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Mark R Prausnitz - One of the best experts on this subject based on the ideXlab platform.

  • Evaluation of Microneedles in Human Subjects
    Percutaneous Penetration Enhancers Physical Methods in Penetration Enhancement, 2017
    Co-Authors: Haripriya Kalluri, James J. Norman, Seong-o Choi, Mark R Prausnitz
    Abstract:

    Microneedles have been studied extensively in vitro and in animals. Here we review the growing collection of microneedle studies involving human subjects. Human studies seek to validate microneedle performance and safety, including microneedle insertion into the skin, liquid infusion via hollow Microneedles, pain associated with solid and hollow Microneedles, safety, and skin resealing. Human studies have also assessed drug and vaccine delivery, including small molecules like naltrexone, methyl nicotinate, lidocaine and dyclonine, and aminolevulinic acid and methyl aminolevulinate; peptides and proteins like parathyroid hormone and insulin; and vaccines, especially influenza. Patient and provider preferences have been collected on topics such as general opinion of Microneedles, willingness to vaccinate using Microneedles, willingness to self-administer Microneedles, and concerns about Microneedles. Overall, these studies validate preclinical findings that Microneedles offer a powerful new approach to human medical applications.

  • Intrastromal delivery of bevacizumab using Microneedles to treat corneal neovascularization
    Investigative ophthalmology & visual science, 2014
    Co-Authors: Yoo C. Kim, Henry F Edelhauser, Hans E. Grossniklaus, Mark R Prausnitz
    Abstract:

    PURPOSE: This study tested the hypothesis that highly targeted intrastromal delivery of bevacizumab using coated Microneedles allows dramatic dose sparing compared with subconjunctival and topical delivery for treatment of corneal neovascularization.\n\nMETHODS: Stainless steel Microneedles 400 μm in length were coated with bevacizumab. A silk suture was placed in the cornea approximately 1 mm from the limbus to induce corneal neovascularization in the eyes of New Zealand white rabbits that were divided into different groups: untreated, microneedle delivery, topical eye drop, and subconjunctival injection of bevacizumab. All drug treatments were initiated 4 days after suture placement and area of neovascularization was measured daily by digital photography for 18 days.\n\nRESULTS: Eyes treated once with 4.4 μg bevacizumab using Microneedles reduced neovascularization compared with untreated eyes by 44% (day 18). Eyes treated once with 2500 μg bevacizumab using subconjunctival injection gave similar results to microneedle-treated eyes. Eyes treated once with 4.4 μg subconjunctival bevacizumab showed no significant effect compared with untreated eyes. Eyes treated with 52,500 μg bevacizumab by eye drops three times per day for 14 days reduced the neovascularization area compared with untreated eyes by 6% (day 18), which was significantly less effective than the single microneedle treatment. Visual exam and histological analysis showed no observable effect of microneedle treatment on corneal transparency or microanatomical structure.\n\nCONCLUSIONS: This study shows that Microneedles can target drug delivery to corneal stroma in a minimally invasive way and demonstrates effective suppression of corneal neovascularization after suture-induced injury using a much lower dose compared with conventional methods.

  • Hollow Microneedles for intradermal injection fabricated by sacrificial micromolding and selective electrodeposition
    Biomedical Microdevices, 2013
    Co-Authors: James J. Norman, Seong-o Choi, Nhien T. Tong, Avishek R. Aiyar, Samirkumar R. Patel, Mark R Prausnitz, Mark G. Allen
    Abstract:

    Limitations with standard intradermal injections have created a clinical need for an alternative, low-cost injection device. In this study, we designed a hollow metal microneedle for reliable intradermal injection and developed a high-throughput micromolding process to produce metal Microneedles with complex geometries. To fabricate the Microneedles, we laser-ablated a 70 μm × 70 μm square cavity near the tip of poly(lactic acid) (PLA) Microneedles. The master structure was a template for multiple micromolded poly(lactic acid-co-glycolic acid) (PLGA) replicas. Each replica was sputtered with a gold seed layer with minimal gold deposited in the cavity due to masking effects. In this way, nickel was electrodeposited selectively outside of the cavity, after which the polymer replica was dissolved to produce a hollow metal microneedle. Force-displacement tests showed the Microneedles, with 12 μm thick electrodeposition, could penetrate skin with an insertion force 9 times less than their axial failure force. We injected fluid with the Microneedles into pig skin in vitro and hairless guinea pig skin in vivo. The injections targeted 90 % of the material within the skin with minimal leakage onto the skin surface. We conclude that hollow Microneedles made by this simple microfabrication method can achieve targeted intradermal injection.

