Project description:Triptorelin is a first-line drug for assisted reproductive technology (ART), but the low bioavailability and frequent subcutaneous injection of triptorelin impair the quality of life of women preparing to become pregnant. We report silk fibroin (SF)-based microneedles (MNs) for transdermal delivery of triptorelin-loaded nanoparticles (NPs) to improve bioavailability and achieve safe and efficacious self-administration of triptorelin. Triptorelin was mixed into an aqueous solution of SF with shear force to prepare NPs to control the release and avoid the degradation of triptorelin by enzymes in the skin. Two-step pouring and centrifugation were employed to prepare nanoparticles-encapsulated polymeric microneedles (NPs-MNs). An increased β-sheet content in the conformation ensured that NPs-MNs had good mechanical properties to pierce the stratum corneum. Transdermal release of triptorelin from NPs-MNs was increased to ∼65%. The NPs-MNs exhibited a prolonged drug half-life and increased relative bioavailability after administration to rats. Surging levels of luteinizing hormone and estradiol in plasma and their subsequent prolonged downregulation indicate the potential therapeutic role of NPs-MNs in ART regimens. The triptorelin-loaded NPs-MNs developed in this study may reduce the physical and psychological burden of pregnant women using ART regimens.
Project description:Social VR enables people to interact over distance with others in real-time. It allows remote people, typically represented as avatars, to communicate and perform activities together in a shared virtual environment, extending the capabilities of traditional social platforms like Facebook and Netflix. This paper explores the benefits and drawbacks provided by a lightweight and low-cost Social VR platform (SocialVR), in which users are captured by several cameras and reconstructed in real-time. In particular, the paper contributes with (1) the design and evaluation of an experimental protocol for Social VR experiences; (2) the report of a production workflow for this new type of media experiences; and (3) the results of experiments with both end-users (N = 15 pairs) and professionals (N = 22 companies) to evaluate the potential of the SocialVR platform. Results from the questionnaires and semi-structured interviews show that end-users rated positively towards the experiences provided by the SocialVR platform, which enabled them to sense emotions and communicate effortlessly. End-users perceived the photo-realistic experience of SocialVR similar to face-to-face scenarios and appreciated this new creative medium. From a commercial perspective, professionals confirmed the potential of this communication medium and encourage further research for the adoption of the platform in the commercial landscape.Supplementary informationThe online version contains supplementary material available at 10.1007/s10055-022-00651-5.
Project description:BackgroundMinimally invasive skin sampling is used in various fields. In this study, we examined whether it was possible to obtain skin specimens using biocompatible microneedles composed of sodium hyaluronate and performed transcriptome analysis.Materials and methodsThirty-three subjects with different skin conditions, such as skin aging, skin hydration, skin pigmentation, oily skin and sensitive skin, were recruited. Skin types were evaluated based on age, non-invasive measurement devices, 10% lactic acid stinging test and visual assessment; the skin specimens were sampled from the face using microneedles. Total RNA was extracted, and microarray was performed. Correlations between various biomarkers and skin condition parameters were analysed.ResultsSeveral skin-type biomarkers are correlated with age, non-invasive device measurements, LAST score and visual assessment of acne lesions. Representatively, COL1A1 (Collagen type 1 alpha 1 chain), FN1 (Fibronectin 1) and PINK1 (PTEN-induced putative kinase protein 1) for skin aging, FLG (Filaggrin), KLF4 (Kruppel-like factor 4) and LOR (Loricrin) for skin hydration, GPNMB (Glycoprotein non-metastatic melanoma protein B), MLANA (Melan-A) and TYR (Tyrosinase) for skin pigmentation, IGF1 (insulin-like growth factor-1), MPZL3 (Myelin protein zero like 3) and AQP3 (Aquaporin 3) for oily skin and PGF (placental growth factor), CYR61 (cysteine-rich angiogenic inducer 61), RBP4 (retinol-binding protein 4), TAC1 (Tachykinin precursor 1), CAMP (Cathelicidin antimicrobial peptide), MMP9 (Matrix metallopeptidase 9), MMP3, MMP12 and CCR1 (C-C motif chemokine receptor 1) for sensitive skin.ConclusionMicroneedle skin sampling is a new and minimally invasive option for transcriptome analysis of human skin and can be applied for diagnosis and treatment efficacy evaluation, as well as skin type classification.
Project description: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.
Project description:Hollow microneedles are an emerging technology for delivering drugs and therapeutics, such as vaccines and insulin, into the skin. Although the benefits of intradermal drug delivery have been known for decades, our understanding of fluid absorption by skin tissue has been limited due to the difficulties in imaging a highly scattering biological material such as skin. Here, we report the first real-time imaging of skin tissue at the microscale during intradermal injections through hollow microneedles, using optical coherence tomography. We show that skin tissue behaves like a deformable porous medium and absorbs fluid by locally expanding rather than rupturing to form a single fluid filled cavity. We measure the strain distribution in a cross section of the tissue to quantify local tissue deformation, and find that the amount of volumetric expansion of the tissue corresponds closely to the volume of fluid injected. Mechanically restricting tissue expansion limits fluid absorption into the tissue. Our experimental findings can provide insights to optimize the delivery of drugs into skin for different therapeutic applications, and to better model fluid flow into biological tissue.
