Gastrointestinal-based drug delivery is considered the preferred mode of drug administration owing to its convenience for patients, which improves adherence. However, unique characteristics of the ...gastrointestinal tract (such as the digestive environment and constraints on transport across the gastrointestinal mucosa) limit the absorption of drugs. As a result, many medications, in particular biologics, still exist only or predominantly in injectable form. In this Review, we examine the fundamentals of gastrointestinal drug delivery to inform clinicians and pharmaceutical scientists. We discuss general principles, including the challenges that need to be overcome for successful drug formulation, and describe the unique features to consider for each gastrointestinal compartment when designing drug formulations for topical and systemic applications. We then discuss emerging technologies that seek to address remaining obstacles to successful gastrointestinal-based drug delivery.
Bioplastics for a circular economy Rosenboom, Jan-Georg; Langer, Robert; Traverso, Giovanni
Nature reviews. Materials,
02/2022, Letnik:
7, Številka:
2
Journal Article
Recenzirano
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Bioplastics - typically plastics manufactured from bio-based polymers - stand to contribute to more sustainable commercial plastic life cycles as part of a circular economy, in which virgin polymers ...are made from renewable or recycled raw materials. Carbon-neutral energy is used for production and products are reused or recycled at their end of life (EOL). In this Review, we assess the advantages and challenges of bioplastics in transitioning towards a circular economy. Compared with fossil-based plastics, bio-based plastics can have a lower carbon footprint and exhibit advantageous materials properties; moreover, they can be compatible with existing recycling streams and some offer biodegradation as an EOL scenario if performed in controlled or predictable environments. However, these benefits can have trade-offs, including negative agricultural impacts, competition with food production, unclear EOL management and higher costs. Emerging chemical and biological methods can enable the 'upcycling' of increasing volumes of heterogeneous plastic and bioplastic waste into higher-quality materials. To guide converters and consumers in their purchasing choices, existing (bio)plastic identification standards and life cycle assessment guidelines need revision and homogenization. Furthermore, clear regulation and financial incentives remain essential to scale from niche polymers to large-scale bioplastic market applications with truly sustainable impact.
Infectious diseases are a major driver of morbidity and mortality globally. Treatment of malaria, tuberculosis and human immunodeficiency virus infection are particularly challenging, as indicated by ...the ongoing transmission and high mortality associated with these diseases. The formulation of new and existing drugs in nano-sized carriers promises to overcome several challenges associated with the treatment of these diseases, including low on-target bioavailability, sub-therapeutic drug accumulation in microbial sanctuaries and reservoirs, and low patient adherence due to drug-related toxicities and extended therapeutic regimens. Further, nanocarriers can be used for formulating vaccines, which represent a major weapon in our fight against infectious diseases. Here we review the current burden of infectious diseases with a focus on major drivers of morbidity and mortality. We then highlight how nanotechnology could aid in improving existing treatment modalities. We summarize our progress so far and outline potential future directions to maximize the impact of nanotechnology on the global population.
Devices that interact with living organisms are typically made of metals, silicon, ceramics, and plastics. Implantation of such devices for long-term monitoring or treatment generally requires ...invasive procedures. Hydrogels offer new opportunities for human-machine interactions due to their superior mechanical compliance and biocompatibility. Additionally, oral administration, coupled with gastric residency, serves as a non-invasive alternative to implantation. Achieving gastric residency with hydrogels requires the hydrogels to swell very rapidly and to withstand gastric mechanical forces over time. However, high swelling ratio, high swelling speed, and long-term robustness do not coexist in existing hydrogels. Here, we introduce a hydrogel device that can be ingested as a standard-sized pill, swell rapidly into a large soft sphere, and maintain robustness under repeated mechanical loads in the stomach for up to one month. Large animal tests support the exceptional performance of the ingestible hydrogel device for long-term gastric retention and physiological monitoring.
Biomacromolecules have transformed our capacity to effectively treat diseases; however, their rapid degradation and poor absorption in the gastrointestinal (GI) tract generally limit their ...administration to parenteral routes. An oral biologic delivery system must aid in both localization and permeation to achieve systemic drug uptake. Inspired by the leopard tortoise's ability to passively reorient, we developed an ingestible self-orienting millimeter-scale applicator (SOMA) that autonomously positions itself to engage with GI tissue. It then deploys milliposts fabricated from active pharmaceutical ingredients directly through the gastric mucosa while avoiding perforation. We conducted in vivo studies in rats and swine that support the applicator's safety and, using insulin as a model drug, demonstrated that the SOMA delivers active pharmaceutical ingredient plasma levels comparable to those achieved with subcutaneous millipost administration.
With >40 clinical trials underway, we are nearing the first FDA-approved live microbial therapeutic. Here, Giovanni Traverso, MIT and Harvard Medical School Assistant Professor, and colleagues Miguel ...Jimenez and Institute Professor Robert Langer from MIT discuss the significant challenges of administering live microorganisms to patients and the opportunities for drug delivery of these new complex therapeutics.
Biomolecular monitoring in the gastrointestinal tract could offer rapid, precise disease detection and management but is impeded by access to the remote and complex environment. Here, we present an ...ingestible micro-bio-electronic device (IMBED) for in situ biomolecular detection based on environmentally resilient biosensor bacteria and miniaturized luminescence readout electronics that wirelessly communicate with an external device. As a proof of concept, we engineer heme-sensitive probiotic biosensors and demonstrate accurate diagnosis of gastrointestinal bleeding in swine. Additionally, we integrate alternative biosensors to demonstrate modularity and extensibility of the detection platform. IMBEDs enable new opportunities for gastrointestinal biomarker discovery and could transform the management and diagnosis of gastrointestinal disease.
Oral delivery of therapeutics is the preferred route of administration due to ease of administration which is associated with greater patient medication adherence. One major barrier to oral delivery ...and intestinal absorption is rapid clearance of the drug and the drug delivery system from the gastrointestinal (GI) tract. To address this issue, researchers have investigated using GI mucus to help maximize the pharmacokinetics of the therapeutic; while mucus can act as a barrier to effective oral delivery, it can also be used as an anchoring mechanism to improve intestinal residence. Nano-drug delivery systems that use materials which can interact with the mucus layers in the GI tract can enable longer residence time, improving the efficacy of oral drug delivery. This review examines the properties and function of mucus in the GI tract, as well as diseases that alter mucus. Three broad classes of mucus-interacting systems are discussed: mucoadhesive, mucus-penetrating, and mucolytic drug delivery systems. For each class of system, the basis for mucus interaction is presented, and examples of materials that inform the development of these systems are discussed and reviewed. Finally, a list of FDA-approved mucoadhesive, mucus-penetrating, and mucolytic drug delivery systems is reviewed. In summary, this review highlights the progress made in developing mucus-interacting systems, both at a research-scale and commercial-scale level, and describes the theoretical basis for each type of system.
Designing therapeutics is a process with many challenges. Even if the first hurdle - designing a drug that modulates the action of a particular biological target
- is overcome, selective delivery to ...that target
presents a major barrier. Side-effects can, in many cases, result from the need to use higher doses without targeted delivery. However, the established use of macromolecules to encapsulate or conjugate drugs can provide improved delivery, and stands to enable better therapeutic outcomes. In this Review, we discuss how drug delivery approaches have evolved alongside our ability to prepare increasingly complex macromolecular architectures. We examine how this increased complexity has overcome the challenges of drug delivery and discuss its potential for fulfilling unmet needs in nanomedicine.
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