  • Microneedles for drug and vaccine delivery
    Advanced Drug Delivery Reviews, 2012
    Co-Authors: Jung Hwan Park, Mark R Prausnitz
    Abstract:

    Abstract Microneedles were first conceptualized for drug delivery many decades ago, but only became the subject of significant research starting in the mid-1990's when microfabrication technology enabled their manufacture as (i) solid Microneedles for skin pretreatment to increase skin permeability, (ii) Microneedles coated with drug that dissolves off in the skin, (iii) polymer Microneedles that encapsulate drug and fully dissolve in the skin and (iv) hollow Microneedles for drug infusion into the skin. As shown in more than 350 papers now published in the field, Microneedles have been used to deliver a broad range of different low molecular weight drugs, biotherapeutics and vaccines, including published human studies with a number of small-molecule and protein drugs and vaccines. Influenza vaccination using a hollow microneedle is in widespread clinical use and a number of solid microneedle products are sold for cosmetic purposes. In addition to applications in the skin, Microneedles have also been adapted for delivery of bioactives into the eye and into cells. Successful application of Microneedles depends on device function that facilitates microneedle insertion and possible infusion into skin, skin recovery after microneedle removal, and drug stability during manufacturing, storage and delivery, and on patient outcomes, including lack of pain, skin irritation and skin infection, in addition to drug efficacy and safety. Building off a strong technology base and multiple demonstrations of successful drug delivery, Microneedles are poised to advance further into clinical practice to enable better pharmaceutical therapies, vaccination and other applications.

  • stability of influenza vaccine coated onto Microneedles
    Biomaterials, 2012
    Co-Authors: Hyo Jick Choi, Brian J. Bondy, Fu-shi Quan, Sang-moo Kang, Richard W. Compans, Mark R Prausnitz
    Abstract:

    A microneedle patch coated with vaccine simplifies vaccination by using a patch-based delivery method and targets vaccination to the skin for superior immunogenicity compared to intramuscular injection. Previous studies of Microneedles have demonstrated effective vaccination using freshly prepared Microneedles, but the issue of long-term vaccine stability has received only limited attention. Here, we studied the long-term stability of Microneedles coated with whole inactivated influenza vaccine guided by the hypothesis that crystallization and phase separation of the microneedle coating matrix damages influenza vaccine coated onto Microneedles. In vitro studies showed that the vaccine lost stability as measured by hemagglutination activity in proportion to the degree of coating matrix crystallization and phase separation. Transmission electron microscopy similarly showed damaged morphology of the inactivated virus vaccine associated with crystallization. In vivo assessment of immune response and protective efficacy in mice further showed reduced vaccine immunogenicity after influenza vaccination using Microneedles with crystallized or phase-separated coatings. This work shows that crystallization and phase separation of the dried coating matrix are important factors affecting long-term stability of influenza vaccine-coated Microneedles.

Jung Hwan Park - One of the best experts on this subject based on the ideXlab platform.

