Polymeric microneedles for controlled transdermal drug delivery.

Polymeric microneedle (MN) systems are interesting transdermal drug delivery systems because of their controlled drug delivery, tunable properties, and ease of patient self-administration. They are biocompatible and can easily and painlessly penetrate the stratum corneum, delivering their contents into the dermis where they can be adsorbed into systemic circulation. Polymeric MNs can facilitate appropriate therapeutic dosing by controlling the release kinetics of pre-loaded drugs, targeting specific tissues, or responding to changing physiological conditions. This can be accomplished by modifying the degradation and swelling profiles of the host polymer and the diffusion profiles of the encapsulated drugs. In this review various mechanisms of controlled drug delivery using polymeric MNs, including new strategies, applications, and their future outlook are summarized and evaluated.

[1]  Zhen Gu,et al.  Microneedle-array patches loaded with hypoxia-sensitive vesicles provide fast glucose-responsive insulin delivery , 2015, Proceedings of the National Academy of Sciences.

[2]  Mei-Chin Chen,et al.  Near-Infrared Light-Activatable Microneedle System for Treating Superficial Tumors by Combination of Chemotherapy and Photothermal Therapy. , 2016, ACS nano.

[3]  Shichang Zhao,et al.  Composite-dissolving microneedle patches for chemotherapy and photothermal therapy in superficial tumor treatment. , 2018, Biomaterials science.

[4]  Akira Matsumoto,et al.  Microneedle‐Array Patch Fabricated with Enzyme‐Free Polymeric Components Capable of On‐Demand Insulin Delivery , 2018, Advanced Functional Materials.

[5]  Mark R Prausnitz,et al.  Microneedle patches: usability and acceptability for self-vaccination against influenza. , 2014, Vaccine.

[6]  Luca De Stefano,et al.  A Photolithographic Approach to Polymeric Microneedles Array Fabrication , 2015, Materials.

[7]  Ji Hoon Jeong,et al.  Smart vaccine delivery based on microneedle arrays decorated with ultra-pH-responsive copolymers for cancer immunotherapy. , 2018, Biomaterials.

[8]  D. Irvine,et al.  Releasable layer-by-layer assembly of stabilized lipid nanocapsules on microneedles for enhanced transcutaneous vaccine delivery. , 2012, ACS nano.

[9]  Ryan F Donnelly,et al.  Effects of microneedle length, density, insertion time and multiple applications on human skin barrier function: assessments by transepidermal water loss. , 2010, Toxicology in vitro : an international journal published in association with BIBRA.

[10]  Yukako Ito,et al.  Self-dissolving micropile array chip as percutaneous delivery system of protein drug. , 2010, Biological & pharmaceutical bulletin.

[11]  Jayanth Panyam,et al.  Biodegradable nanoparticles for drug and gene delivery to cells and tissue. , 2003, Advanced drug delivery reviews.

[12]  M. M. Pandey,et al.  Microneedles: A smart approach and increasing potential for transdermal drug delivery system. , 2019, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[13]  Zhen Gu,et al.  Bioresponsive Microneedles with a Sheath Structure for H2 O2 and pH Cascade-Triggered Insulin Delivery. , 2018, Small.

[14]  Ichiro Katayama,et al.  Clinical study and stability assessment of a novel transcutaneous influenza vaccination using a dissolving microneedle patch. , 2015, Biomaterials.

[15]  Mark R. Prausnitz,et al.  Stable incorporation of GM-CSF into dissolvable microneedle patch improves skin vaccination against influenza , 2018, Journal of controlled release : official journal of the Controlled Release Society.

[16]  Jeffrey M Karp,et al.  A self‐adherent, bullet‐shaped microneedle patch for controlled transdermal delivery of insulin , 2017, Journal of controlled release : official journal of the Controlled Release Society.

[17]  P. Maiti,et al.  Controlled drug delivery vehicles for cancer treatment and their performance , 2018, Signal Transduction and Targeted Therapy.

