Indirect rapid prototyping of antibacterial acid anhydride copolymer microneedles

Microneedles are needle-like projections with microscale features that may be used for transdermal delivery of a variety of pharmacologic agents, including antibacterial agents. In the study described in this paper, an indirect rapid prototyping approach involving a combination of visible light dynamic mask micro-stereolithography and micromolding was used to prepare microneedle arrays out of a biodegradable acid anhydride copolymer, Gantrez(®) AN 169 BF. Fourier transform infrared spectroscopy, energy dispersive x-ray spectrometry and nanoindentation studies were performed to evaluate the chemical and mechanical properties of the Gantrez(®) AN 169 BF material. Agar plating studies were used to evaluate the in vitro antimicrobial performance of these arrays against Bacillus subtilis, Candida albicans, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. Large zones of growth inhibition were noted for Escherichia coli, S. aureus, Enterococcus faecalis and B. subtilis. The performance of Gantrez(®) AN 169 BF against several bacteria suggests that biodegradable acid anhydride copolymer microneedle arrays prepared using visible light dynamic mask micro-stereolithography micromolding may be useful for treating a variety of skin infections.

[1]  L. Gang,et al.  The properties of demoulding of Ni and Ni-PTFE moulding inserts , 2005 .

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

[3]  Aleksandr Ovsianikov,et al.  Two-photon polymerization of microneedles for transdermal drug delivery , 2010, Expert opinion on drug delivery.

[4]  Holger Becker,et al.  Hot embossing as a method for the fabrication of polymer high aspect ratio structures , 2000 .

[5]  Yannic B Schuetz,et al.  Emerging strategies for the transdermal delivery of peptide and protein drugs , 2005, Expert opinion on drug delivery.

[6]  Yangchao Tian,et al.  Study of Hot Embossing Using Nickel and Ni–PTFE LIGA Mold Inserts , 2007, Journal of Microelectromechanical Systems.

[7]  Roger Narayan,et al.  Microneedle array-based carbon paste amperometric sensors and biosensors. , 2011, The Analyst.

[8]  B. Chichkov,et al.  Pulsed laser deposition of antimicrobial silver coating on Ormocer® microneedles , 2009, Biofabrication.

[9]  Aleksandr Ovsianikov,et al.  Two Photon Polymerization‐Micromolding of Polyethylene Glycol‐Gentamicin Sulfate Microneedles , 2010, Advanced engineering materials.

[10]  Ronen Polsky,et al.  Integrated carbon fiber electrodes within hollow polymer microneedles for transdermal electrochemical sensing. , 2011, Biomicrofluidics.

[11]  N. Heskel.  Allergic contact dermatitis from stomadhesive paste , 1987, Contact dermatitis.

[12]  A. Ludwig,et al.  Microneedles for transdermal drug delivery: a minireview. , 2008, Frontiers in bioscience : a journal and virtual library.

[13]  Mark R Prausnitz,et al.  Microneedles for transdermal drug delivery. , 2004, Advanced drug delivery reviews.

[14]  R. Narayan,et al.  Modification of microneedles using inkjet printing. , 2011, AIP advances.

[15]  Jung-Hwan Park,et al.  Biodegradable polymer microneedles: fabrication, mechanics and transdermal drug delivery. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[16]  G. Pharr,et al.  An improved technique for determining hardness and elastic modulus using load and displacement sensing indentation experiments , 1992 .

[17]  Jung-Hwan Park,et al.  Analysis of Mechanical Failure of Polymer Microneedles by Axial Force. , 2010, The journal of the Korean Physical Society.

[18]  S. Mitragotri,et al.  Current status and future potential of transdermal drug delivery , 2004, Nature Reviews Drug Discovery.

[19]  Kunwoo Lee,et al.  The development of a CAD environment to determine the preferred build-up direction for layered manufacturing , 1998 .

[20]  N. Stone,et al.  Peristomal allergic contact dermatitis – case report and review of the literature , 2005, Contact dermatitis.

[21]  J. Veciana,et al.  High Loading of Gentamicin in Bioadhesive PVM/MA Nanostructured Microparticles Using Compressed Carbon-Dioxide , 2011, Pharmaceutical Research.

[22]  Anthony Morrissey,et al.  Cutaneous DNA delivery and gene expression in ex vivo human skin explants via wet-etch microfabricated microneedles , 2005, Journal of drug targeting.

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

[24]  Seok-Hee Lee,et al.  Cross-section segmentation for improving the shape accuracy of microstructure array in projection microstereolithography , 2010 .

[25]  Adnan Nasir,et al.  Deposition of antimicrobial coatings on microstereolithography-fabricated microneedles , 2011 .

[26]  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.

[27]  J. Fowler,et al.  Peristomal allergic contact dermatitis due to Gantrez in Stomahesive paste. , 2000, Journal of the American Academy of Dermatology.

[28]  Ryan F. Donnelly,et al.  Design, Optimization and Characterisation of Polymeric Microneedle Arrays Prepared by a Novel Laser-Based Micromoulding Technique , 2010, Pharmaceutical Research.

[29]  W. McKeehan,et al.  POLYMERIC PHARMACEUTICAL COATING MATERIALS. I. PREPARATION AND PROPERTIES. , 1965, Journal of pharmaceutical sciences.

[30]  J. Irache,et al.  Bioadhesive Properties of Gantrez Nanoparticles , 2005, Molecules.

[31]  Lee Yong Tsui,et al.  A study of the staircase effect induced by material shrinkage in rapid prototyping , 2005 .

[32]  Desmond I. J. Morrow,et al.  Microneedle-mediated intradermal nanoparticle delivery: Potential for enhanced local administration of hydrophobic pre-formed photosensitisers. , 2010, Photodiagnosis and photodynamic therapy.