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Critical Reviews™ in Therapeutic Drug Carrier Systems
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ISSN Print: 0743-4863
ISSN Online: 2162-660X

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Critical Reviews™ in Therapeutic Drug Carrier Systems

DOI: 10.1615/CritRevTherDrugCarrierSyst.v26.i6.20
pages 581-606

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

S. S. Lanke
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Mercer University, Atlanta, GA
J. G. Strom
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Mercer University, Atlanta, GA
Ajay K. Banga
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Mercer University, Atlanta, GA, USA

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.


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