  • Microneedles for drug and vaccine delivery
    Advanced Drug Delivery Reviews, 2012
    Co-Authors: Jung Hwan Park, Mark R Prausnitz
    Abstract:

    Abstract Microneedles were first conceptualized for drug delivery many decades ago, but only became the subject of significant research starting in the mid-1990's when microfabrication technology enabled their manufacture as (i) solid Microneedles for skin pretreatment to increase skin permeability, (ii) Microneedles coated with drug that dissolves off in the skin, (iii) polymer Microneedles that encapsulate drug and fully dissolve in the skin and (iv) hollow Microneedles for drug infusion into the skin. As shown in more than 350 papers now published in the field, Microneedles have been used to deliver a broad range of different low molecular weight drugs, biotherapeutics and vaccines, including published human studies with a number of small-molecule and protein drugs and vaccines. Influenza vaccination using a hollow microneedle is in widespread clinical use and a number of solid microneedle products are sold for cosmetic purposes. In addition to applications in the skin, Microneedles have also been adapted for delivery of bioactives into the eye and into cells. Successful application of Microneedles depends on device function that facilitates microneedle insertion and possible infusion into skin, skin recovery after microneedle removal, and drug stability during manufacturing, storage and delivery, and on patient outcomes, including lack of pain, skin irritation and skin infection, in addition to drug efficacy and safety. Building off a strong technology base and multiple demonstrations of successful drug delivery, Microneedles are poised to advance further into clinical practice to enable better pharmaceutical therapies, vaccination and other applications.

  • Microneedles for drug and vaccine delivery
    Advanced Drug Delivery Reviews, 2012
    Co-Authors: Yeu Chun Kim, Jung Hwan Park, Mark R Prausnitz
    Abstract:

    Microneedles were first conceptualized for drug delivery many decades ago, but only became the subject of significant research starting in the mid-1990's when microfabrication technology enabled their manufacture as (i) solid Microneedles for skin pretreatment to increase skin permeability, (ii) Microneedles coated with drug that dissolves off in the skin, (iii) polymer Microneedles that encapsulate drug and fully dissolve in the skin and (iv) hollow Microneedles for drug infusion into the skin. As shown in more than 350 papers now published in the field, Microneedles have been used to deliver a broad range of different low molecular weight drugs, biotherapeutics and vaccines, including published human studies with a number of small-molecule and protein drugs and vaccines. Influenza vaccination using a hollow microneedle is in widespread clinical use and a number of solid microneedle products are sold for cosmetic purposes. In addition to applications in the skin, Microneedles have also been adapted for delivery of bioactives into the eye and into cells. Successful application of Microneedles depends on device function that facilitates microneedle insertion and possible infusion into skin, skin recovery after microneedle removal, and drug stability during manufacturing, storage and delivery, and on patient outcomes, including lack of pain, skin irritation and skin infection, in addition to drug efficacy and safety. Building off a strong technology base and multiple demonstrations of successful drug delivery, Microneedles are poised to advance further into clinical practice to enable better pharmaceutical therapies, vaccination and other applications. © 2012 Elsevier B.V.

  • Hydrogel swelling as a trigger to release biodegradable polymer Microneedles in skin
    Biomaterials, 2012
    Co-Authors: Min Young Kim, Bokyung Jung, Jung Hwan Park
    Abstract:

    Biodegradable polymeric Microneedles were developed as a method for achieving sustained transdermal drug release. These Microneedles have potential as a patient-friendly substitute for conventional sustained release methods. However, they have limitations related to the difficulty of achieving separation of the needles into the skin. We demonstrated that microneedle separation into the skin was mediated by hydrogel swelling in response to contact with body fluid after the needles were inserted into the skin. The hydrogel microparticles were synthesized by an emulsification method using poly-N-isopropylacrylamide (PNIPAAm). The Microneedles were fabricated by micromolding poly-lactic-co-glycolic acid (PLGA) after filling the cavities of the mold with the hydrogel microparticles. The failure of microneedle tips caused by hydrogel swelling was studied in regard to contact with water, insertion of Microneedles into porcine cadaver skin in vitro, stress-strain behavior, and insertion into the back skin of a hairless mouse in vivo. The drug delivery property of the hydrogel particles was investigated qualitatively by inserting polymer Microneedles into porcine cadaver skin in vitro, and the sustained release property of PLGA Microneedles containing hydrogel microparticles was studied quantitatively using the Franz cell model. The hydrogel particles absorbed water quickly, resulting in the cracking of the Microneedles due to the difference in volume expansion between the needle matrix polymer and the hydrogel particles. The swollen particles caused the Microneedles to totally breakdown, leaving the microneedle tips in the porcine cadaver skin in vitro and in the hairless mouse skin in vivo. Model drugs encapsulated in biodegradable polymer Microneedles and hydrogel microparticles were successfully delivered by releasing Microneedles into the skin. © 2011 Elsevier Ltd.