[18]  Mengyao Qin,et al.  Intradermal delivery of STAT3 siRNA to treat melanoma via dissolving microneedles , 2018, Scientific Reports.

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

[20]  Hyungil Jung,et al.  Droplet-born air blowing: novel dissolving microneedle fabrication. , 2013, Journal of controlled release : official journal of the Controlled Release Society.

[21]  Zhen Gu,et al.  Bioresponsive transcutaneous patches. , 2017, Current opinion in biotechnology.

[22]  Yu Chong,et al.  The mechanical properties of the skin epidermis in relation to targeted gene and drug delivery. , 2007, Biomaterials.

[23]  Maelíosa T. C. McCrudden,et al.  Potential of microneedles in enhancing delivery of photosensitising agents for photodynamic therapy. , 2014, Photodiagnosis and photodynamic therapy.

[24]  Niclas Roxhed,et al.  Wearable All-Solid-State Potentiometric Microneedle Patch for Intradermal Potassium Detection. , 2018, Analytical chemistry.

[25]  Lian-Hua Fu,et al.  Catalytic chemistry of glucose oxidase in cancer diagnosis and treatment. , 2018, Chemical Society reviews.

[26]  M. Prausnitz,et al.  Dihydroergotamine mesylate‐loaded dissolving microneedle patch made of polyvinylpyrrolidone for management of acute migraine therapy , 2017, Journal of controlled release : official journal of the Controlled Release Society.

[27]  Robert Langer,et al.  Transdermal drug delivery , 2008, Nature Biotechnology.

[28]  S. Nakagawa,et al.  Vaccine efficacy of transcutaneous immunization with amyloid β using a dissolving microneedle array in a mouse model of Alzheimer's disease , 2014, Journal of Neuroimmunology.

[29]  Eneko Larrañeta,et al.  Transdermal delivery of vitamin K using dissolving microneedles for the prevention of vitamin K deficiency bleeding , 2018, International journal of pharmaceutics.

[30]  Mei-Chin Chen,et al.  Enhancing immunogenicity of antigens through sustained intradermal delivery using chitosan microneedles with a patch-dissolvable design. , 2018, Acta biomaterialia.

[31]  R Langer,et al.  New methods of drug delivery. , 1990, Science.

[32]  Hyungil Jung,et al.  Drawing lithography for microneedles: a review of fundamentals and biomedical applications. , 2012, Biomaterials.

[33]  Ryan F. Donnelly,et al.  Dissolving polymeric microneedle arrays for enhanced site‐specific acyclovir delivery , 2018, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[34]  Maelíosa T. C. McCrudden,et al.  Microneedle-Mediated Transdermal Delivery of Bevacizumab. , 2018, Molecular pharmaceutics.

[35]  R. Reid,et al.  Hydrogel drug delivery system with predictable and tunable drug release and degradation rates , 2013, Proceedings of the National Academy of Sciences.

[36]  M. R. Ravi Kumar,et al.  Polymeric Controlled Drug-Delivery Systems: Perspective Issues and Opportunities , 2001, Drug development and industrial pharmacy.

[37]  Sang Jun Moon,et al.  Fabrication of microneedle array using LIGA and hot embossing process , 2005 .

[38]  Myunggi An,et al.  Dissolving Microneedle Arrays for Transdermal Delivery of Amphiphilic Vaccines. , 2017, Small.

[39]  Metin Sitti,et al.  Recent Advances in Wearable Transdermal Delivery Systems , 2018, Advanced materials.

[40]  David L. Kaplan,et al.  Fabrication of Silk Microneedles for Controlled‐Release Drug Delivery , 2012 .

[41]  Mark R. Prausnitz,et al.  Rapidly separable microneedle patch for the sustained release of a contraceptive , 2019, Nature Biomedical Engineering.

