability to bypass the harsh gastrointestinal tract and deliver therapeutics non-invasively. However, the barrier properties of the skin only allow small, hydrophobic permeants to traverse the skin passively, greatly limiting the number of molecules that can be delivered via this route. The use of low-frequency ultrasound for the transdermal delivery of drugs, referred to as low-frequency sonophoresis (LFS), has been shown to increase skin permeability to a wide range of therapeutic compounds, including both hydrophilic molecules and macromolecules. Recent research has demonstrated the feasibility of delivering proteins, hormones, vaccines, liposomes and other nanoparticles through LFS-treated skin. In vivo studies have also established that LFS can act as a physical immunization adjuvant. LFS technology is already clinically available for use with topical anesthetics, with other technologies currently under investigation.


METHODS
This review provides an overview of mechanisms associated with LFS-mediated transdermal delivery, followed by an in-depth discussion of the current applications of LFS technology for the delivery of hydrophilic drugs and macromolecules, including its use in clinical applications.


RESULTS
The reader will gain an insight into the field of LFS-mediated transdermal drug delivery, including how the use of this technology can improve on more traditional drug delivery methods.


CONCLUSIONS
Ultrasound technology has the potential to impact many more transdermal delivery platforms in the future due to its unique ability to enhance skin permeability in a controlled manner.
Massachusetts Institute of Technology, Department of Chemical Engineering, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Baris E
BE
Polat
Daniel
D
Blankschtein
Robert
R
Langer
D000279:Administration, Cutaneous; D001692:Biological Transport / Q000502:physiology; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D046911:Macromolecular Substances / Q000008:administration & dosage* / Q000737:chemistry; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry; D015612:Phonophoresis; D012869:Skin Absorption / Q000502:physiology*
D046911:Macromolecular Substances; D004364:Pharmaceutical Preparations