Remotely triggered release of small molecules from LaB6@SiO2-loaded polycaprolactone microneedles.

We established near-infrared (NIR)-light-triggered transdermal delivery systems by encapsulating NIR absorbers, silica-coated lanthanum hexaboride (LaB6@SiO2) nanostructures and the cargo molecule to be released in biodegradable polycaprolactone (PCL) microneedles. Acting as a local heat source when exposed to an NIR laser, these nanostructures cause a phase transition of the microneedles, thereby increasing the mobility of the polymer chains and triggering drug release from the microneedles. On IR thermal images, the light-triggered melting behavior of the LaB6@SiO2-loaded microneedles was observed. By adjusting the irradiation time and the laser on/off cycles, the amount of molecules released was controlled accurately. Drug release was switched on and off for at least three cycles, and a consistent dose was delivered in each cycle with high reproducibility. The designed microneedles were remotely triggered by laser irradiation for the controlled release of a chemotherapeutic drug, doxorubicin hydrochloride, in vivo. This system would enable dosages to be adjusted accurately to achieve a desired effect, feature a low off-state drug leakage to minimize basal effects and can increase the flexibility of pharmacotherapy performed to treat various medical conditions.

[1]  Samantha A. Meenach,et al.  Synthesis and characterization of CREKA-conjugated iron oxide nanoparticles for hyperthermia applications. , 2014, Acta biomaterialia.

[2]  Jayakumar Rajadas,et al.  Polyvinylpyrrolidone microneedles enable delivery of intact proteins for diagnostic and therapeutic applications. , 2013, Acta biomaterialia.

[3]  Shih-Fang Huang,et al.  Fully embeddable chitosan microneedles as a sustained release depot for intradermal vaccination. , 2013, Biomaterials.

[4]  Dong-Hwang Chen,et al.  Preparation of LaB6 nanoparticles as a novel and effective near-infrared photothermal conversion material , 2012 .

[5]  Wolfgang J Parak,et al.  NIR-light triggered delivery of macromolecules into the cytosol. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[6]  B. Mazzolai,et al.  Gold nanoshell/polysaccharide nanofilm for controlled laser-assisted tissue thermal ablation. , 2014, ACS nano.

[7]  Zhuang Liu,et al.  Gold nanorod-cored biodegradable micelles as a robust and remotely controllable doxorubicin release system for potent inhibition of drug-sensitive and -resistant cancer cells. , 2013, Biomacromolecules.

[8]  L. Brannon-Peppas,et al.  Nanoparticle and targeted systems for cancer therapy. , 2004, Advanced drug delivery reviews.

[9]  Jung-Hwan Park,et al.  Dissolving microneedles for transdermal drug delivery. , 2008, Biomaterials.

[10]  R. Srivastava,et al.  pH- and thermosensitive thin lipid layer coated mesoporous magnetic nanoassemblies as a dual drug delivery system towards thermochemotherapy of cancer. , 2014, Acta biomaterialia.

[11]  B. Lai,et al.  LaB6 nanoparticles with carbon-doped silica coating for fluorescence imaging and near-IR photothermal therapy of cancer cells. , 2013, Acta biomaterialia.

[12]  Y. Demir,et al.  Characterization of Polymeric Microneedle Arrays for Transdermal Drug Delivery , 2013, PloS one.

[13]  D. Morton,et al.  Normal tissue and solid tumor effects of hyperthermia in animal models and clinical trials. , 1979, Cancer research.

[14]  J. Burdick,et al.  Light-sensitive polypeptide hydrogel and nanorod composites. , 2010, Small.

[15]  Adah Almutairi,et al.  Low power, biologically benign NIR light triggers polymer disassembly. , 2011, Macromolecules.

[16]  Robert Langer,et al.  Near-infrared–actuated devices for remotely controlled drug delivery , 2014, Proceedings of the National Academy of Sciences.

[17]  Junjie Liu,et al.  Hydrazone-bearing PMMA-functionalized magnetic nanocubes as pH-responsive drug carriers for remotely targeted cancer therapy in vitro and in vivo. , 2014, ACS applied materials & interfaces.

[18]  C. Song Effect of local hyperthermia on blood flow and microenvironment: a review. , 1984, Cancer research.

[19]  C. Burda,et al.  Near infrared light-triggered drug generation and release from gold nanoparticle carriers for photodynamic therapy. , 2014, Small.

[20]  Mark R Prausnitz,et al.  Dissolving microneedle patch for transdermal delivery of human growth hormone. , 2011, Small.

[21]  E. Y. K. Ng,et al.  Prediction and parametric analysis of thermal profiles within heated human skin using the boundary element method , 2010, Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences.

[22]  A. Raichur,et al.  Polyelectrolyte/silver nanocomposite multilayer films as multifunctional thin film platforms for remote activated protein and drug delivery. , 2013, Acta biomaterialia.

[23]  Shi-zhong Luo,et al.  Dual pH-triggered multistage drug delivery systems based on host-guest interaction-associated polymeric nanogels. , 2014, Chemical communications.

[24]  Ronald A Siegel,et al.  Stimuli sensitive polymers and self regulated drug delivery systems: a very partial review. , 2014, Journal of controlled release : official journal of the Controlled Release Society.

[25]  Mei-Chin Chen,et al.  Chitosan microneedle patches for sustained transdermal delivery of macromolecules. , 2012, Biomacromolecules.

[26]  Ryan F. Donnelly,et al.  Design and physicochemical characterisation of novel dissolving polymeric microneedle arrays for transdermal delivery of high dose, low molecular weight drugs , 2014, Journal of controlled release : official journal of the Controlled Release Society.

[27]  Jin Chang,et al.  pH- and reduction-responsive polymeric lipid vesicles for enhanced tumor cellular internalization and triggered drug release. , 2014, ACS applied materials & interfaces.

[28]  Robert Langer,et al.  A magnetically triggered composite membrane for on-demand drug delivery. , 2009, Nano letters.

[29]  Brian P. Timko,et al.  Remotely Triggerable Drug Delivery Systems , 2010, Advanced materials.

[30]  Dong-Hwang Chen,et al.  Vancomycin-modified LaB6@SiO2/Fe3O4 composite nanoparticles for near-infrared photothermal ablation of bacteria. , 2013, Acta biomaterialia.

[31]  R. Weissleder A clearer vision for in vivo imaging , 2001, Nature Biotechnology.

[32]  Mei-Chin Chen,et al.  Dissolving polymer microneedle patches for rapid and efficient transdermal delivery of insulin to diabetic rats. , 2013, Acta biomaterialia.