Showing papers by "Nicholas A. Peppas published in 2015"

Stimulus-responsive hydrogels: Theory, modern advances, and applications

Abstract: Over the past century, hydrogels have emerged as effective materials for an immense variety of applications. The unique network structure of hydrogels enables very high levels of hydrophilicity and biocompatibility, while at the same time exhibiting the soft physical properties associated with living tissue, making them ideal biomaterials. Stimulus-responsive hydrogels have been especially impactful, allowing for unprecedented levels of control over material properties in response to external cues. This enhanced control has enabled groundbreaking advances in healthcare, allowing for more effective treatment of a vast array of diseases and improved approaches for tissue engineering and wound healing. In this extensive review, we identify and discuss the multitude of response modalities that have been developed, including temperature, pH, chemical, light, electro, and shear-sensitive hydrogels. We discuss the theoretical analysis of hydrogel properties and the mechanisms used to create these responses, highlighting both the pioneering and most recent work in all of these fields. Finally, we review the many current and proposed applications of these hydrogels in medicine and industry.

Intelligent Nanoparticles for Advanced Drug Delivery in Cancer Treatment

Abstract: Treatment of cancer using nanoparticle-based approaches relies on the rational design of carriers with respect to size, charge, and surface properties. Polymer-based nanomaterials, inorganic materials such as gold, iron oxide, and silica as well as carbon based materials such as carbon nanotubes and graphene are being explored extensively for cancer therapy. The challenges associated with the delivery of these nanoparticles depend greatly on the type of cancer and stage of development. This review highlights design considerations to develop nanoparticle-based approaches for overcoming physiological hurdles in cancer treatment, as well as emerging research in engineering advanced delivery systems for the treatment of primary, metastatic, and multidrug resistant cancers. A growing understanding of cancer biology will continue to foster development of intelligent nanoparticle-based therapeutics that take into account diverse physiological contexts of changing disease states to improve treatment outcomes.

Dynamic swelling behavior of interpenetrating polymer networks in response to temperature and pH

Abstract: Temperature responsive hydrogels based on ionic polymers exhibit swelling transitions in aqueous solutions as a function of shifting pH and ionic strength, in addition to temperature. Applying these hydrogels to useful applications, particularly for biomedical purposes such as drug delivery and regenerative medicine, is critically dependent on understanding the hydrogel solution responses as a function of all three parameters together. In this work, interpenetrating polymer network (IPN) hydrogels of polyacrylamide and poly(acrylic acid) were formulated over a broad range of synthesis variables using a fractional factorial design, and were examined for equilibrium temperature responsive swelling in a variety of solution conditions. Due to the acidic nature of these IPN hydrogels, usable upper critical solution temperature (UCST) responses for this system occur in mildly acidic environments. Responses were characterized in terms of maximum equilibrium swelling and temperature-triggered swelling using turbidity and gravimetric measurements. Additionally, synthesis parameters critical to achieving optimal overall swelling, temperature-triggered swelling, and sigmoidal temperature transitions for this IPN system were analyzed based on the fractional factorial design used to formulate these hydrogels.

Complexation Hydrogels as Oral Delivery Vehicles of Therapeutic Antibodies: An in Vitro and ex Vivo Evaluation of Antibody Stability and Bioactivity.

Abstract: Oral administration of monoclonal antibodies (mAbs) may enable the localized treatment of infections or other conditions in the gastrointestinal tract (GI) as well as systemic diseases. As with the development of oral protein biotherapeutics, one of the most challenging tasks in antibody therapies is the loss of biological activity due to physical and chemical instabilities. New families of complexation hydrogels with pH-responsive properties have demonstrated to be excellent transmucosal delivery vehicles. This contribution focuses on the design and evaluation of hydrogel carriers that will minimize the degradation and maximize the in vivo activity of anti-TNF-α, a mAb used for the treatment of inflammatory bowel disease (IBD) in the GI tract and systemically for the treatment of rheumatoid arthritis. P(MAA-g-EG) and P(MAA-co-NVP) hydrogels systems were optimized to achieve adequate swelling behavior, which translated into improved protein loading and release at neutral pH simulating the small intestine conditions. Additionally, these hydrogel systems preserve antibody bioactivity upon release resulting in the systemic circulation of an antibody capable of effectively performing its biological function. The compatibility if these hydrogels for mAb bioactivity preservation and release makes them candidates for use as oral delivery systems for therapeutic antibodies.

Intelligent, responsive and theranostic hydrogel systems for controlled delivery of therapeutics

Abstract: Hydrogels are hydrophilic polymers that have been crosslinked to form a three-dimensional polymer matrix as shown. Under the correct environmental conditions, these materials can imbibe significant amounts of water, often over two orders of magnitude more water than polymer by weight. Due to the large water content, hydrogels are currently the synthetic materials that most resemble living tissue. These properties help make hydrogels ideal for use in tissue engineering, drug delivery, surface coatings, contact lenses, wound dressings, and even polluted water treatment. Swollen crosslinked networks and hydrogels have been influential in the improvement of polymeric systems for controlled release of a wide variety of therapeutic agents. These materials are attractive as carriers for transmucosal and intracellular drug delivery because of their inherent biocompatibility, tunable physicochemical properties, basic synthesis, and ability to be physiologically responsive.

Delivery of small interfering rna and micro rna through nanogels containing hydrophobic pseudo-peptides

Abstract: Nanoscale, pH-responsive polycationic networks useful for the delivery of anionic biologic therapeutics and associated methods.

Polymers for delivery of factor viii and/or factor ix

Abstract: In some aspects, a composition comprising a pH-sensitive crosslinked copolymer of methacrylic acid and poly(ethylene glycol) monomethyl ether methacrylate and a therapeutic protein is provided. In some embodiments, the therapeutic protein is a high molecular weight protein such as factor VIII or factor IX. In some embodiments, the composition is orally administered to a patient to treat a disease or disorder such as, e.g., hemophilia.

Protein Imprinting by Means of Alginate-Based Polymers

Abstract: Methods of preparing molecularly imprinted polymers are provided. In one embodiment, a method comprises providing a solution comprising a template molecule; and forming a product comprising calcium alginate in the presence of the template molecule so that the template molecule is imprinted in the product.