[42]  Ryan F Donnelly,et al.  Hydrogel-forming microneedle arrays: Potential for use in minimally-invasive lithium monitoring. , 2016, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[43]  Kinam Park Controlled drug delivery systems: past forward and future back. , 2014, Journal of controlled release : official journal of the Controlled Release Society.

[44]  Stefano C. Meliga,et al.  Formulations for microprojection/microneedle vaccine delivery: Structure, strength and release profiles. , 2016, Journal of controlled release : official journal of the Controlled Release Society.

[45]  T. Tanner,et al.  Delivering drugs by the transdermal route: review and comment , 2008, Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging.

[46]  David L Kaplan,et al.  Transdermal delivery devices: fabrication, mechanics and drug release from silk. , 2013, Small.

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

[48]  Pietro Ferraro,et al.  Electro‐Drawn Drug‐Loaded Biodegradable Polymer Microneedles as a Viable Route to Hypodermic Injection , 2014 .

[49]  Bert van den Berg,et al.  Transmembrane passage of hydrophobic compounds through a protein channel wall , 2009, Nature.

[50]  Sion A. Coulman,et al.  Formulation of hydrophobic peptides for skin delivery via coated microneedles , 2017, Journal of controlled release : official journal of the Controlled Release Society.

[51]  Younan Xia,et al.  Gold nanocages covered by smart polymers for controlled release with near-infrared light , 2009, Nature materials.

[52]  Xiao Peng Zhang,et al.  Dissolvable layered microneedles with core-shell structures for transdermal drug delivery. , 2018, Materials science & engineering. C, Materials for biological applications.

[53]  D. Leake,et al.  Inhibition of CD44 gene expression in human skin models, using self-delivery short interfering RNA administered by dissolvable microneedle arrays. , 2012, Human Gene Therapy.

[54]  David J. Mooney,et al.  Designing hydrogels for controlled drug delivery. , 2016, Nature reviews. Materials.

[55]  Ryan F. Donnelly,et al.  Microneedle arrays as transdermal and intradermal drug delivery systems: Materials science, manufacture and commercial development , 2016 .

[56]  Kyoung Je Cha,et al.  Simple and cost-effective fabrication of solid biodegradable polymer microneedle arrays with adjustable aspect ratio for transdermal drug delivery using acupuncture microneedles , 2014 .

[57]  Zhen Gu,et al.  Enhanced Cancer Immunotherapy by Microneedle Patch-Assisted Delivery of Anti-PD1 Antibody. , 2016, Nano letters.

[58]  Ashok Kumar,et al.  Thermo-responsive polymers: structure and design of smart materials , 2015 .

[59]  Conor O'Mahony,et al.  Hydrogel-forming microneedle arrays exhibit antimicrobial properties: potential for enhanced patient safety. , 2013, International journal of pharmaceutics.

[60]  A. Shakya,et al.  Assessment of Th1/Th2 Bias of STING Agonists Coated on Microneedles for Possible Use in Skin Allergen Immunotherapy. , 2018, Molecular pharmaceutics.

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

[62]  Akira Yamamoto,et al.  Improvement of Transdermal Delivery of Exendin-4 Using Novel Tip-Loaded Microneedle Arrays Fabricated from Hyaluronic Acid. , 2016, Molecular pharmaceutics.

[63]  Akira Yamamoto,et al.  Development of a drug-coated microneedle array and its application for transdermal delivery of interferon alpha , 2016, Biofabrication.

[64]  Guozhong Yang,et al.  Dissolving Microneedles Loaded With Etonogestrel Microcrystal Particles for Intradermal Sustained Delivery. , 2017, Journal of pharmaceutical sciences.

[65]  Yong Taik Lim,et al.  Enhanced Cancer Vaccination by In Situ Nanomicelle-Generating Dissolving Microneedles. , 2018, ACS nano.

