Project description:A wearable adhesive skin patch for transdermal drug delivery is developed with bendable microneedles, dry adhesive and triboelectric energy harvester (TEH). The bendable microneedle array can overcome the needle breakage issue. The dry adhesive can realize a conformal attachment. The TEH can generate power when attached on flat skin or joint to power active components to be integrated in the future.
Project description:Dissolving microneedles (DMNs) are polymeric, microscopic needles that deliver encapsulated drugs in a minimally invasive manner. Currently, DMN arrays are superimposed onto patches that facilitate their insertion into skin. However, due to wide variations in skin elasticity and the amount of hair on the skin, the arrays fabricated on the patch are often not completely inserted and large amount of loaded materials are not delivered. Here, we report "Microlancer", a novel micropillar based system by which patients can self-administer DMNs and which would also be capable of achieving 97 ± 2% delivery efficiency of the loaded drugs regardless of skin type or the amount of hair on the skin in less than a second.
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.
Project description:Patient adherence to chronic therapies can be suboptimal, leading to poor therapeutic outcomes. Dosage forms that enable reduction in dosing frequency stand to improve patient adherence. Variation in gastrointestinal transit time, inter-individual differences in gastrointestinal physiology and differences in physicochemical properties of drugs represent challenges to the development of such systems. To this end, a small intestine-targeted drug delivery system is developed, where prolonged gastrointestinal retention and sustained release are achieved through tissue adhesion of drug pills mediated by an essential intestinal enzyme catalase. Here proof-of-concept pharmacokinetics is demonstrated in the swine model for two drugs, hydrophilic amoxicillin and hydrophobic levodopa. It is anticipated that this system can be applicable for many drugs with a diverse of physicochemical characteristics.
Project description:The pain and fear caused by direct local injection of anesthetic or the poor experience with surface anesthetic cream increase the difficulty of clinical treatment for oral diseases. To address this problem, a hyaluronic acid microneedle patch (Li-HAMNs) that consists of fast-dissolving lidocaine hydrochloride (LDC)-loaded tips and a wet-adhesive backing layer made of polyvinyl alcohol (PVA)/carboxymethylcellulose sodium (CMC-Na) was fabricated to explore its potential use in dental topical anesthesia. Li-HAMNs could puncture the stratum corneum with an insertion depth of about 279 μm in the isolated porcine oral mucosal. The fast-dissolving tips could release LDC to improve the patients' convenience and compliance. Importantly, the backing layer, which has good adhesion ability and water-absorbing properties, could surmount the contraction and extension of oral masticatory muscles and the saliva scour. In the tail flick test, the topical anesthesia efficacy of the Li-HAMNs group was much better than clinical lidocaine cream (EMLA cream, LDC, 1.2 mg) in spite of a relatively lower LDC dose with Li-HAMNs (LDC, 0.5 mg). It is believed that the proposed adhesive microneedle patch could enhance transmucosal delivery of anesthetics and thus open a new chapter in the painless treatment of oral diseases.
Project description:Micromotors have demonstrated values in drug delivery, and recent attempts focus on developing effective approaches to generate functional micromotors to improve this area. Here, with the integration of microfluidic droplet printing and wettability-induced drawing photolithography, we present an innovative spatiotemporal serial multistep dip-printing strategy to generate novel independent microneedle motors (IMNMs) for orally delivering macromolecular drugs. As the strategy combines the advantages of the hydrophilic wettability, extension effects, and capillary effects, the IMNMs with an oblate basement and a needle-shaped head or a core-shell structured multicomponent head can be created by simply printing pregel droplets layer by layer, following with simultaneous wiredrawing and solidification. Owing to the polarized magnetic particles in the bottom basement and the rapidly dissolvable polymers as the middle basement, the resultant IMNMs can respond to magnetic fields, move to desired places under a magnet, penetrate tissue-like substrates, induce head-basement separation, and leave only the needles for cargo release. Based on these features, we have demonstrated that these IMNMs can deliver insulin via intestinal tracts to realize effective blood glucose control of diabetic rabbit models. These results indicate the practical values and bright future of the dip-printing stratagem and these IMNMs in clinical applications.