  • hydrogel swelling as a trigger to release biodegradable polymer Microneedles in skin
    Biomaterials, 2012
    Co-Authors: Bokyung Jung, Jung Hwan Park
    Abstract:

    Abstract Biodegradable polymeric Microneedles were developed as a method for achieving sustained transdermal drug release. These Microneedles have potential as a patient-friendly substitute for conventional sustained release methods. However, they have limitations related to the difficulty of achieving separation of the needles into the skin. We demonstrated that microneedle separation into the skin was mediated by hydrogel swelling in response to contact with body fluid after the needles were inserted into the skin. The hydrogel microparticles were synthesized by an emulsification method using poly-N-isopropylacrylamide (PNIPAAm). The Microneedles were fabricated by micromolding poly-lactic-co-glycolic acid (PLGA) after filling the cavities of the mold with the hydrogel microparticles. The failure of microneedle tips caused by hydrogel swelling was studied in regard to contact with water, insertion of Microneedles into porcine cadaver skin in vitro, stress–strain behavior, and insertion into the back skin of a hairless mouse in vivo. The drug delivery property of the hydrogel particles was investigated qualitatively by inserting polymer Microneedles into porcine cadaver skin in vitro, and the sustained release property of PLGA Microneedles containing hydrogel microparticles was studied quantitatively using the Franz cell model. The hydrogel particles absorbed water quickly, resulting in the cracking of the Microneedles due to the difference in volume expansion between the needle matrix polymer and the hydrogel particles. The swollen particles caused the Microneedles to totally breakdown, leaving the microneedle tips in the porcine cadaver skin in vitro and in the hairless mouse skin in vivo. Model drugs encapsulated in biodegradable polymer Microneedles and hydrogel microparticles were successfully delivered by releasing Microneedles into the skin.

  • a microneedle roller for transdermal drug delivery
    European Journal of Pharmaceutics and Biopharmaceutics, 2010
    Co-Authors: Jung Hwan Park, Seong-o Choi, Young Bin Choy, Mark R Prausnitz
    Abstract:

    Abstract Microneedle rollers have been used to treat large areas of skin for cosmetic purposes and to increase skin permeability for drug delivery. In this study, we introduce a polymer microneedle roller fabricated by inclined rotational UV lithography, replicated by micromolding hydrophobic polylactic acid and hydrophilic carboxy-methyl-cellulose. These Microneedles created micron-scale holes in human and porcine cadaver skin that permitted entry of acetylsalicylic acid, Trypan blue and nanoparticles measuring 50 nm and 200 nm in diameter. The amount of acetylsalicylic acid delivered increased with the number of holes made in the skin and was 1–2 orders of magnitude greater than in untreated skin. Lateral diffusion in the skin between holes made by Microneedles followed expected diffusional kinetics, with effective diffusivity values that were 23–160 times smaller than in water. Compared to inserting Microneedles on a flat patch, the sequential insertion of Microneedles row by row on a roller required less insertion force in full-thickness porcine skin. Overall, polymer microneedle rollers, prepared from replicated polymer films, offer a simple way to increase skin permeability for drug delivery.

Kenji Sugibayashi - One of the best experts on this subject based on the ideXlab platform.

