Effect of Surface Interactions on Microsphere Loading in Dissolving Microneedle Patches.
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ABSTRACT:
SUBMITTER: Jang D
PROVIDER: S-EPMC9264316 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Influenza prophylaxis would benefit from a vaccination method enabling simplified logistics and improved immunogenicity without the dangers posed by hypodermic needles. Here we introduce dissolving microneedle patches for influenza vaccination using a simple patch-based system that targets delivery to skin's antigen-presenting cells. Microneedles were fabricated using a biocompatible polymer encapsulating inactivated influenza virus vaccine for insertion and dissolution in the skin within minutes. Microneedle vaccination generated robust antibody and cellular immune responses in mice that provided complete protection against lethal challenge. Compared to conventional intramuscular injection, microneedle vaccination resulted in more efficient lung virus clearance and enhanced cellular recall responses after challenge. These results suggest that dissolving microneedle patches can provide a new technology for simpler and safer vaccination with improved immunogenicity that could facilitate increased vaccination coverage.
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Project description:A multifunctional system comprised of hyaluronic acid microneedles was developed as an effective transdermal delivery platform for rapid local delivery. The microneedles can regulate the filling amount on the tip, by controlling the concentration of hyaluronic acid solution. Ultrasonication induces dissolution of the HA microneedles via vibration of acoustic pressure, and AC iontophoresis improves the electrostatic force-driven diffusion of HA ions and rhodamine B. The effect of ultrasound on rhodamine release was analyzed in vitro using a gelatin hydrogel. The frequency and voltage dependence of the AC on the ion induction transfer was also evaluated experimentally. The results showed that the permeability of the material acts as a key material property. The delivery system based on ultrasonication and iontophoresis in microneedles increases permeation, thus resulting in shorter initial delivery time than that required by delivery systems based on passive or ultrasonication alone. This study highlights the significance of the combination between ultrasonic waves and iontophoresis for improving the efficiency of the microneedles, by shortening the reaction duration. We anticipate that this system can be extended to macromolecular and dependence delivery, based on drug response time.
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Project description:Chronic inflammatory skin diseases (CISDs) negatively impact a large number of patients. Injection of triamcinolone acetonide (TA), an anti-inflammatory steroid drug, directly into the dermis of diseased skin using needle-syringe systems is a long-established procedure for treating recalcitrant lichenified lesions of CISDs, referred to as TA intralesional injection (TAILI). However, TAILI causes severe pain, causing patients to be stressed and reluctant to undergo treatment. Furthermore, the practitioner dependency on the amount and depth of the injected TA makes it difficult to predict the prognosis. Here, candle flame ("candlelit")-shaped TA-loaded dissolving microneedles (Candlelit-DMN) are designed and fabricated out of biocompatible and biodegradable molecules. Candlelit-DMN distributes TA evenly across human skin tissue. Conjoined with the applicator, Candlelit-DMN is efficiently inserted into human skin in a standardized manner, enabling TA to be delivered within the target layer. In an in vivo skin inflammation mouse model, Candlelit-DMN inserted with the applicator effectively alleviates inflammation by suppressing inflammatory cell infiltration and cytokine gene expression, to the same extent as TAILI. This Candlelit-DMN with the applicator arouses the interest of dermatologists, who prefer it to the current TAILI procedure.
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Project description:Prophylactic vaccines capable of preventing human papillomavirus (HPV) infections are still inaccessible to a vast majority of the global population due to their high cost and challenges related to multiple administrations performed in a medical setting. In an effort to improve distribution and administration, we have developed dissolvable microneedles loaded with a thermally stable HPV vaccine candidate consisting of Qβ virus-like particles (VLPs) displaying a highly conserved epitope from the L2 protein of HPV (Qβ-HPV). Polymeric microneedle delivery of Qβ-HPV produces similar amounts of anti-HPV16 L2 IgG antibodies compared to traditional subcutaneous injection while delivering a much smaller amount of intradermal dose. However, a dose sparing effect was found. Furthermore, immunization yielded neutralizing antibody responses in a HPV pseudovirus assay. The vaccine candidate was confirmed to be stable at room temperature after storage for several months, potentially mitigating many of the challenges associated with cold-chain distribution. The ease of self-administration and minimal invasiveness of such microneedle patch vaccines may enable wide-scale distribution of the HPV vaccine and lead to higher patient compliance. The Qβ VLP and its delivery technology is a plug-and-play system that could serve as a universal platform with a broad range of applications. Qβ VLPs may be stockpiled for conjugation to a wide range of epitopes, which are then packaged and delivered directly to the patient via noninvasive microneedle patches. Such a system paves the way for rapid distribution and self-administration of vaccines.