[66]  M. Allen,et al.  Fabrication and characterization of laser micromachined hollow microneedles , 2003, TRANSDUCERS '03. 12th International Conference on Solid-State Sensors, Actuators and Microsystems. Digest of Technical Papers (Cat. No.03TH8664).

[67]  M. Allen,et al.  Microfabricated microneedles: a novel approach to transdermal drug delivery. , 1998, Journal of pharmaceutical sciences.

[68]  WonHyoung Ryu,et al.  Intracorneal injection of a detachable hybrid microneedle for sustained drug delivery. , 2018, Acta biomaterialia.

[69]  P. A. Shah,et al.  Natural biodegradable polymers based nano‐formulations for drug delivery: A review , 2019, International journal of pharmaceutics.

[70]  Jon A. Rowley,et al.  Controlling Mechanical and Swelling Properties of Alginate Hydrogels Independently by Cross-Linker Type and Cross-Linking Density , 2000 .

[71]  Fazal Haq,et al.  Preparation, properties and challenges of the microneedles-based insulin delivery system. , 2018, Journal of controlled release : official journal of the Controlled Release Society.

[72]  Kuan-Wen Wang,et al.  Near-infrared light-responsive composite microneedles for on-demand transdermal drug delivery. , 2015, Biomacromolecules.

[73]  J. Moan,et al.  Microneedle Pre-treatment of Human Skin Improves 5-Aminolevulininc Acid (ALA)- and 5-Aminolevulinic Acid Methyl Ester (MAL)-Induced PpIX Production for Topical Photodynamic Therapy Without Increase in Pain or Erythema , 2010, Pharmaceutical Research.

[74]  G. Kwon,et al.  pH- and ion-sensitive polymers for drug delivery , 2013, Expert opinion on drug delivery.

[75]  Daniel E. Otzen,et al.  Protein drug stability: a formulation challenge , 2005, Nature Reviews Drug Discovery.

[76]  Jung-Hwan Park,et al.  Bleomycin-Coated Microneedles for Treatment of Warts , 2016, Pharmaceutical Research.

[77]  Maelíosa T. C. McCrudden,et al.  In vivo studies investigating biodistribution of nanoparticle-encapsulated rhodamine B delivered via dissolving microneedles , 2017, Journal of controlled release : official journal of the Controlled Release Society.

[78]  Zhenguo Liu,et al.  Dissolving and biodegradable microneedle technologies for transdermal sustained delivery of drug and vaccine , 2013, Drug design, development and therapy.

[79]  Paula T Hammond,et al.  Synthetic Charge-Invertible Polymer for Rapid and Complete Implantation of Layer-by-Layer Microneedle Drug Films for Enhanced Transdermal Vaccination. , 2018, ACS nano.

[80]  Anders Axelsson,et al.  The mechanisms of drug release in poly(lactic-co-glycolic acid)-based drug delivery systems--a review. , 2011, International journal of pharmaceutics.

[81]  J. Matriano,et al.  Parathyroid Hormone (1-34)-Coated Microneedle Patch System: Clinical Pharmacokinetics and Pharmacodynamics for Treatment of Osteoporosis , 2010, Pharmaceutical Research.

[82]  Jonathan R. Soucy,et al.  Advances in Receptor‐Mediated, Tumor‐Targeted Drug Delivery , 2018, Advanced therapeutics.

[83]  A. Metters,et al.  Hydrogels in controlled release formulations: network design and mathematical modeling. , 2006, Advanced drug delivery reviews.

[84]  M. Prausnitz,et al.  A Microneedle Patch for Measles and Rubella Vaccination Is Immunogenic and Protective in Infant Rhesus Macaques , 2018, The Journal of infectious diseases.

[85]  S. Venkatraman,et al.  Sustained-release from nanocarriers: a review. , 2014, Journal of controlled release : official journal of the Controlled Release Society.

[86]  Zijing Li,et al.  Microneedles for transdermal delivery of insulin , 2015 .

