Fortified micronutrient salt formulations

Mucosal pathogens, as exemplified by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human immunodeficiency virus (HIV) and Mycobacterium tuberculosis, lead to substantial morbidity and mortality worldwide and pose serious threats to global health. Mucosal vaccination is crucial to combating mucosal pathogens because it enables the immune system to directly target and neutralize pathogens at their point of entry. Mucosal vaccines need to penetrate the mucus layer, reach the target tissue and activate robust immune responses in the mucosal tissues. Material-based strategies are necessary to meet these requirements. In this Review, we provide an overview of current mucosal vaccines, categorized by administration route, to highlight the importance of material design in overcoming the existing delivery challenges. We discuss the different classes of materials currently being used as …

Science Advances

Nanomaterials offer unique opportunities to engineer immunomodulatory activity. In this work, we report the Toll-like receptor agonist activity of a nanoscale adjuvant zeolitic imidazolate framework–8 (ZIF-8). The accumulation of ZIF-8 in endosomes and the pH-responsive release of its subunits enable selective engagement with endosomal Toll-like receptors, minimizing the risk of off-target activation. The intrinsic adjuvant properties of ZIF-8, along with the efficient delivery and biomimetic presentation of a severe acute respiratory syndrome coronavirus 2 spike protein receptor-binding domain trimer, primed rapid humoral and cell-mediated immunity in a dose-sparing manner. Our study offers insights for next-generation adjuvants that can potentially impact future vaccine development.

Nature Biotechnology

Decentralized manufacture of thermostable mRNA vaccines in a microneedle patch (MNP) format could enhance vaccine access in low-resource communities by eliminating the need for a cold chain and trained healthcare personnel. Here we describe an automated process for printing MNP Coronavirus Disease 2019 (COVID-19) mRNA vaccines in a standalone device. The vaccine ink is composed of lipid nanoparticles loaded with mRNA and a dissolvable polymer blend that was optimized for high bioactivity by screening formulations in vitro. We demonstrate that the resulting MNPs are shelf stable for at least 6 months at room temperature when assessed using a model mRNA construct. Vaccine loading efficiency and microneedle dissolution suggest that efficacious, microgram-scale doses of mRNA encapsulated in lipid nanoparticles could be delivered with a single patch. Immunizations in mice using …

Advanced Functional Materials

Accurate medical recordkeeping is important for personal and public health. Conventional forms of on‐patient medical information, such as medical alert bracelets or finger‐markings, may compromise patient privacy because they are readily visible to other people. Here, the development of an invisible, temporary, and easily deployable on‐patient medical recordkeeping system is reported. Information is stored in unique patterns of spatially distributed near‐infrared (NIR) fluorescent quantum dots (QDs), which are delivered to the skin using dissolvable microneedle arrays. The patterns are invisible to the naked eye but detectable with an infrared camera, which can extract information with >98% accuracy using automated pattern recognition software. By encapsulating NIR QDs in an FDA‐approved biodegradable polymer, biodegradation rates can be tuned so that the encoded medical information can be conveyed …

2020-10-27 Assigned to THE BRIGHAM AND WOMEN'S HOSPITAL, INC. reassignment THE BRIGHAM AND WOMEN'S HOSPITAL, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: ALEXIS, FRANK, FAROKHZAD, OMID C.

bioRxiv

Cancer therapy research is of high interest because of the persistence and mortality of the disease and the side effects of traditional therapeutic methods, while often multimodal treatments are necessary based on the patient’s needs. The development of less invasive modalities for recurring treatment cycles is thus of critical significance. Herein, a light-activatable microparticle system was developed for localized, pulsatile delivery of anticancer drugs with simultaneous thermal ablation, by applying controlled ON-OFF thermal cycles using near-infrared laser irradiation. The system is composed of poly(caprolactone) microparticles of 200 μm size with incorporated molybdenum disulfide (MoS2) nanosheets as the photothermal agent and hydrophilic doxorubicin or hydrophobic violacein, as model drugs. Upon irradiation the nanosheets heat up to ≥50 °C leading to polymer matrix melting and release of the drug. MoS2 nanosheets exhibit high photothermal conversion efficiency and allow for application of low power laser irradiation for the system activation. A Machine Learning algorithm was applied to acquire optimal laser operation conditions; 0.4 W/cm2 laser power at 808 nm, 3-cycle irradiation, for 3 cumulative minutes. In a mouse subcutaneous model of 4T1 triple-negative breast cancer, 25 microparticles were intratumorally administered and after 3-cycle laser treatment the system conferred synergistic phototherapeutic and chemotherapeutic effect. Our on-demand, pulsatile synergistic treatment resulted in increased median survival up to 40 days post start of treatment compared to untreated mice, with complete eradication of the tumors at the …

Nature biomedical engineering

Improvements in ingestible electronics with the capacity to sense physiological and pathophysiological states have transformed the standard of care for patients. Yet, despite advances in device development, significant risks associated with solid, non-flexible gastrointestinal transiting systems remain. Here, we report the design and use of an ingestible, flexible piezoelectric device that senses mechanical deformation within the gastric cavity. We demonstrate the capabilities of the sensor in both in vitro and ex vivo simulated gastric models, quantify its key behaviours in the gastrointestinal tract using computational modelling and validate its functionality in awake and ambulating swine. Our proof-of-concept device may lead to the development of ingestible piezoelectric devices that might safely sense mechanical variations and harvest mechanical energy inside the gastrointestinal tract for the diagnosis and treatment …