Project description:Human papilloma virus-like particles (HPV VLP) serve as the basis of the current licensed vaccines for HPV. We have previously shown that encapsidation of DNA expressing the model antigen M/M2 from respiratory syncytial virus (RSV) in HPV pseudovirions (PsV) is immunogenic when delivered intravaginally. Because the HPV capsids confer tropism for basal epithelium, they represent attractive carriers for vaccination targeted to the skin using microneedles. In this study we asked: 1) whether HPV16 VLP administered by microneedles could induce protective immune responses to HPV16 and 2) whether HPV16 PsV-encapsidated plasmids delivered by microneedles could elicit immune responses to both HPV and the antigen delivered by the transgene. Mice immunized with HPV16 VLP coated microneedles generated robust neutralizing antibody responses and were protected from HPV16 challenge. Microneedle arrays coated with HPV16-M/M2 or HPV16-F protein (genes of RSV) were then tested and dose-dependent HPV and F-specific antibody responses were detected post-immunization, and M/M2-specific T-cell responses were detected post RSV challenge, respectively. HPV16 PsV-F immunized mice were fully protected from challenge with HPV16 PsV and had reduced RSV viral load in lung and nose upon intranasal RSV challenge. In summary, HPV16 PsV-encapsidated DNA delivered by microneedles induced neutralizing antibody responses against HPV and primed for antibody and T-cell responses to RSV antigens encoded by the encapsidated plasmids. Although the immunogenicity of the DNA component was just above the dose response threshold, the HPV-specific immunity was robust. Taken together, these data suggest microneedle delivery of lyophilized HPV PsV could provide a practical, thermostable combined vaccine approach that could be developed for clinical evaluation.
Project description:Live-attenuated oral rotavirus (RV) vaccines have lower efficacy in low income countries, and additionally are associated with a rare but severe adverse event, intussusception. We have been pursuing the development of an inactivated rotavirus vaccine (IRV) using the human rotavirus strain CDC-9 (G1P[8]) through parenteral immunization and previously demonstrated dose sparing and enhanced immunogenicity of intradermal (ID) unadjuvanted IRV using a coated microneedle patch in comparison with intramuscular (IM) administration in mice. The aim of this study was to evaluate the immune response and protection against RV infection and diarrhea conferred by the administration of the ID unadjuvanted IRV using the microneedle device MicronJet600® in neonatal gnotobiotic (Gn) piglets challenged with virulent Wa G1P[8] human RV. Three doses of 5 μg IRV when administered intradermally and 5 μg IRV formulated with aluminum hydroxide [Al(OH)3] when administered intramuscularly induced comparable rotavirus-specific antibody titers of IgA, IgG, IgG avidity index and neutralizing activity in sera of neonatal piglets. Both IRV vaccination regimens protected against RV antigen shedding in stools, and reduced the cumulative diarrhea scores in the piglets. This study demonstrated that the ID and IM administrations of IRV are immunogenic and protective against RV-induced diarrhea in neonatal piglets. Our findings highlight the potential value of an adjuvant sparing effect of the IRV ID delivery route.
Project description:IntroductionManaging large chronic wounds presents significant challenges because of inadequate donor sites, infection, and lack of structural support from dermal substitutes. Hydrogels are extensively used in various forms to promote chronic wound healing and provide a three-dimensional spatial structure, through growth factors or cell transport.ObjectivesWe present a novel multicenter regenerative model that is capable of regenerating and merging simultaneously to form a complete layer of skin. This method significantly reduces wound healing time compared to the traditional centripetal healing model. We believe that our model can improve clinical outcomes and pave the way for further research into regenerative medicine.MethodsWe prepared a novel multi-island double-layer microneedle (MDMN) using gelatin-methacryloylchitosan (GelMA-CS). The MDMN was loaded with keratinocytes (KCs) and dermal fibroblasts (FBs). Our aim in this study was to explore the therapeutic potential of MDMN in a total skin excision model.ResultsThe MDMN model replicated the layered structure of full-thickness skin and facilitated tissue regeneration and healing via dual omni-bearing. Multi-island regeneration centres accomplished horizontal multicentric regeneration, while epidermal and dermal cells migrated synchronously from each location. This produced a healing area approximately 4.7 times greater than that of the conventional scratch tests. The MDMN model exhibited excellent antibacterial properties, attributed to the chitosan layer. During wound healing in diabetic mice, the MDMN achieved earlier epidermal coverage and faster wound healing through multi-island regeneration centres and the omnidirectional regeneration mode. The MDMN group displayed an accelerated wound healing rate upon arrival at the destination (0.96 % ± 0.58 % vs. 4.61 % ± 0.32 %). Additionally, the MDMN group exhibited superior vascularization and orderly collagen deposition.ConclusionThe present study presents a novel skin regeneration model using microneedles as carriers of autologous keratinocytes and dermal fibroblasts, which allows for omni-directional, multi-center, and full-thickness skin regeneration.
Project description:Polymer-based microneedles have drawn much attention in transdermal drug delivery resulting from their flexibility and biocompatibility. Traditional fabrication approaches are usually time-consuming and expensive. In this study, we developed a new double drawing lithography technology to make biocompatible SU-8 microneedles for transdermal drug delivery applications. These microneedles are strong enough to stand force from both vertical direction and planar direction during penetration. They can be used to penetrate into the skin easily and deliver drugs to the tissues under it. By controlling the delivery speed lower than 2 μl/min per single microneedle, the delivery rate can be as high as 71%.
Project description:Microneedle (MN)-based diagnostic devices can efficiently access skin interstitial fluid (ISF) for accurate and minimally invasive detection of health-related biomarkers. This work reports a biomarker (i.e., glucose or alcohol) monitoring MN device that is composed of swellable MNs and electrochemical test strip. This device is constructed by adhering MN patch on the electrochemical strips using the chitosan as the connecting layer. The MNs penetrate the skin for extraction of ISF that flows to the backing layer of MNs and is analyzed by the test strip. In the in vitro skin models, this device accurately detects the glucose from 0 mM to 12 mM and alcohol from 0 mM to 20 mM. In vivo experiment shows this MN device is capable of minimally invasive sampling of ISF and analysis of glucose levels to determine the glycemic status of mice.