[87]  M. Skwarczynski,et al.  Polymers for subunit vaccine delivery , 2019, European Polymer Journal.

[88]  Mark R Prausnitz,et al.  Tolerability, usability and acceptability of dissolving microneedle patch administration in human subjects. , 2017, Biomaterials.

[89]  Ulrich S. Schubert,et al.  Thermoresponsive polymers with lower critical solution temperature: from fundamental aspects and measuring techniques to recommended turbidimetry conditions , 2017 .

[90]  P. Schultz,et al.  Engineering a long-acting, potent GLP-1 analog for microstructure-based transdermal delivery , 2016, Proceedings of the National Academy of Sciences.

[91]  Ryan F. Donnelly,et al.  Microneedles: A New Frontier in Nanomedicine Delivery , 2016, Pharmaceutical Research.

[92]  Mei-Chin Chen,et al.  Sodium Hyaluronate/Chitosan Composite Microneedles as a Single-Dose Intradermal Immunization System. , 2018, Biomacromolecules.

[93]  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.

[94]  Shuwang He,et al.  Recent progress of micro-needle formulations: Fabrication strategies and delivery applications , 2019, Journal of Drug Delivery Science and Technology.

[95]  W. Kao,et al.  Drug release kinetics and transport mechanisms of non-degradable and degradable polymeric delivery systems , 2010, Expert opinion on drug delivery.

[96]  Cato T Laurencin,et al.  Biomedical Applications of Biodegradable Polymers. , 2011, Journal of polymer science. Part B, Polymer physics.

[97]  Hyungil Jung,et al.  Anti‐obesity effect of a novel caffeine‐loaded dissolving microneedle patch in high‐fat diet‐induced obese C57BL/6J mice , 2017, Journal of controlled release : official journal of the Controlled Release Society.

[98]  Guohua Jiang,et al.  Fabrication of biodegradable composite microneedles based on calcium sulfate and gelatin for transdermal delivery of insulin. , 2017, Materials science & engineering. C, Materials for biological applications.

[99]  Weiyue Huang,et al.  Fabrication of Tip-Dissolving Microneedles for Transdermal Drug Delivery of Meloxicam , 2017, AAPS PharmSciTech.

[100]  Hyungil Jung,et al.  Dissolving microneedles for transdermal drug administration prepared by stepwise controlled drawing of maltose. , 2011, Biomaterials.

[101]  Hyungil Jung,et al.  The Troy Microneedle: A Rapidly Separating, Dissolving Microneedle Formed by Cyclic Contact and Drying on the Pillar (CCDP) , 2015, PloS one.

[102]  Thakur Raghu Raj Singh,et al.  Hydrogel-Forming Microneedle Arrays for Enhanced Transdermal Drug Delivery , 2012, Advanced functional materials.

[103]  L. Schmidt‐Mende,et al.  ZnO - nanostructures, defects, and devices , 2007 .

[104]  A. Caliò,et al.  Polymeric microneedles based enzymatic electrodes for electrochemical biosensing of glucose and lactic acid , 2016 .

[105]  Maelíosa T. C. McCrudden,et al.  Transdermal delivery of gentamicin using dissolving microneedle arrays for potential treatment of neonatal sepsis , 2017, Journal of controlled release : official journal of the Controlled Release Society.

[106]  M. Allen,et al.  Microfabricated microneedles for gene and drug delivery. , 2000, Annual review of biomedical engineering.

[107]  Yukako Ito,et al.  Two-layered dissolving microneedles for percutaneous delivery of sumatriptan in rats , 2011, Drug development and industrial pharmacy.

[108]  Eneko Larrañeta,et al.  Hydrogel-Forming Microneedle Arrays Made from Light-Responsive Materials for On-Demand Transdermal Drug Delivery. , 2016, Molecular pharmaceutics.

[109]  Robert Langer,et al.  Bioresponsive materials , 2016 .