Cancer Research

The ability to treat tumors with high efficacy in a local microenvironment, while mitigating the side effects of systemic toxicity is an area of active investigation. Towards this goal, designing a minimally-invasive local therapeutic modality, with a controlled, pulsatile drug release mechanism is an attractive proposition. In this study, a near-infrared (NIR) photo-activatable microparticle was developed for localized, pulsatile delivery of encapsulated anticancer drugs into the tumor with simultaneous thermal ablation, with controlled ON-OFF thermal cycles using NIR laser irradiation. The microparticles were fabricated using a poly(caprolactone) (PCL) matrix, containing 2D molybdenum disulfide (MoS2) nanosheets as the NIR-responsive photothermal agent, and doxorubicin or violacein, as hydrophilic and hydrophobic model anticancer drugs, respectively. Cubic microparticles of 200 µm size were fabricated by casting a …

A method for the systemic delivery of a polypeptide within a subject is provided by creating genetically modified skin cells via topical introduction of a genetically engineered virus which delivers a nucleic acid encoding a therapeutic polypeptide for expression by the skin cells, wherein the expressed therapeutic polypeptide is secreted by the skin cells and is introduced into the circulatory system of the subject.

Microbes and Infection

Chronic wounds are difficult to treat due to the presence of biofilm which prevents wound healing. Pseudomonas aeruginosa is one of the most common pathogens found in chronic wounds and conventional treatment strategies have been ineffective in the eradication of its biofilm, without harming the surrounding healthy tissue at the same time. Here, we introduced an innovative approach applying the probiotic product Bio-K+ (containing three lactobacilli) topically as an antimicrobial and antibiofilm agent. We identified lactic acid as the main active component. While antibiotics and antiseptics such as silver-ions only demonstrated limited efficacy, Bio-K+ was able to completely eradicate mature P. aeruginosa biofilms established in an in-vitro and ex-vivo human skin model. Furthermore, it demonstrated biocompatibility in the co-culture with human dermal fibroblasts and accelerated the migration of fibroblasts in a …

Disclosed are compositions that stabilize (eg, thermo-stabilize) biological agents, such as mRNA. Also disclosed are methods of administering and using said compositions.

Residence devices for long term delivery of therapeutic compounds and/or for sensing one or more relevant parameters in vivo are disclosed. In one embodiment, a residence device may include a plurality of links interconnected by a corresponding plurality of flexible hinges to permit the residence device to be deformed into a contracted configuration and subsequently permitted to return to an expanded configuration once positioned in a desired location, such as the stomach, of a subject. In some instances, at least a portion of the interconnected links may include a first link segment, a second link segment, and a coupling that selectively connects the first link segment to the second link segment. The coupling may be configured to weaken or decouple a connection between the first link segment and the second link segment when exposed to a temperature greater than a threshold temperature to selectively weaken …

TheScienceBreaker

Vitamin A deficiency impacts millions globally. Directly adding it to foods is problematic due to its sensitivity to light and heat. We've created an edible microparticle ensuring safe vitamin A delivery. These microparticles are stable and offer high absorption rates, presenting a groundbreaking solution to combat vitamin A deficiency and degradation globally.

Drug delivery articles, resident articles, and retrieval systems eg, for gram-level dosing, are generally provided. In some embodiments, the articles are configured for transesophageal administration, transesophageal retrieval, and/or gastric retention to/in a subject. In certain embodiments, the article includes dimensions configured for transesophageal administration with a gastric resident system. In some cases, the article may be configured to control drug release eg, with zero-order drug kinetics with no potential for burst release for weeks to months. In some embodiments, the articles described herein comprise biocompatible materials and/or are safe for gastric retention. In certain embodiments, the article includes dimensions configured for transesophageal retrieval. In some cases, the articles described herein may comprise relatively large doses of drug (eg, greater than or equal to 1 gram).

Vaccines provide substantial safety against infectious diseases, saving millions of lives each year. The recent COVID-19 pandemic highlighted the importance of vaccination in providing mass-scale immunization against outbreaks. However, the delivery of vaccines imposes a unique set of challenges due to their large molecular size and low room temperature stability. Advanced biomaterials and delivery systems such as micro- and nanoscale carriers are becoming critical components for successful vaccine developments. In this review, we provide an updated overview of recent advances in the development of micro- and nano-scale carriers for controlled delivery of vaccines, focusing on carriers compatible with nucleic acid-based vaccines and therapeutics that emerged amid the recent pandemic. We start by detailing nanoscale delivery systems, focusing on nanoparticles, then move on to microscale systems …

2018-01-30 Assigned to NATIONAL INSTITUTES OF HEALTH (NIH), US DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), US GOVERNMENT reassignment NATIONAL INSTITUTES OF HEALTH (NIH), US DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), US GOVERNMENT CONFIRMATORY LICENSE (SEE DOCUMENT FOR DETAILS). Assignors: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

Angewandte Chemie

DNA biotechnology offers intriguing opportunities for amplification‐based sensitive detection. However, spatiotemporally‐controlled manipulation of signal amplification for in situ imaging of the tumor microenvironment remains an outstanding challenge. Here, we demonstrate a DNA‐based strategy that can spatial‐selectively amplify the acidic signal in the extracellular milieu of the tumor to achieve specific imaging with improved sensitivity. The strategy, termed mild acidosis‐targeted amplification (MAT‐amp), leverages the specific acidic microenvironment to engineer tumor cells with artificial DNA receptors through a pH (low) insertion peptide, which permits controlled recruitment of fluorescent amplifiers via a hybridization chain reaction. The acidosis‐responsive amplification cascade enables significant fluorescence enhancement in tumors with a reduced background signal in normal tissues, leading to …