  • effects of pretreatment of needle puncture and sandpaper abrasion on the in vitro skin permeation of fluorescein isothiocyanate fitc dextran
    International Journal of Pharmaceutics, 2006
    Co-Authors: Xue Ming Wu, Hiroaki Todo, Kenji Sugibayashi
    Abstract:

    Microneedle systems have gained attention as having many advantages over transdermal patches and hypodermic needles. The procedure provides adequate skin permeation rates without pain or severe infection. To obtain information for designing a microneedle system, macroneedles were used instead of Microneedles to investigate the effects of pretreatment of needle puncture in the skin barrier stratum corneum on in vitro skin permeation of fluorescein isothiocyanate (FITC)-dextrans (4.3, 9.6 and 42.0 kDa) (FD-4, FD-10 and FD-40). The effect of sandpaper abrasion was also investigated for comparison. Both pretreatments on the skin barrier significantly increased the skin permeation of FDs. Lactate dehydrogenase (LDH) leaching was measured after pretreatment of macroneedle and sandpaper abrasion on the skin to evaluate the skin damage by these pretreatment methods. Lower leaching of LDH was observed after macroneedle puncture than after sandpaper abrasion. Next, a parallel permeation-resistance model of the skin barrier was established. Skin permeation of FD-10 was predicted by the model as a function of the number of pores in the skin barrier. Our results suggest that needle puncture may provide a safe, efficient and controllable alternative for increasing transdermal drug delivery.

  • Effects of pretreatment of needle puncture and sandpaper abrasion on the in vitro skin permeation of fluorescein isothiocyanate (FITC)-dextran
    International Journal of Pharmaceutics, 2006
    Co-Authors: Xue Ming Wu, Hiroaki Todo, Kenji Sugibayashi
    Abstract:

    Microneedle systems have gained attention as having many advantages over transdermal patches and hypodermic needles. The procedure provides adequate skin permeation rates without pain or severe infection. To obtain information for designing a microneedle system, macroneedles were used instead of Microneedles to investigate the effects of pretreatment of needle puncture in the skin barrier stratum corneum on in vitro skin permeation of fluorescein isothiocyanate (FITC)-dextrans (4.3, 9.6 and 42.0 kDa) (FD-4, FD-10 and FD-40). The effect of sandpaper abrasion was also investigated for comparison. Both pretreatments on the skin barrier significantly increased the skin permeation of FDs. Lactate dehydrogenase (LDH) leaching was measured after pretreatment of macroneedle and sandpaper abrasion on the skin to evaluate the skin damage by these pretreatment methods. Lower leaching of LDH was observed after macroneedle puncture than after sandpaper abrasion. Next, a parallel permeation-resistance model of the skin barrier was established. Skin permeation of FD-10 was predicted by the model as a function of the number of pores in the skin barrier. Our results suggest that needle puncture may provide a safe, efficient and controllable alternative for increasing transdermal drug delivery. © 2006 Elsevier B.V. All rights reserved.

Harvinder S. Gill - One of the best experts on this subject based on the ideXlab platform.

  • Microneedle Coating Methods: A Review with a Perspective.
    Journal of Pharmacology and Experimental Therapeutics, 2019
    Co-Authors: Rohan S.j. Ingrole, Harvinder S. Gill
    Abstract:

    A coated microneedle array comprises sharp micrometer-sized needle shafts attached to a base substrate and coated with a drug on their surfaces. Coated Microneedles are under investigation for drug delivery into the skin and other tissues, and a broad assortment of active materials, including small molecules, peptides, proteins, deoxyribonucleic acids, and viruses, have been coated onto Microneedles. To coat the Microneedles, different methods have been developed. Some coating methods achieve selective coating of just the microneedle shafts, whereas other methods coat not only microneedle shafts but also the array base substrate. Selective coating of just the microneedle shafts is more desirable since it provides control over drug dosage, prevents drug waste, and offers high delivery efficiency. Different excipients are added to the coating liquid to modulate its viscosity and surface tension in order to achieve uniform coatings on Microneedles. Coated Microneedles have been used in a broad range of biomedical applications. To highlight these different applications, a table summarizing the different active materials and the amounts coated on Microneedles is provided. We also discuss factors that should be considered when deciding suitability of coated Microneedles for new-drug delivery applications. In recent years, many coated Microneedles have been investigated in human clinical trials, and there is now a strong effort to bring the first coated microneedle-based product to market.

