Radiofrequency-triggered release for on-demand delivery of therapeutics from titania nanotube drug-eluting implants.

AIM This study aimed to demonstrate radiofrequency (RF)-triggered release of drugs and drug carriers from drug-eluting implants using gold nanoparticles as energy transducers. MATERIALS & METHODS Titanium wire with a titania nanotube layer was used as an implant loaded with indomethacin and micelles (tocopheryl PEG succinate) as a drug and drug carrier model. RF signals were generated from a customized RF generator to trigger in vitro release. RESULTS & DISCUSSION Within 2.5 h, 18 mg (92%) of loaded drug and 14 mg (68%) of loaded drug carriers were released using short RF exposure (5 min), compared with 5 mg (31%) of drug and 2 mg (11%) of drug carriers without a RF trigger. Gold nanoparticles can effectively function as RF energy transducers inside titania nanotubes for rapid release of therapeutics at arbitrary times. CONCLUSION The results of this study show that RF is a promising strategy for triggered release from implantable drug delivery systems where on-demand delivery of therapeutics is required.

[1]  Krishna Kant,et al.  Tailoring the surface functionalities of titania nanotube arrays. , 2010, Biomaterials.

[2]  J. Addai-Mensah,et al.  A multi-drug delivery system with sequential release using titania nanotube arrays. , 2012, Chemical communications.

[3]  Carter Kittrell,et al.  Size-dependent joule heating of gold nanoparticles using capacitively coupled radiofrequency fields , 2009 .

[4]  Jonas Addai-Mensah,et al.  Magnetic-responsive delivery of drug-carriers using titania nanotube arrays , 2012 .

[5]  Andre G. Skirtach,et al.  Stimuli-sensitive nanotechnology for drug delivery , 2009 .

[6]  Robert Langer,et al.  Small-scale systems for in vivo drug delivery , 2003, Nature Biotechnology.

[7]  K. Hamad-Schifferli,et al.  Remote electronic control of DNA hybridization through inductive coupling to an attached metal nanocrystal antenna , 2002, Nature.

[8]  M Navarro,et al.  Biomaterials in orthopaedics , 2008, Journal of The Royal Society Interface.

[9]  J. Addai-Mensah,et al.  Polymer micelles for delayed release of therapeutics from drug-releasing surfaces with nanotubular structures. , 2012, Macromolecular bioscience.

[10]  S. Goldberg,et al.  Radiofrequency tumor ablation: principles and techniques. , 2001, European journal of ultrasound : official journal of the European Federation of Societies for Ultrasound in Medicine and Biology.

[11]  K. Gulati,et al.  Controlling Drug Release from Titania Nanotube Arrays Using Polymer Nanocarriers and Biopolymer Coating , 2011 .

[12]  Dusan Losic,et al.  Self-ordered nanopore and nanotube platforms for drug delivery applications , 2009, Expert opinion on drug delivery.

[13]  Andrei Ghicov,et al.  Self‐Ordering Electrochemistry: A Review on Growth and Functionality of TiO2 Nanotubes and Other Self‐Aligned MOx Structures , 2009 .

[14]  Youqing Shen,et al.  Fabrication of micellar nanoparticles for drug delivery through the self-assembly of block copolymers , 2010 .

[15]  H. Rack,et al.  Titanium alloys in total joint replacement--a materials science perspective. , 1998, Biomaterials.

[16]  G. Kwon,et al.  Nanotechnology in drug delivery , 2009 .

[17]  Robert Langer,et al.  Drugs on Target , 2001, Science.

[18]  Thomas Jay Webster,et al.  Nanomedicine for implants: a review of studies and necessary experimental tools. , 2007, Biomaterials.

[19]  B. Su,et al.  Titanium nanofeaturing for enhanced bioactivity of implanted orthopedic and dental devices. , 2013, Nanomedicine.

[20]  Steven A Curley,et al.  Radiofrequency ablation , 2004, Cancer.

[21]  Dusan Losic,et al.  Nanoengineered drug-releasing Ti wires as an alternative for local delivery of chemotherapeutics in the brain , 2012, International journal of nanomedicine.

[22]  Steven A Curley,et al.  Non-invasive radiofrequency ablation of malignancies mediated by quantum dots, gold nanoparticles and carbon nanotubes. , 2011, Therapeutic delivery.

[23]  Peter Pivonka,et al.  Characterization of drug-release kinetics in trabecular bone from titania nanotube implants , 2012, International journal of nanomedicine.