[110]  Jayanth Panyam,et al.  Intradermal delivery of vaccine nanoparticles using hollow microneedle array generates enhanced and balanced immune response. , 2019, Journal of controlled release : official journal of the Controlled Release Society.

[111]  Eneko Larrañeta,et al.  Novel nanosuspension‐based dissolving microneedle arrays for transdermal delivery of a hydrophobic drug , 2018, Journal of interdisciplinary nanomedicine.

[112]  Dan Dan Zhu,et al.  Insulin delivery systems combined with microneedle technology. , 2018, Advanced drug delivery reviews.

[113]  M. Minhas,et al.  Evaluation of microneedles-assisted in situ depot forming poloxamer gels for sustained transdermal drug delivery , 2019, Drug Delivery and Translational Research.

[114]  Guohua Jiang,et al.  Microneedles fabricated from alginate and maltose for transdermal delivery of insulin on diabetic rats. , 2018, Materials science & engineering. C, Materials for biological applications.

[115]  Yatin R. Gokarn,et al.  Non-invasive delivery strategies for biologics , 2018, Nature Reviews Drug Discovery.

[116]  M. Prausnitz,et al.  Rabies vaccination in dogs using a dissolving microneedle patch. , 2016, Journal of controlled release : official journal of the Controlled Release Society.

[117]  Yuqin Qiu,et al.  Systemic delivery of artemether by dissolving microneedles. , 2016, International journal of pharmaceutics.

[118]  Zhen Gu,et al.  Hypoxia-Sensitive Materials for Biomedical Applications , 2016, Annals of Biomedical Engineering.

[119]  M. Prausnitz,et al.  A microneedle patch containing measles vaccine is immunogenic in non-human primates. , 2015, Vaccine.

[120]  Ali Khademhosseini,et al.  Biodegradable Gelatin Methacryloyl Microneedles for Transdermal Drug Delivery , 2018, Advanced healthcare materials.

[121]  Amit Jain,et al.  Microneedles enhance topical delivery of 15‐deoxy‐&Dgr;12,14‐prostaglandin J2 and reduce nociception in temporomandibular joint of rats , 2017, Journal of controlled release : official journal of the Controlled Release Society.

[122]  Hui Li,et al.  Microneedles As a Delivery System for Gene Therapy , 2016, Front. Pharmacol..

[123]  Robert Langer,et al.  Emerging Frontiers in Drug Delivery. , 2016, Journal of the American Chemical Society.

[124]  Yeu‐Chun Kim,et al.  CD44 targeting biocompatible and biodegradable hyaluronic acid cross‐linked zein nanogels for curcumin delivery to cancer cells: In vitro and in vivo evaluation , 2018, Journal of controlled release : official journal of the Controlled Release Society.

[125]  Karmen Cheung,et al.  Microneedles for drug delivery: trends and progress , 2016, Drug delivery.

[126]  X Huang,et al.  On the importance and mechanisms of burst release in matrix-controlled drug delivery systems. , 2001, Journal of controlled release : official journal of the Controlled Release Society.

[127]  Albert P. Pisano,et al.  Polymer investment molding: Method for fabricating hollow, microscale parts , 2007 .

[128]  S. Tverdokhlebov,et al.  Plasma treatment as an efficient tool for controlled drug release from polymeric materials: A review , 2017, Journal of controlled release : official journal of the Controlled Release Society.

[129]  Ryan F. Donnelly,et al.  Hydrogel-Forming Microneedles Prepared from “Super Swelling” Polymers Combined with Lyophilised Wafers for Transdermal Drug Delivery , 2014, PloS one.

[130]  Eneko Larrañeta,et al.  Slowly dissolving intradermal microneedles , 2019, Nature Biomedical Engineering.

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

[132]  A. Pavlou,et al.  Recombinant protein therapeutics—success rates, market trends and values to 2010 , 2004, Nature Biotechnology.

