Enhanced transdermal delivery of low molecular weight heparin by barrier perturbation
ABSTRACT 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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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 · 1.75 Impact Factor
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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 · 1.88 Impact Factor
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ABSTRACT: Purpose: Kojic dipalmitate (KDP), dissolved in oil medium, have been tested for their capability to permeate through artificial skin using Franz cells. Methods: It has been discovered that there was no significant variation in terms of drug release between nano-creams and normal creams at P-value > 0.05. KDP, incorporated into normal and nano-creams, was applied into the skin of a male Wistar rat. The storage behavior of KDP, loaded in nano-creams (diameter < 350 nm) and applied to the hair follicles was investigated. The results were compared with the findings obtained by using the same amount of KDP in normal cream. Tape stripping technique was used to investigate the storage behavior of both formulations in hair follicles and then quantifying KDP by means of HPLC method. Results: It was observed that the KDP loaded into nano-creams was trapped in the hair follicles for more than 7 d, while KDP loaded into normal creams was trapped for less than 3 d i.e. a faster depletion rate. The movement of the hair might act as a pumping mechanism that pushes the nanoparticles deeply into the hair follicles. Conclusion: The result from this study can be applied for the development of KDP for topical use.Asian Journal of Pharmaceutical Sciences 03/2010; 5(6):251-265.