Enhanced transdermal delivery of low molecular weight heparin by barrier perturbation

Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, 3001 Mercer University, Mercer University, Atlanta, GA 30341, United States.
International Journal of Pharmaceutics (Impact Factor: 3.65). 09/2008; 365(1-2):26-33. DOI: 10.1016/j.ijpharm.2008.08.028
Source: PubMed


The purpose of this work was to investigate the in vitro transdermal delivery of low molecular weight heparin (LMWH). Hairless rat skin was mounted on Franz diffusion cells and treated with various enhancement strategies. Passive flux was essentially zero and remained low even after iontophoresis (0.065 U cm(-2) h(-1)) or application of ultrasound (0.058 U cm(-2) h(-1)). A significant increase in flux across tape stripped skin (4.0 U cm(-2) h(-1)) suggests the interaction of stratum corneum (SC) with LMWH which was confirmed using Differential Scanning Calorimetry and Fourier Transform-Infrared spectrophotometry. Maltose microneedles were then employed as a means to locally disrupt and bypass the SC. Transepidermal water loss (TEWL) and transcutaneous electrical resistance (TER) were measured to confirm the barrier disruption. Microneedles breached the SC resulting in increased TEWL, decreased TER and enhanced LMWH permeability (0.175 U cm(-2) h(-1)). Microneedles when used in conjunction with iontophoresis had a synergistic effect on LMWH delivery resulting in enhancement of flux by 14.7-fold as compared to iontophoresis used alone. Confocal laser scanning microscopy substantiated the evidence about LMWH interaction with SC. In conclusion, LMWH was shown to interact with SC and therefore tape stripping or microneedles dramatically increased its delivery due to disruption of the SC skin barrier.

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    • "Clobetasol propionate is a corticosteroid used to treat various skin disorders including eczema and psoriasis (Shah et al. 2002; Weigmann et al. 1999). The transdermal delivery of low molecular weight heparin (LMWH) was investigated with skin tape stripping to estimate the enhancement strategies combined with micro-needle , ultrasound, or iontophoresis (Lanke et al. 2009). The flux of LMWH was significantly enhanced as compared with each self-supported method. "
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    Archives of Pharmacal Research 02/2014; 37(4). DOI:10.1007/s12272-014-0342-4 · 2.05 Impact Factor
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    • "It has recently been proposed that the combination of skin barrier impairment using MN coupled with iontophoresis (ITP) may allow rapid delivery of vaccines or hormones (e.g., insulin), as well as enabling delivery of conventional drug substances to be precisely controlled.17, 18 Ultimately, this may enable bolus, pulsatile or responsive drug administration. Combination of MN and ITP has shown to lead to a synergistic enhancement in transdermal delivery of a range of molecules.17–21 "
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    Advanced Functional Materials 12/2012; 22(23):4879-4890. DOI:10.1002/adfm.201200864 · 11.81 Impact Factor
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    • "LMWH is a polyanionic mucopolysaccharide composed of repeated disaccharide units of D-glucosamine and uronic acid linked by 1,4 interglycosidic bonds. The IR spectrum of LMWH showed bands of the main functional groups in the disaccharide units (Yang et al., 2006; Lanke et al., 2009 "
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