  • kinetics of skin resealing after insertion of Microneedles in human subjects
    Journal of Controlled Release, 2011
    Co-Authors: Jyoti Gupta, Samantha N. Andrews, Harvinder S. Gill, Mark R Prausnitz
    Abstract:

    Over the past decade, Microneedles have been shown to dramatically increase skin permeability to a broad range of compounds by creating reversible microchannels in the skin. However, in order to achieve sustained transdermal drug delivery, the extent and duration of skin's increased permeability needs to be determined. In this study, we used electrical impedance spectroscopy to perform the first experiments in human subjects to analyze the resealing of skin's barrier properties after insertion of Microneedles. Microneedles having a range of geometries were studied in conjunction with the effect of occlusion to test the hypothesis that increasing microneedle length, number, and cross-sectional area together with occlusion leads to an increase in skin resealing time that can exceed one day. Results indicated that in the absence of occlusion, all microneedle treated sites recovered barrier properties within 2 h, while occluded sites resealed more slowly, with resealing windows ranging from 3 to 40 h depending on microneedle geometry. Upon subsequent removal of occlusion, the skin barrier resealed rapidly. Longer Microneedles, increased number of needles, and larger cross-sectional area demonstrated slower resealing kinetics indicating that microneedle geometry played a significant role in the barrier resealing process. Overall, this study showed that pre-treatment of skin with Microneedles before applying an occlusive transdermal patch can increase skin permeability for more than one day, but nonetheless allow skin to reseal rapidly after patch removal.

  • Kinetics of skin resealing after insertion of Microneedles in human subjects
    Journal of Controlled Release, 2011
    Co-Authors: Jyoti Gupta, Samantha N. Andrews, Harvinder S. Gill, Mark R Prausnitz
    Abstract:

    Over the past decade, Microneedles have been shown to dramatically increase skin permeability to a broad range of compounds by creating reversible microchannels in the skin. However, in order to achieve sustained transdermal drug delivery, the extent and duration of skin's increased permeability needs to be determined. In this study, we used electrical impedance spectroscopy to perform the first experiments in human subjects to analyze the resealing of skin's barrier properties after insertion of Microneedles. Microneedles having a range of geometries were studied in conjunction with the effect of occlusion to test the hypothesis that increasing microneedle length, number, and cross-sectional area together with occlusion leads to an increase in skin resealing time that can exceed one day. Results indicated that in the absence of occlusion, all microneedle treated sites recovered barrier properties within 2 h, while occluded sites resealed more slowly, with resealing windows ranging from 3 to 40 h depending on microneedle geometry. Upon subsequent removal of occlusion, the skin barrier resealed rapidly. Longer Microneedles, increased number of needles, and larger cross-sectional area demonstrated slower resealing kinetics indicating that microneedle geometry played a significant role in the barrier resealing process. Overall, this study showed that pre-treatment of skin with Microneedles before applying an occlusive transdermal patch can increase skin permeability for more than one day, but nonetheless allow skin to reseal rapidly after patch removal. ?? 2011 Elsevier B.V. All rights reserved.

  • Effect of Microneedle Design on Pain in Human Volunteers
    The Clinical Journal of Pain, 2008
    Co-Authors: Harvinder S. Gill, Donald D. Denson, Brett A. Burris, Mark R Prausnitz
    Abstract:

    ObjectivesTo design Microneedles that minimize pain, this study tested the hypothesis that Microneedles cause significantly less pain than a 26-gauge hypodermic needle, and that decreasing microneedle length and the number of Microneedles reduces pain in normal human volunteers.MethodsSingle microne

  • Pocketed Microneedles for drug delivery to the skin
    Journal of Physics and Chemistry of Solids, 2008
    Co-Authors: Harvinder S. Gill, Mark R Prausnitz
    Abstract:

