Enhancement of Transdermal Delivery of Heparin by Various Physical and Chemical Enhancement Techniques

Abstract

Conventional anticoagulants such as unfractionated heparin and warfarin have numerous limitations compared with low-molecular-weight heparin (LMWH). However, the need for repetitive parenteral administration is still a major disadvantage of LMWH, and the absorption of macromolecules such as LMWH across the gastrointestinal tract is very poor. Due to these problems with oral delivery of LMWH, transdermal delivery can be considered as an alternate route of administration. However, overcoming the skin barrier is necessary for the transport of larger molecules across the stratum corneum. This review focuses on the transdermal delivery of LMWH, providing a brief overview of heparin delivery via invasive and oral routes and discusses the advantages of using LMWH rather than heparin for transdermal delivery, and the primary reasons for poor permeability of LMWH. Various strategies employed for transdermal delivery of heparin are summarized, and chemical and physical enhancement techniques or suitable formulations that can be used to improve transcutaneous penetration and various chemical enhancers that act on the skin by different modes of action are discussed. We also consider physical approaches such as iontophoresis, electroporation, and ultrasound, as well as combination strategies to deliver heparin. The developments in physical and chemical enhancement strategies over the past decade are summarized. In addition, recent novel approaches such as microneedles employed for the transdermal delivery of LMWH are also discussed.

Pharmacology of Heparin and Related Drugs

“…Others have developed transdermal approaches to deliver heparin (Lanke et al, 2009), and there have also been various attempts to develop inhaled formulations of heparin. Thus, as discussed above, heparin has been administered safely to humans by inhalation for up to 28 days (Markart et al, 2010), and in most studies in patients, inhaled delivery of heparin is not associated with adverse effects and indeed does not cause systemic changes in coagulation (Shastri et al, 2014).…”

Pharmacology of Heparin and Related Drugs: An Update

“…Others have developed transdermal approaches to deliver heparin (Lanke et al, 2009) as an alternative method to parenteral administration for anticoagulant use.…”

Microneedles for drug delivery: trends and progress

“…The amount of drug that is delivered can also be increased. However, an understanding of the permeability of skin would need to be established in order to determine how to increase drug content (Lanke et al, 2009;Prausnitz et al, 2009;Subedi et al, 2010). It is important to look at skin thickness when investigating increasing permeability of skin, as increasing skin permeability is important for TDD.…”