Versatile Synthesis and Fluorescent Labeling of ZIF-90 Nanoparticles for Biomedical Applications.

We describe a versatile method for the synthesis and fluorescent labeling of ZIF-90 nanoparticles (NPs). Gram-scale quantities of NPs can be produced under mild conditions, circumventing the need for high temperatures and extended reaction periods required by existing procedures. Monitoring the reaction in situ using UV-vis spectroscopy reveals that ZIF-90 NP nucleation in solution starts within seconds. In addition to reporting a method to reproducibly form sub-100 nm ZIF-90 particles, we show that particles of various sizes can be produced, ranging from 30 to 1000 nm, by altering amine chemistry or reaction temperature. The presence of linker aldehyde groups on the NP surface allows for postsynthetic labeling with amine-functionalized fluorescent dyes, providing utility for imaging within biological systems. In vitro cell studies show that ZIF-90 NPs have a high rate of cellular internalization, provide finite degradation periods of the order of several weeks, and are biocompatible with six different cell lines (>90% viable when incubated with NPs for up to 7 days). These features highlight the potential for use of ZIF-90 nanostructures in bioimaging and targeted drug delivery applications.

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

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.

Polymers for drug delivery systems.

Polymers have played an integral role in the advancement of drug delivery technology by providing controlled release of therapeutic agents in constant doses over long periods, cyclic dosage, and tunable release of both hydrophilic and hydrophobic drugs. From early beginnings using off-the-shelf materials, the field has grown tremendously, driven in part by the innovations of chemical engineers. Modern advances in drug delivery are now predicated upon the rational design of polymers tailored for specific cargo and engineered to exert distinct biological functions. In this review, we highlight the fundamental drug delivery systems and their mathematical foundations and discuss the physiological barriers to drug delivery. We review the origins and applications of stimuli-responsive polymer systems and polymer therapeutics such as polymer-protein and polymer-drug conjugates. The latest developments in polymers capable of molecular recognition or directing intracellular delivery are surveyed to illustrate areas of research advancing the frontiers of drug delivery.

Hydrogels in regenerative medicine.

Hydrogels, due to their unique biocompatibility, flexible methods of synthesis, range of constituents, and desirable physical characteristics, have been the material of choice for many applications in regenerative medicine. They can serve as scaffolds that provide structural integrity to tissue constructs, control drug and protein delivery to tissues and cultures, and serve as adhesives or barriers between tissue and material surfaces. In this work, the properties of hydrogels that are important for tissue engineering applications and the inherent material design constraints and challenges are discussed. Recent research involving several different hydrogels polymerized from a variety of synthetic and natural monomers using typical and novel synthetic methods are highlighted. Finally, special attention is given to the microfabrication techniques that are currently resulting in important advances in the field.