Showing papers by "Nicholas A. Peppas published in 2014"

25th Anniversary Article: Rational Design and Applications of Hydrogels in Regenerative Medicine

Abstract: Hydrogels are hydrophilic polymer-based materials with high water content and physical characteristics that resemble the native extracellular matrix. Because of their remarkable properties, hydrogel systems are used for a wide range of biomedical applications, such as three-dimensional (3D) matrices for tissue engineering, drug-delivery vehicles, composite biomaterials, and as injectable fillers in minimally invasive surgeries. In addition, the rational design of hydrogels with controlled physical and biological properties can be used to modulate cellular functionality and tissue morphogenesis. Here, the development of advanced hydrogels with tunable physiochemical properties is highlighted, with particular emphasis on elastomeric, light-sensitive, composite, and shape-memory hydrogels. Emerging technologies developed over the past decade to control hydrogel architecture are also discussed and a number of potential applications and challenges in the utilization of hydrogels in regenerative medicine are reviewed. It is anticipated that the continued development of sophisticated hydrogels will result in clinical applications that will improve patient care and quality of life.

Nanocomposite hydrogels for biomedical applications.

Abstract: Hydrogels mimic native tissue microenvironment due to their porous and hydrated molecular structure. An emerging approach to reinforce polymeric hydrogels and to include multiple functionalities focuses on incorporating nanoparticles within the hydrogel network. A wide range of nanoparticles, such as carbon-based, polymeric, ceramic, and metallic nanomaterials can be integrated within the hydrogel networks to obtain nanocomposites with superior properties and tailored functionality. Nanocomposite hydrogels can be engineered to possess superior physical, chemical, electrical, and biological properties. This review focuses on the most recent developments in the field of nanocomposite hydrogels with emphasis on biomedical and pharmaceutical applications. In particular, we discuss synthesis and fabrication of nanocomposite hydrogels, examine their current limitations and conclude with future directions in designing more advanced nanocomposite hydrogels for biomedical and biotechnological applications.

Hydrogels and Scaffolds for Immunomodulation

Abstract: For over two decades, immunologists and biomaterials scientists have co-existed in parallel world with the rationale of understanding the molecular profile of immune responses to vaccination, implantation, and treating incurable diseases. Much of the field of biomaterial-based immunotherapy has relied on evaluating model antigens such as chicken egg ovalbumin in mouse models but their relevance to humans has been point of much discussion. Nevertheless, such model antigens have provided important insights into the mechanisms of immune regulation and served as a proof-of-concept for plethora of biomaterial-based vaccines. After years of extensive development of numerous biomaterials for immunomodulation, it is only recently that an experimental scaffold vaccine implanted beneath the skin has begun to use the human model to study the immune responses to cancer vaccination by co-delivering patient-derived tumor lysates and immunomodulatory proteins. If successful, this scaffold vaccine will change the way we approached untreatable cancers, but more importantly, will allow a faster and more rational translation of therapeutic regimes to other cancers, chronic infections, and autoimmune diseases. Most materials reviews have focused on immunomodulatory adjuvants and micro-nano-particles. Here we provide an insight into emerging hydrogel and scaffold based immunomodulatory approaches that continue to demonstrate efficacy against immune associated diseases.

Therapeutic applications of hydrogels in oral drug delivery.

Abstract: Introduction: Oral delivery of therapeutics, particularly protein-based pharmaceutics, is of great interest for safe and controlled drug delivery for patients. Hydrogels offer excellent potential as oral therapeutic systems due to inherent biocompatibility, diversity of both natural and synthetic material options and tunable properties. In particular, stimuli-responsive hydrogels exploit physiological changes along the intestinal tract to achieve site-specific, controlled release of protein, peptide and chemotherapeutic molecules for both local and systemic treatment applications. Areas covered: This review provides a wide perspective on the therapeutic use of hydrogels in oral delivery systems. General features and advantages of hydrogels are addressed, with more considerable focus on stimuli-responsive systems that respond to pH or enzymatic changes in the gastrointestinal environment to achieve controlled drug release. Specific examples of therapeutics are given. Last, in vitro and in vivo methods to e...

Multi-responsive hydrogels for drug delivery and tissue engineering applications

Abstract: Multi-responsive hydrogels, or ‘intelligent’ hydrogels that respond to more than one environmental stimulus, have demonstrated great utility as a regenerative biomaterial in recent years. They are structured biocompatible materials that provide specific and distinct responses to varied physiological or externally applied stimuli. As evidenced by a burgeoning number of investigators, multi-responsive hydrogels are endowed with tunable, controllable and even biomimetic behavior well-suited for drug delivery and tissue engineering or regenerative growth applications. This article encompasses recent developments and challenges regarding supramolecular, layer-by-layer assembled and covalently cross-linked multi-responsive hydrogel networks and their application to drug delivery and tissue engineering.