[133]  Michel Cormier,et al.  Microneedle-based vaccines. , 2009, Current topics in microbiology and immunology.

[134]  Feng Xu,et al.  Recent advances of controlled drug delivery using microfluidic platforms☆ , 2017, Advanced drug delivery reviews.

[135]  Zhen Gu,et al.  Polymeric microneedles for transdermal protein delivery☆ , 2018, Advanced drug delivery reviews.

[136]  R. Langer,et al.  Drug delivery and targeting. , 1998, Nature.

[137]  Xi Xie,et al.  Microneedle-Mediated Delivery of Lipid-Coated Cisplatin Nanoparticles for Efficient and Safe Cancer Therapy. , 2018, ACS applied materials & interfaces.

[138]  S. Kundu,et al.  Insulin-Loaded Silk Fibroin Microneedles as Sustained Release System. , 2019, ACS biomaterials science & engineering.

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

[140]  Seong Ho Kang,et al.  Improvement in antigen-delivery using fabrication of a grooves-embedded microneedle array , 2009 .

[141]  Study on Mechanical Properties for Modeling and Simulation of Microneedles for Medical Applications , 2013 .

[142]  William B. Liechty,et al.  Polymers for drug delivery systems. , 2010, Annual review of chemical and biomolecular engineering.

[143]  Guohua Jiang,et al.  Near-infrared light triggered and separable microneedles for transdermal delivery of metformin in diabetic rats. , 2017, Journal of materials chemistry. B.

[144]  Maelíosa T. C. McCrudden,et al.  Microneedles for intradermal and transdermal drug delivery. , 2013, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[145]  Maelíosa T. C. McCrudden,et al.  Hydrogel-forming microneedles enhance transdermal delivery of metformin hydrochloride , 2018, Journal of controlled release : official journal of the Controlled Release Society.

[146]  Mark R. Prausnitz,et al.  Dissolving Polymer Microneedle Patches for Influenza Vaccination , 2010, Nature Medicine.

[147]  Xiao Wei,et al.  Polymer‐based drug delivery systems for cancer treatment , 2016 .

[148]  Cansel Tuncer,et al.  pH-Responsive polymers , 2017 .

[149]  O. Farokhzad,et al.  Degradable Controlled-Release Polymers and Polymeric Nanoparticles: Mechanisms of Controlling Drug Release. , 2016, Chemical reviews.

[150]  D. Maisels,et al.  Silicon granuloma of the skin and subcutaneous tissues. , 1966, American journal of surgery.

[151]  Joseph M. DeSimone,et al.  Single-Step Fabrication of Computationally Designed Microneedles by Continuous Liquid Interface Production , 2016, PloS one.

[152]  T. Mehta,et al.  Microneedles: an emerging transdermal drug delivery system , 2012, The Journal of pharmacy and pharmacology.

[153]  Dennis Douroumis,et al.  3D printed microneedles for insulin skin delivery , 2018, International journal of pharmaceutics.

[154]  Brett E. Bouma,et al.  A Bio-Inspired Swellable Microneedle Adhesive for Mechanical Interlocking with Tissue , 2013, Nature Communications.

[155]  Y. Demir,et al.  Sodium Alginate Microneedle Arrays Mediate the Transdermal Delivery of Bovine Serum Albumin , 2013, PloS one.

[156]  Guohua Jiang,et al.  Fabrication of Dissolving Microneedles with Thermal-Responsive Coating for NIR-Triggered Transdermal Delivery of Metformin on Diabetic Rats. , 2018, ACS biomaterials science & engineering.

[157]  Mary-Carmel Kearney,et al.  Microneedle-mediated delivery of donepezil: Potential for improved treatment options in Alzheimer's disease. , 2016, European journal of pharmaceutics and biopharmaceutics.

[158]  Courtney Jarrahian,et al.  Opportunities and challenges in delivering influenza vaccine by microneedle patch. , 2015, Vaccine.