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Project description:The skin is an attractive tissue target for vaccination, as it is readily accessible and contains a dense population of antigen-presenting and immune-accessory cells. Microneedle arrays (MNAs) are emerging as an effective tool for in situ engineering of the cutaneous microenvironment to enable diverse immunization strategies. Here, we present novel dissolving undercut MNAs and demonstrate their application for effective multicomponent cutaneous vaccination. The MNAs are composed of micron-scale needles featuring pyramidal heads supported by undercut stem regions with filleted bases to ensure successful skin penetration and retention during application. Prior efforts to fabricate dissolving undercut microstructures were limited and required complex and lengthy processing and assembly steps. In the current study, we strategically combine three-dimensional (3D) laser lithography, an emerging micro-additive manufacturing method with unique geometric capabilities and nanoscale resolution, and micromolding with favorable materials. This approach enables reproducible production of dissolving MNAs with undercut microneedles that can be tip-loaded with multiple biocargos, such as antigen (ovalbumin) and adjuvant (Poly(I:C)). The resulting MNAs fulfill the geometric (sharp tips and smooth edges) and mechanical-strength requirements for failure-free penetration of human and murine skin to simultaneously deliver multicomponent (antigen plus adjuvant) vaccines to the same cutaneous microenvironment. Cutaneous vaccination of mice using these MNAs induces more potent antigen-specific cellular and humoral immune responses than those elicited by traditional intramuscular injection. Together, the unique geometric features of these undercut MNAs and the associated manufacturing strategy, which is compatible with diverse drugs and biologics, could enable a broad range of non-cutaneous and cutaneous drug delivery applications, including multicomponent vaccination.
| S-EPMC8237702 | biostudies-literature
Project description:Clinical medicine and public health would benefit from simplified acquisition of biological samples from patients that can be easily obtained at point of care, in the field, and by patients themselves. Microneedle patches are designed to serve this need by collecting dermal interstitial fluid containing biomarkers without the dangers, pain, or expertise needed to collect blood. This study presents novel methods to collect biomarker analytes from microneedle patches for analysis by integration into conventional analytical laboratory microtubes and microplates. Microneedle patches were made out of cross-linked hydrogel composed of poly(methyl vinyl ether-alt-maleic acid) and poly(ethylene glycol) prepared by micromolding. Microneedle patches were shown to swell with water up to 50-fold in volume, depending on degree of polymer cross-linking, and to collect interstitial fluid from the skin of rats. To collect analytes from microneedle patches, the patches were mounted within the cap of microcentrifuge tubes or formed the top of V-bottom multiwell microplates, and fluid was collected in the bottom of the tubes under gentle centrifugation. In another method, microneedle patches were attached to form the bottom of multiwell microplates, thereby enabling in situ analysis. The simplicity of biological sample acquisition using microneedle patches coupled with the simplicity of analyte collection from microneedles patches integrated into conventional analytical equipment could broaden the reach of future screening, diagnosis, and monitoring of biomarkers in healthcare and environmental/workplace settings.
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Project description:Levothyroxine (LT-4) sodium has shown variable bioavailability following oral administration. This can be assigned to the significant influence of gastrointestinal conditions, food and drugs administered concomitantly on the rate and extent of absorption from the gastrointestinal tract. Thus, the aim of this research study was to establish an efficient transdermal delivery system of LT-4 sodium via the application of hyaluronic acid dissolving microneedles. Microneedles-based drug delivery system consists of sharp-tip needles that puncture the top layers of the skin in a minimally invasive manner to create physical channels through which therapeutic molecules can easily diffuse into/across the skin. Hyaluronic acid polymer at different ratios (5-60 %) was used to prepare microneedle arrays (100 needles per array) using a micromoulding technique. Characterisation tests were carried out to select the optimum formulation. F11 formula containing 50% w/v hyaluronic acid and 1% v/v Tween 80 formula showed an appropriate needle shape with dimensions of 432 ± 6.4 μm in height and a tip diameter of 9.8 ± 1.3 μm. The microneedle arrays demonstrated a suitable mechanical strength after applying a force of 32 N per array and an excellent insertion ability both in Parafilm M® and human skin. The in vivo dissolution of microneedles was started rapidly within 5 minutes following the insertion in the skin and completed at 1 hour. Ex vivo permeation study using human skin has shown a significant improvement in LT-4 sodium delivery across the skin compared to control preparations (drug solution and microneedle free film). The microneedle array F11 has significantly (P ≤ 0.05) increased LT-4 sodium permeation through the skin (cumulative permeated amount of 32 ± 2 μg/cm2) in comparison to the control solution (cumulative permeated amount of 0.7 ± 0.07 μg/cm2) and the microneedle free film (cumulative permeated amount of 0.1 ± 0.02 μg/cm2) over 7 hours. The findings from the irritation test revealed that mild erythema was produced from the application of microneedle arrays which disappeared within 24 hours. Accordingly, dissolving hyaluronic acid microneedles could be a feasible and effective approach to delivering LT-4 sodium transdermally without causing significant skin damage.
