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.
"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. "
[Show abstract][Hide abstract] ABSTRACT: Recently a variety of polymeric vehicles, such as micelles, nanoparticles, and polymersomes, have been explored and some of them are clinically used to deliver therapeutic drugs through skin. In topical delivery, the polymeric vehicles as drug carrier should guarantee non-toxicity, long-term stability, and permeation efficacy for drugs, etc. For the development of the successful topical delivery system, it is of importance to develop the polymeric vehicles of well-defined intrinsic properties, such as molecular weights, HLB, chemical composition, topology, specific ligand conjugation and to investigate the effects of the properties on drug permeation behavior. In addition, the role of polymeric vehicles must be elucidated in in vitro and in vivo analyses. This article describes some important features of polymeric vehicles and corresponding analytical methods in topical delivery even though the application span of polymers has been truly broad in the pharmaceutical fields.
Archives of Pharmacal Research 02/2014; 37(4). DOI:10.1007/s12272-014-0342-4 · 2.05 Impact Factor
"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 "
[Show abstract][Hide abstract] ABSTRACT: Unique microneedle arrays prepared from crosslinked polymers, which contain no drug themselves, are described. They rapidly take up skin interstitial fluid upon skin insertion to form continuous, unblockable, hydrogel conduits from attached patch-type drug reservoirs to the dermal microcirculation. Importantly, such microneedles, which can be fabricated in a wide range of patch sizes and microneedle geometries, can be easily sterilized, resist hole closure while in place, and are removed completely intact from the skin. Delivery of macromolecules is no longer limited to what can be loaded into the microneedles themselves and transdermal drug delivery is now controlled by the crosslink density of the hydrogel system rather than the stratum corneum, while electrically modulated delivery is also a unique feature. This technology has the potential to overcome the limitations of conventional microneedle designs and greatly increase the range of the type of drug that is deliverable transdermally, with ensuing benefits for industry, healthcare providers and, ultimately, patients.
"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 "
[Show abstract][Hide abstract] ABSTRACT: Biodegradable poly(lactic-co-glycolic acid) (PLGA) microspheres for the sustained release of low molecular weight heparin (LMWH) were prepared by a soild-in-oil-in-water (s/o/w) emulsion method. Prior to encapsulation, the LMWH micro-particles were fabricated by a modified freezing-induced phase separation method. The micro-particles were subsequently encapsulated into PLGA microspheres. Process optimization revealed that the NaCl concentration in the outer phase of s/o/w emulsion played a critical role in determining the properties of the microspheres. When the NaCl concentration increased from 0% to 5%, the encapsulation efficiency significantly increased from 51.5% to 76.8%. The initial burst release also decreased from 37.3% to 12.4%. In vitro release tests showed that LMWH released from PLGA microspheres in a sustained manner for about 14 days. Single injection of LMWH-loaded PLGA microspheres into rabbits resulted in an elevation of an anti-factor Xa activity for about 6 days. Furthermore, the integrity of the encapsulated LMWH was preserved during encapsulation process.
Journal of Microencapsulation 12/2011; 28(8):763-70. DOI:10.3109/02652048.2011.629740 · 1.59 Impact Factor
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