[159]  Mark R. Prausnitz,et al.  Collection of Analytes from Microneedle Patches , 2014, Analytical chemistry.

[160]  Wim Jiskoot,et al.  IgG-loaded hyaluronan-based dissolving microneedles for intradermal protein delivery. , 2015, Journal of controlled release : official journal of the Controlled Release Society.

[161]  U. O. Hafeli,et al.  Hollow Out-of-Plane Polymer Microneedles Made by Solvent Casting for Transdermal Drug Delivery , 2012, Journal of Microelectromechanical Systems.

[162]  Shih-Feng Chou,et al.  Current strategies for sustaining drug release from electrospun nanofibers. , 2015, Journal of controlled release : official journal of the Controlled Release Society.

[163]  K. Tu,et al.  Rapid prototyping of biodegradable microneedle arrays by integrating CO2 laser processing and polymer molding , 2016 .

[164]  Jung-Hwan Park,et al.  Hydrogel swelling as a trigger to release biodegradable polymer microneedles in skin. , 2012, Biomaterials.

[165]  C. Giaquinto,et al.  Vaccine impact: Benefits for human health. , 2016, Vaccine.

[166]  Marco Rolandi,et al.  Chitin Microneedles for an Easy‐to‐Use Tuberculosis Skin Test , 2014, Advanced healthcare materials.

[167]  R. Donnelly,et al.  Dissolving microneedles for intradermal vaccination: manufacture, formulation, and stakeholder considerations , 2018, Expert opinion on drug delivery.

[168]  J. Bos,et al.  The 500 Dalton rule for the skin penetration of chemical compounds and drugs , 2000, Experimental dermatology.

[169]  E. Marin,et al.  Critical evaluation of biodegradable polymers used in nanodrugs , 2013, International journal of nanomedicine.

[170]  Arezou Aghabegi Moghanjoughi,et al.  A concise review on smart polymers for controlled drug release , 2016, Drug Delivery and Translational Research.

[171]  Keizo Fukushima,et al.  Two-layered dissolving microneedles formulated with intermediate-acting insulin. , 2012, International journal of pharmaceutics.

[172]  Keizo Fukushima,et al.  Two-Layered Dissolving Microneedles for Percutaneous Delivery of Peptide/Protein Drugs in Rats , 2010, Pharmaceutical Research.

[173]  Firas Sammoura,et al.  Polymeric microneedle fabrication using a microinjection molding technique , 2007 .

[174]  Yunhua Gao,et al.  Dissolving microneedle-based intradermal delivery of interferon-α-2b , 2016, Drug development and industrial pharmacy.

[175]  Hyungil Jung,et al.  Innovative polymeric system (IPS) for solvent-free lipophilic drug transdermal delivery via dissolving microneedles. , 2016, Journal of controlled release : official journal of the Controlled Release Society.

[176]  C. DeForest,et al.  Photoresponsive biomaterials for targeted drug delivery and 4D cell culture , 2018 .

[177]  Hansoo Park,et al.  Microneedles: A versatile strategy for transdermal delivery of biological molecules. , 2017, International journal of biological macromolecules.

[178]  J. Bouwstra,et al.  Hollow microneedle‐mediated intradermal delivery of model vaccine antigen‐loaded PLGA nanoparticles elicits protective T cell‐mediated immunity to an intracellular bacterium , 2017, Journal of controlled release : official journal of the Controlled Release Society.

[179]  Anthony Guiseppi-Elie,et al.  Bioresponsive Hydrogels , 2013, Advanced healthcare materials.

[180]  Jung-Hwan Park,et al.  Microneedles for drug and vaccine delivery. , 2012, Advanced drug delivery reviews.

[181]  Zhiyong Qian,et al.  Near‐Infrared Responsive PEGylated Gold Nanorod and Doxorubicin Loaded Dissolvable Hyaluronic Acid Microneedles for Human Epidermoid Cancer Therapy , 2018 .