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Project description:Glutathione is a natural anti-aging substance that prevents the oxidation of protein thiols from reactive oxygen species. In the pharmaceutical industry, reduced glutathione (GSH) has been widely used for skin whitening due to its ability to inhibit tyrosinase. However, its poor permeability and foul odor limit its use in skin applications. Herein, we report a GSH-loaded dissolving microneedle (MN) patch prepared with hyaluronic acid (HA) that enables enhanced permeation across the skin and reduces the foul odor of GSH. HA was selected to prepare odorless GSH solutions and used for MN fabrications as a carrier of GSH. GSH-loaded MN (GSH-MN) arrays prepared from MN-forming solution containing up to 10% GSH showed good pattern uniformity and appropriate mechanical properties for insertion into the skin. The GSH-MNs with a loading capacity of 17.4% dissolve within 10 min following insertion into porcine skin and release the loaded GSH without being oxidized. This new approach combines functional biopolymers to reduce the characteristic GSH odor and advanced transdermal delivery based on MN technology to enhance skin permeation without pain. We believe this technique could expand the application of GSH in many cosmeceutical fields.
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Project description:Despite vaccination representing one of the greatest advances of modern preventative medicine, there remain significant challenges in vaccine distribution, delivery and compliance. Dissolvable microarray patches or dissolving microneedles (DMN) have been proposed as an innovative vaccine delivery platform that could potentially revolutionize vaccine delivery and circumvent many of the challenges faced with current vaccine strategies. DMN, due to their ease of use, lack of elicitation of pain response, self-disabling nature and ease of transport and distribution, offer an attractive delivery option for vaccines. Additionally, as DMN inherently targets the uppermost skin layers, they facilitate improved vaccine efficacy, due to direct targeting of skin antigen-presenting cells. A plethora of publications have demonstrated the efficacy of DMN vaccination for a range of vaccines, with influenza receiving particular attention. However, before the viable adoption of DMN for vaccination purposes in a clinical setting, a number of fundamental questions must be addressed. Accordingly, this review begins by introducing some of the key barriers faced by current vaccination approaches and how DMN can overcome these challenges. We introduce some of the recent advances in the field of DMN technology, highlighting the potential impact DMN could have, particularly in countries of the developing world. We conclude by reflecting on some of the key questions that remain unanswered and which warrant further investigation before DMNs can be utilized in clinical settings.
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Project description:The skin is a very suitable organ for the induction of immune responses to vaccine antigens. Antigen delivery systems to the skin by needle and syringe directly deposit the antigen into the epidermal-dermal compartment, one of the most immunocompetent sites due to the presence of professional antigen-presenting cells aimed at the induction of antigen-specific T cells. In this study, we analyzed the amount of ovalbumin as an antigen delivered to the skin by a microneedle. When ovalbumin protein as an antigen was delivered to the skin of mice using a dissolving microneedle, it induced an immune response through the enhanced proliferation and cytokines production by the splenocytes and lymph nodes. Also, it effectively increased the ovalbumin-specific CD8+ T cell and CD4+ T cell population and induced an ovalbumin-specific CTL response against the graft of ovalbumin-expressing EG7 tumor cells in the immunized mice. Also, we identified the inhibition of tumor growth and prevention of tumor formation in the context of the therapeutic and prophylactic vaccine, respectively through EG-7 tumor mouse model. Finally, these data show the potential of patches as attractive antigen delivery vehicles.
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