Project description:Microneedles (MNs) offer a rapid method of transdermal drug delivery through penetration of the stratum corneum. However, commercial translation has been limited by fabrication techniques unique to each drug. Herein, a broadly applicable platform is explored by drug-loading via swelling effect of a hydrogel MN patch. A range of small molecule hydrophilic, hydrophobic, and biomacromolecule therapeutics demonstrate successful loading and burst release from hydrogel MNs fabricated from methacrylated hyaluronic acid (MeHA). The post-fabrication drug loading process allows MeHA MN patches with drug loadings of 10 ?g?cm-2. Additional post-fabrication processes are explored with dendrimer bioadhesives that increase work of adhesion, ensuring stable fixation on skin, and allow for additional drug loading strategies.
Project description:Insulin and other injectable biologic drugs have transformed the treatment of patients suffering from diabetes1,2, yet patients and healthcare providers often prefer to use and prescribe less effective orally dosed medications3-5. Compared with subcutaneously administered drugs, oral formulations create less patient discomfort4, show greater chemical stability at high temperatures6, and do not generate biohazardous needle waste7. An oral dosage form for biologic medications is ideal; however, macromolecule drugs are not readily absorbed into the bloodstream through the gastrointestinal tract8. We developed an ingestible capsule, termed the luminal unfolding microneedle injector, which allows for the oral delivery of biologic drugs by rapidly propelling dissolvable drug-loaded microneedles into intestinal tissue using a set of unfolding arms. During ex vivo human and in vivo swine studies, the device consistently delivered the microneedles to the tissue without causing complete thickness perforations. Using insulin as a model drug, we showed that, when actuated, the luminal unfolding microneedle injector provided a faster pharmacokinetic uptake profile and a systemic uptake >10% of that of a subcutaneous injection over a 4-h sampling period. With the ability to load a multitude of microneedle formulations, the device can serve as a platform to orally deliver therapeutic doses of macromolecule drugs.
Project description:Self-nanoemulsifying drug delivery system (SNEDDS) has emerged as a promising platform to improve oral absorption of drugs with poor solubility and low permeability. However, large polarity molecules with insufficient lipid solubility, such as paclitaxel (PTX), would suffer from inferior formulation of SNEDDS due to poor compatibility. Herein, phospholipid-drug complex (PLDC) and SNEDDS were integrated into one system to facilitate oral delivery of PTX. First, PTX was formulated into PLDC in response to its inferior physicochemical properties. Then, the prepared PLDC was further formulated into SNEDDS by integrating these two drug delivery technologies into one system (PLDC-SNEDDS). After PLDC-SNEDDS dispersed in aqueous medium, nanoemulsion was formed immediately with an average particle size of ?30?nm. Furthermore, the nanomulsion of PLDC-SNEDDS showed good colloidal stability in both HCl solution (0.1?mol/l, pH 1.0) and phosphate buffer solution (PBS, pH 6.8). In vivo, PTX-PLDC-SNEDDS showed distinct advantages in terms of oral absorption efficiency, with a 3.42-fold and 2.13-fold higher bioavailability than PTX-PLDC and PTX solution, respectively. Our results suggest that the integration of PLDC into SNEDDS could be utilized to facilitate the oral delivery of hydrophobic drugs with large polarity.
Project description:The use of microneedles has facilitated the painless localized delivery of drugs across the skin. However, their efficacy has been limited by slow diffusion of molecules and often requires external triggers. Herein, an autonomous and degradable, active microneedle delivery platform is introduced, employing magnesium microparticles loaded within the microneedle patch, as the built-in engine for deeper and faster intradermal payload delivery. The magnesium particles react with the interstitial fluid, leading to an explosive-like rapid production of H2 bubbles, providing the necessary force to breach dermal barriers and enhance payload delivery. The release kinetics of active microneedles is evaluated in vitro by measuring the amount of IgG antibody (as a model drug) that passed through phantom tissue and a pigskin barrier. In vivo experiments using a B16F10 mouse melanoma model demonstrate that the active delivery of anti-CTLA-4 (a checkpoint inhibitor drug) results in greatly enhanced immune response and significantly longer survival. Moreover, spatially resolved zones of active and passive microneedles allow a combinatorial rapid burst response along with slow, sustained release, respectively. Such versatile and effective autonomous dynamic microneedle delivery technology offers considerable promise for a wide range of therapeutic applications, toward a greatly enhanced outcome, convenience, and cost.