Formation and Closure of Microchannels in Skin Following Microporation

ABSTRACTPurposeTo characterize the microchannels created in hairless rat skin by microneedles and investigate their closure following exposure to different occlusive conditions.MethodsMaltose microneedles were characterized by scanning electron microscopy. The microchannels created and their closure when exposed to different conditions was investigated using a variety of techniques.ResultsMicroscopic imaging indicates a pyramidal geometry of maltose microneedles with an average length of 559 ± 14 μm and tip radius of 4 μm. Upon insertion into skin, they created microchannels with an average surface diameter of 60 μm and an average depth of 160 ± 20 μm as observed by histological sectioning and confocal microscopy. Skin recovers its barrier function within 3–4 hrs, and microchannels closed within 15 hrs of poration when exposed to environment. However, when occluded, the microchannels remained open for up to 72 hrs in vivo, as observed by calcein imaging, transepidermal water loss measurements and methylene blue staining.ConclusionMaltose microneedles penetrated the stratum corneum barrier and created microchannels in skin which completely close within 15 hrs after poration. However, under occluded conditions, barrier recovery can be delayed for up to 72 hrs in vivo.

[1]  V. Rogiers,et al.  Sustained serine proteases activity by prolonged increase in pH leads to degradation of lipid processing enzymes and profound alterations of barrier function and stratum corneum integrity. , 2005, The Journal of investigative dermatology.

[2]  P. Elias,et al.  Lamellar body secretory response to barrier disruption. , 1992, The Journal of investigative dermatology.

[3]  Chandra Sekhar Kolli,et al.  Characterization of Solid Maltose Microneedles and their Use for Transdermal Delivery , 2007, Pharmaceutical Research.

[4]  E. Choi,et al.  Functional and structural changes of the epidermal barrier induced by various types of insults in hairless mice , 2001, Archives of Dermatological Research.

[5]  M. Cormier,et al.  Transdermal Delivery of Antisense Oligonucleotides with Microprojection Patch (macroflux®) Technology , 2001, Pharmaceutical Research.

[6]  Jung-Hwan Park,et al.  Biodegradable polymer microneedles: fabrication, mechanics and transdermal drug delivery , 2004, The 26th Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[7]  M. Taljebini,et al.  Cutaneous permeability barrier repair following various types of insults: kinetics and effects of occlusion. , 1996, Skin pharmacology : the official journal of the Skin Pharmacology Society.

[8]  A. Morrissey,et al.  Clinical administration of microneedles: skin puncture, pain and sensation , 2009, Biomedical microdevices.

[9]  M. Cormier,et al.  Effect of delivery parameters on immunization to ovalbumin following intracutaneous administration by a coated microneedle array patch system. , 2006, Vaccine.

[10]  P. Elias,et al.  Functional consequences of a neutral pH in neonatal rat stratum corneum. , 2004, The Journal of investigative dermatology.

[11]  Mark G. Allen,et al.  Hollow metal microneedles for insulin delivery to diabetic rats , 2005, IEEE Transactions on Biomedical Engineering.

[12]  Wijaya Martanto,et al.  Transdermal Delivery of Insulin Using Microneedles in Vivo , 2004, Pharmaceutical Research.

[13]  D. Barrow,et al.  Microfabricated silicon microneedles for nonviral cutaneous gene delivery , 2004, The British journal of dermatology.

[14]  P. Elias,et al.  Calcium and potassium inhibit barrier recovery after disruption, independent of the type of insult in hairless mice , 1997, Experimental dermatology.

[15]  Jyoti Gupta MICRONEEDLES FOR TRANSDERMAL DRUG DELIVERY IN HUMAN SUBJECTS , 2009 .

[16]  P. Elias,et al.  Integrity of the permeability barrier is crucial for maintenance of the epidermal calcium gradient , 1994, The British journal of dermatology.

[17]  A. Banga Microporation applications for enhancing drug delivery. , 2009, Expert opinion on drug delivery.

[18]  Mahmoud Ameri,et al.  Transdermal delivery of desmopressin using a coated microneedle array patch system. , 2004, Journal of controlled release : official journal of the Controlled Release Society.

[19]  P. Elias,et al.  Ionic calcium reservoirs in mammalian epidermis: ultrastructural localization by ion-capture cytochemistry. , 1985, The Journal of investigative dermatology.

[20]  Mark R Prausnitz,et al.  Precise microinjection into skin using hollow microneedles. , 2006, The Journal of investigative dermatology.

[21]  D. Das,et al.  Optimizing microneedle arrays for transdermal drug delivery: Extension to non-square distribution of microneedles , 2009, Journal of drug targeting.

[22]  Mark G. Allen,et al.  Microfabricated needles for transdermal delivery of macromolecules and nanoparticles: Fabrication methods and transport studies , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[23]  P. Elias,et al.  Calcium and potassium are important regulators of barrier homeostasis in murine epidermis. , 1992, The Journal of clinical investigation.

[24]  L. Kennish,et al.  A review of the effect of occlusive dressings on lamellar bodies in the stratum corneum and relevance to transdermal absorption. , 2005, Dermatology online journal.

[25]  A. Banga,et al.  In vitro transdermal delivery of therapeutic antibodies using maltose microneedles. , 2009, International journal of pharmaceutics.

[26]  J. Matriano,et al.  Macroflux® Microprojection Array Patch Technology: A New and Efficient Approach for Intracutaneous Immunization , 2004, Pharmaceutical Research.

[27]  Manhee Han,et al.  Influence of the delivery systems using a microneedle array on the permeation of a hydrophilic molecule, calcein. , 2008, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[28]  Melissa Ai Ling Teo,et al.  In Vitro and In Vivo Characterization of MEMS Microneedles , 2005, Biomedical microdevices.

[29]  C. Shearwood,et al.  Transdermal microneedles for drug delivery applications , 2006 .

[30]  P. Elias,et al.  Epidermal lipids, barrier function, and desquamation. , 1983, The Journal of investigative dermatology.

[31]  H. Kalluri,et al.  Microneedles and transdermal drug delivery , 2009 .

[32]  Diganta Bhusan Das,et al.  Optimizing Microneedle Arrays to Increase Skin Permeability for Transdermal Drug Delivery , 2009, Annals of the New York Academy of Sciences.

[33]  Kenneth R Feingold,et al.  pH directly regulates epidermal permeability barrier homeostasis, and stratum corneum integrity/cohesion. , 2003, The Journal of investigative dermatology.

[34]  Mark R Prausnitz,et al.  Kinetics of skin resealing after insertion of microneedles in human subjects. , 2011, Journal of controlled release : official journal of the Controlled Release Society.

[35]  P. Elias,et al.  A role for ions in barrier recovery after acute perturbation. , 1994, The Journal of investigative dermatology.

[36]  P. Elias,et al.  Transepidermal water loss: the signal for recovery of barrier structure and function. , 1989, Journal of lipid research.

[37]  S. H. Lee,et al.  The morphologic changes in lamellar bodies and intercorneocyte lipids after tape stripping and occlusion with a water vapor-impermeable membrane , 1998, Archives of Dermatological Research.

[38]  Diane E. Sutter,et al.  Improved genetic immunization via micromechanical disruption of skin-barrier function and targeted epidermal delivery , 2002, Nature Medicine.