Mechanically matching the rheological properties of brain tissue for drug-delivery in human glioblastoma models.

Peptide functionalized hyaluronic acid (HACF) cross-linked by cucurbit[8]uril (CB[8]), a new class of drug-delivery reservoirs, is used to enable improved drug bioavailability for glioblastoma tumors in patient-derived xenograft (PDX) models. The mechanical and viscoelastic properties of native human and mouse tissues are measured over 8 h via oscillatory rheology under physiological conditions. Treatment with drug-loaded hydrogels allowed for a significant survival impact of 45 % (55.5-80.5 days). A relationship between the type of PDX tumor formed-a consequence of the heterogeneic nature of GB tumors-and changes in the initial survival is observed owing to greater local pressure from stiffer tumors. These biocompatible and tailorable materials warrant use as drug delivery reservoirs in PDX resection models, where the mechanical properties can be readily adjusted to match the stiffness of local tissue and thus have potential to improve the survival of GB patients.

Design Principles for Aqueous Interactive Materials: Lessons from Small Molecules and Stimuli-Responsive Systems.

Interactive materials are at the forefront of current materials research with few examples in the literature. Researchers are inspired by nature to develop materials that can modulate and adapt their behavior in accordance with their surroundings. Stimuli-responsive systems have been developed over the past decades which, although often described as "smart," lack the ability to act autonomously. Nevertheless, these systems attract attention on account of the resultant materials' ability to change their properties in a predicable manner. These materials find application in a plethora of areas including drug delivery, artificial muscles, etc. Stimuli-responsive materials are serving as the precursors for next-generation interactive materials. Interest in these systems has resulted in a library of well-developed chemical motifs; however, there is a fundamental gap between stimuli-responsive and interactive materials. In this perspective, current state-of-the-art stimuli-responsive materials are outlined with a specific emphasis on aqueous macroscopic interactive materials. Compartmentalization, critical for achieving interactivity, relies on hydrophobic, hydrophilic, supramolecular, and ionic interactions, which are commonly present in aqueous systems and enable complex self-assembly processes. Relevant examples of aqueous interactive materials that do exist are given, and design principles to realize the next generation of materials with embedded autonomous function are suggested.

Coordination cages as permanently porous ionic liquids.

Porous materials are widely used in industry for applications that include chemical separations and gas scrubbing. These materials are typically porous solids, although the liquid state can be easier to manipulate in industrial settings. The idea of combining the size and shape selectivity of porous domains with the fluidity of liquids is a promising one and porous liquids composed of functionalized organic cages have recently attracted attention. Here we describe an ionic-liquid, porous, tetrahedral coordination cage. Complementing the gas binding observed in other porous liquids, this material also encapsulates non-gaseous guests-shape and size selectivity was observed for a series of isomeric alcohols. Three gaseous chlorofluorocarbon guests, trichlorofluoromethane, dichlorodifluoromethane and chlorotrifluoromethane, were also shown to be taken up by the liquid coordination cage with an affinity that increased with their size. We hope that these findings will lead to the synthesis of other porous liquids whose guest-uptake properties may be tailored to fulfil specific functions.

Designing Next-Generation Local Drug Delivery Vehicles for Glioblastoma Adjuvant Chemotherapy: Lessons from the Clinic.

To date, the clinical outcomes and survival rates for patients with glioblastoma (GB) remain poor. A promising approach to disease-modification involves local delivery of adjuvant chemotherapy into the resection cavity, thus circumventing the restrictions imposed by the blood-brain barrier. The clinical performance of the only FDA-approved local therapy for GB [carmustine (BCNU)-loaded polyanhydride wafers], however, has been disappointing. There is an unmet medical need in the local treatment of GB for drug delivery vehicles that provide sustained local release of small molecules and combination drugs over several months. Herein, key quantitative lessons from the use of local and systemic adjuvant chemotherapy for GB in the clinic are outlined, and it is discussed how these can inform the development of next-generation therapies. Several recent approaches are highlighted, and it is proposed that long-lasting soft materials can capture the value of stiff BCNU-loaded wafers while addressing a number of unmet medical needs. Finally, it is suggested that improved communication between materials scientists, biomedical scientists, and clinicians may facilitate translation of these materials into the clinic and ultimately lead to improved clinical outcomes.

An adherent tissue-inspired hydrogel delivery vehicle utilised in primary human glioma models.

A physical hydrogel cross-linked via the host-guest interactions of cucurbit[8]uril and utilised as an implantable drug-delivery vehicle for the brain is described herein. Constructed from hyaluronic acid, this hydrogel is biocompatible and has a high water content of 98%. The mechanical properties have been characterised by rheology and compared with the modulus of human brain tissue demonstrating the production of a soft material that can be moulded into the cavity it is implanted into following surgical resection. Furthermore, effective delivery of therapeutic compounds and antibodies to primary human glioblastoma cell lines is showcased by a variety of in vitro and ex vivo viability and immunocytochemistry based assays.