[24]  Yokoyama Masayuki,et al.  Block copolymer micelles as vehicles for drug delivery , 1993 .

[25]  Dusan Losic,et al.  Local drug delivery to the bone by drug-releasing implants: perspectives of nano-engineered titania nanotube arrays. , 2012, Therapeutic delivery.

[26]  David L. Wilson,et al.  Noninvasive monitoring of local drug release in a rabbit radiofrequency (RF) ablation model using X-ray computed tomography. , 2002, Journal of controlled release : official journal of the Controlled Release Society.

[27]  Catherine J. Murphy,et al.  Seeding Growth for Size Control of 5−40 nm Diameter Gold Nanoparticles , 2001 .

[28]  Jorge I. Rodriguez-Devora,et al.  Physically facilitating drug-delivery systems. , 2012, Therapeutic delivery.

[29]  Sweta Modi,et al.  Role of polyanhydrides as localized drug carriers. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[30]  T. Desai,et al.  Microfabricated drug delivery systems: from particles to pores. , 2003, Advanced drug delivery reviews.

[31]  M. Zilberman,et al.  Antibiotic-eluting medical devices for various applications. , 2008, Journal of controlled release : official journal of the Controlled Release Society.

[32]  Tejal A Desai,et al.  Decreased Staphylococcus epidermis adhesion and increased osteoblast functionality on antibiotic-loaded titania nanotubes. , 2007, Biomaterials.

[33]  V. Torchilin,et al.  Targeted polymeric micelles for delivery of poorly soluble drugs , 2004, Cellular and Molecular Life Sciences CMLS.

[34]  Patrik Schmuki,et al.  TiO2 nanotubes: synthesis and applications. , 2011, Angewandte Chemie.

[35]  D. Jain,et al.  Implantable Drug Delivery System: A Review , 2012 .

[36]  Tejal A Desai,et al.  Influence of engineered titania nanotubular surfaces on bone cells. , 2007, Biomaterials.

[37]  Dusan Losic,et al.  Ultrasound enhanced release of therapeutics from drug-releasing implants based on titania nanotube arrays. , 2013, International journal of pharmaceutics.

[38]  Aldo R Boccaccini,et al.  A review of the biological response to ionic dissolution products from bioactive glasses and glass-ceramics. , 2011, Biomaterials.

[39]  Dusan Losic,et al.  Drug-eluting Ti wires with titania nanotube arrays for bone fixation and reduced bone infection , 2011, Nanoscale research letters.

[40]  B. Sumerlin,et al.  Biological‐ and Field‐Responsive Polymers: Expanding Potential in Smart Materials , 2011 .

[41]  S. Krishnan,et al.  Nanoparticle-mediated hyperthermia in cancer therapy. , 2011, Therapeutic delivery.

[42]  M. Vallet‐Regí,et al.  Recent advances in ceramic implants as drug delivery systems for biomedical applications , 2008, International journal of nanomedicine.

[43]  Marek W. Urban,et al.  Handbook of Stimuli-Responsive Materials , 2015 .

[44]  J. Addai-Mensah,et al.  Polymeric micelles in porous and nanotubular implants as a new system for extended delivery of poorly soluble drugs , 2011 .

[45]  G. Lewis Alternative acrylic bone cement formulations for cemented arthroplasties: present status, key issues, and future prospects. , 2008, Journal of biomedical materials research. Part B, Applied biomaterials.

[46]  Dusan Losic,et al.  Biocompatible polymer coating of titania nanotube arrays for improved drug elution and osteoblast adhesion. , 2012, Acta biomaterialia.

[47]  Rubiana M Mainardes,et al.  Drug delivery systems: past, present, and future. , 2004, Current drug targets.

[48]  M. Lindén,et al.  Sol-gel synthesis of a multifunctional, hierarchically porous silica/apatite composite. , 2005, Biomaterials.

[49]  Emeka Nkenke,et al.  In vivo evaluation of anodic TiO2 nanotubes: an experimental study in the pig. , 2009, Journal of biomedical materials research. Part B, Applied biomaterials.

[50]  D. Losic,et al.  A simple approach for synthesis of TiO2 nanotubes with through‐hole morphology , 2009 .

[51]  Tejal A Desai,et al.  Titania nanotubes: a novel platform for drug-eluting coatings for medical implants? , 2007, Small.