    Drug delivery to the skin is limited by the strong barrier properties of skin's outer layer of stratum corneum. Micron-scale needles have been developed to deliver drugs across this barrier layer and into the skin in a minimally invasive manner. One method of delivery involves coating these Microneedles with a drug that rapidly dissolves off within the skin. As a variation on this approach, this study examines Microneedles with holes cut through their shafts to form "pockets" that can be filled with drug formulations using a dip-coating method. Our results (i) demonstrated the filling of microneedle pockets having a variety of different sizes and shapes, (ii) quantified the amount of drug that can be filled into pockets and coated onto microneedle surfaces, (iii) developed composite microneedle structures that sequester one model drug within the microneedle pocket and coat another model drug on the microneedle surface and (iv) showed that pocketed Microneedles can deliver a model drug to a targeted depth within the skin within 1 min. We conclude that pocketed Microneedles offer unique capabilities for controlled drug delivery to the skin. © 2007.

Ming Hung Ling - One of the best experts on this subject based on the ideXlab platform.

  • fully embeddable chitosan Microneedles as a sustained release depot for intradermal vaccination
    Biomaterials, 2013
    Co-Authors: Mei Chin Chen, Shih-fang Huang, Ming Hung Ling
    Abstract:

    This study introduces a microneedle transdermal delivery system, composed of embeddable chitosan Microneedles and a poly(L-lactide-co-D,L-lactide) (PLA) supporting array, for complete and sustained delivery of encapsulated antigens to the skin. Chitosan Microneedles were mounted to the top of a strong PLA supporting array, providing mechanical strength to fully insert the Microneedles into the skin. When inserted into rat skin in vivo, chitosan Microneedles successfully separated from the supporting array and were left within the skin for sustained drug delivery without requiring a transdermal patch. The microneedle penetration depth was approximately 600 mm (i.e. the total length of the microneedle), which is beneficial for targeted delivery of antigens to antigen-presenting cells in the epidermis and dermis. To evaluate the utility of chitosan Microneedles for intradermal vaccination, ovalbumin (OVA; MW ¼ 44.3 kDa) was used as a model antigen. When the OVA-loaded Microneedles were embedded in rat skin in vivo, histological examination showed that the Microneedles gradually degraded and prolonged OVA exposure at the insertion sites for up to 14 days. Compared to traditional intramuscular immunization, rats immunized by a single microneedle dose of OVA showed a significantly higher OVAspecific antibody response which lasted for at least 6 weeks. These results suggest that embeddable chitosan Microneedles are a promising depot for extended delivery of encapsulated antigens to provide sustained immune stimulation and improve immunogenicity.

  • Fully embeddable chitosan Microneedles as a sustained release depot for intradermal vaccination
    Biomaterials, 2013
    Co-Authors: Mei Chin Chen, Kuan Ying Lai, Shih-fang Huang, Ming Hung Ling
    Abstract:

    This study introduces a microneedle transdermal delivery system, composed of embeddable chitosan Microneedles and a poly(l-lactide-co-D,l-lactide) (PLA) supporting array, for complete and sustained delivery of encapsulated antigens to the skin. Chitosan Microneedles were mounted to the top of a strong PLA supporting array, providing mechanical strength to fully insert the Microneedles into the skin. When inserted into rat skin in vivo, chitosan Microneedles successfully separated from the supporting array and were left within the skin for sustained drug delivery without requiring a transdermal patch. The microneedle penetration depth was approximately 600 μm (i.e. the total length of the microneedle), which is beneficial for targeted delivery of antigens to antigen-presenting cells in the epidermis and dermis. To evaluate the utility of chitosan Microneedles for intradermal vaccination, ovalbumin (OVA; MW = 44.3 kDa) was used as a model antigen. When the OVA-loaded Microneedles were embedded in rat skin in vivo, histological examination showed that the Microneedles gradually degraded and prolonged OVA exposure at the insertion sites for up to 14 days. Compared to traditional intramuscular immunization, rats immunized by a single microneedle dose of OVA showed a significantly higher OVA-specific antibody response which lasted for at least 6 weeks. These results suggest that embeddable chitosan Microneedles are a promising depot for extended delivery of encapsulated antigens to provide sustained immune stimulation and improve immunogenicity. © 2013 Elsevier Ltd.