Polycationic Nanoparticles for siRNA Delivery: Comparing ARGET ATRP and UV-Initiated Formulations

Abstract: In this work, we develop and evaluate polycationic nanoparticles for the delivery of small interfering RNA (siRNA). Delivery remains a major challenge for translating siRNA to the clinic, and overcoming the delivery challenge requires effective siRNA delivery vehicles that meet the demands of the specific delivery strategy. Cross-linked polycationic nanoparticle formulations were synthesized using ARGET ATRP or UV-initiated polymerization. The one-step, one-pot, surfactant-stabilized monomer-in-water synthesis technique may provide a simpler and faster alternative to complicated, multistep techniques and an alternative to methods that rely on toxic organic solvents. The polymer nanoparticles were synthesized using the cationic monomer 2-(diethylamino)ethyl methacrylate, the hydrophobic monomer tert-butyl methacrylate to tune pH responsiveness, the hydrophilic monomer poly(ethylene glycol) methyl ether methacrylate to improve biocompatibility, and cross-linking agent tetraethylene glycol dimethacrylate to enhance colloidal stability. Four formulations were evaluated for their suitability as siRNA delivery vehicles in vitro with the human embryonic kidney cell line HEK293T or the murine macrophage cell line RAW264.7. The polycationic nanoparticles demonstrated efficient and rapid loading of the anionic siRNA following complexation. Confocal microscopy as well as flow cytometry analysis of cells treated with polycationic nanoparticles loaded with fluorescently labeled siRNA demonstrated that the polycationic nanoparticles promoted cellular uptake of fluorescently labeled siRNA. Knockdown experiments using polycationic nanoparticles to deliver siRNA demonstrated evidence of knockdown, thus demonstrating potential as an alternative route to creating polycationic nanoparticles.

Intelligent recognitive systems in nanomedicine

Abstract: There is a bright future in the development and utilization of nanoscale systems based on intelligent materials that can respond to external input providing a beneficial function. Specific functional groups can be incorporated into polymers to make them responsive to environmental stimuli such as pH, temperature, or varying concentrations of biomolecules. The fusion of such "intelligent" biomaterials with nanotechnology has led to the development of powerful therapeutic and diagnostic platforms. For example, targeted release of proteins and chemotherapeutic drugs has been achieved using pH-responsive nanocarriers while biosensors with ultra-trace detection limits are being made using nanoscale, molecularly imprinted polymers. The efficacy of therapeutics and the sensitivity of diagnostic platforms will continue to progress as unique combinations of responsive polymers and nanomaterials emerge.

Multiresponsive polyanionic microgels with inverse pH responsive behavior by encapsulation of polycationic nanogels

Abstract: Intelligent, stimuli-responsive hydrogels have great utility in various fields spanning biomedical technology, separations, and catalysis. Their overall response to surrounding fluids may be further tailored to a specific application by incorporation of one or more intelligent responses within one material, known as multiresponsive hydrogels. This is a report on the facile synthesis and characterization of poly(methacrylic acid-co-N-vinylpyrrolidone) microgels encapsulating polycationic nanogels (70–100 nm) to incorporate inverse pH responsive behavior within a single hydrogel. Potentiometric titration and pH swelling studies reveal a swelling response dependent on both pH and crosslinking agent. Additionally, a protein and a small molecule are loaded and released to evaluate the pH-dependent binding affinity. Such a material could exhibit unique protein-binding capacity and pH-responsive behavior for use in separation or drug delivery applications. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40098.

Polymeric Nanocarriers for siRNA Delivery to Murine Macrophages

Abstract: This work investigates the interactions of a polycationic nanocarrier with siRNA and with cells in order to better understand the capabilities and limitations of the carrier. The polycationic nanocarriers are cross-linked copolymer nanoparticles synthesized in a single-step reaction using ARGET ATRP (activators regenerated by electron transfer atom transfer radical polymerization). The polycationic nanocarriers efficiently bind siRNA for polymer/siRNA mass ratios less than 1. A method to prepare fluorescently labeled polycationic nanocarriers is presented. The fluorescently labeled polycationic nanocarriers are used to investigate cellular internalization with RAW264.7 murine macrophage cells. Flow cytometry demonstrates that the uptake increased with nanoparticle concentration and incubation time. Confocal microscopy confirmed internalization of fluorescently labeled nanoparticles. The investigation of siRNA-induced knockdown demonstrates that higher concentrations of nanoparticles and siRNA are associated with increased knockdown. For the conditions tested in the knockdown experiments, the ARGET ATRP polycationic nanocarriers outperformed a commercially available Lipofectamine control.

Method of preparation of biodegradable nanoparticles with recognition characteristics

Abstract: The present disclosure relates to a novel type of recognitive biodegradable nanoparticles and their preparations. In particular, the present disclosure relates to combinations of MIPs and biodegradable nanoparticles. One aspect of the present disclosure is directed to a composition comprising: an outer shell having at least one binding cavity specific for a target molecule; and a biodegradable inner core substantially free of the binding cavity.