Various local drug delivery devices and coatings are being developed as slow, sustained release mechanism for drugs, yet the polymers are typically not evaluated after commercial sterilization techniques. We examine the effect that commercial sterilization techniques have on the physical, mechanical, and drug delivery properties of polyurethane polymers. Specifically we tested cyclodextrin-hexamethyl diisocyanate crosslinked polymers before and after autoclave, ethylene oxide, and gamma radiation sterilization processes. We found that there is no significant change in the properties of polymers sterilized by ethylene oxide and gamma radiation compared to non-sterilized polymers. Polymers sterilized by autoclave showed increased tensile strength (p<0.0001) compared to non-sterilized polymers . In the release of drugs, which were loaded after the autoclave sterilization process, we observed a prolonged release (p<0.05) and a prolonged therapeutic effect (p<0.05) but less drug loading (p<0.0001) compared to non-sterilized polymers. The change in the release profile and tensile strength in polymers sterilized by autoclave was interpreted as being caused by additional crosslinking from residual, unreacted, or partially-reacted crosslinker contained within the polymer. Autoclaving therefore represents additional thermo-processing to modify rate and dose from polyurethanes and other materials.

The development of new therapies for surgical adhesions has proven to be difficult as there is no consistently effective way to assess treatment efficacy in clinical trials without performing a second surgery, which can result in additional adhesions. We have developed lipid microbubble formulations that use a short peptide sequence, CREKA, to target fibrin, the molecule that forms nascent adhesions. These targeted polymerized shell microbubbles (PSMs) are designed to allow ultrasound imaging of early adhesions for diagnostic purposes and for evaluating the success of potential treatments in clinical trials while acting as a possible treatment. In this study, we show that CREKA-targeted microbubbles preferentially bind fibrin over fibrinogen and are stable for long periods of time (~48 h), that these bound microbubbles can be visualized by ultrasound, and that neither these lipid-based bubbles nor their diagnostic-ultrasound-induced vibrations damage mesothelial cells in vitro. Moreover, these bubbles show the potential to identify adhesionlike fibrin formations and may hold promise in blocking or breaking up fibrin formations in vivo.

A diverse range of clinical infections are on the increase, resulting in part from disruption of the natural microbiome, or even mycobiome, as a result of many different medical interventions. Amphotericin B (AmB) is a leading drug for the treatment of clinical fungal infections. However, AmB is extremely cytotoxic to mammalian cells, making use of the drug problematic. In this work, a drug delivery system made of polymerized cyclodextrin (pCD) allows for the localized administration of AmB, reducing the toxicity to host cells while retaining antifungal activity. A slow, sustained delivery rate of AmB was achieved through exploiting molecular interactions between the CD pockets and the drug. Surface plasmon resonance (SPR) and Fourier transform infrared spectroscopy (FTIR) were used to characterize the interaction between AmB and cyclodextrins (CDs). Through these methods, it was found that amphotericin binds strongly ([Formula: see text]M−1) to β-cyclodextrin. Release studies showed slow, sustained release of AmB from pCD disks. Antifungal activity was tested against Saccharomyces cerevisiae in assays for zone of inhibition, contact killing, and solution killing. In all assays, AmB-loaded pCD disks were found to exhibit significant antifungal activity. These results indicate that AmB-loaded pCD disks are capable of both the prevention of fungal growth and the elimination of established colonies. Additionally, results suggest that AmB exhibits antifungal activity whether associated with or released from pCD. The usage of pCD as a delivery vehicle also significantly reduces the toxic side effects of AmB, as seen in mammalian cell culture studies. These results show that in addition to reducing side-effects from systemic dosing, local delivery of AmB from pCD disks has the potential to improve its usage both in antifungal efficacy and reduced mammalian cell toxicity. Impact statement Amphotericin B (AmB) is an effective and commonly used antifungal agent. However, nephrotoxicity and poor solubility limits its usage. The proposed polymerized cyclodextrin (pCD) system therefore is an attractive method for AmB delivery, as it retains the antifungal activity of AmB while decreasing toxicity, and confining drug release to the local environment. This system could potentially be used for both prevention and treatment of established fungal infections, as AmB is toxic to fungus whether associated or released from pCD.

Rationale: High mortality in pancreatic cancer (PDAC) and triple negative breast cancer (TNBC) highlight the need to capitalize on nanoscale-design advantages for multifunctional diagnostics and therapies. DNA/RNA-therapies can provide potential breakthroughs, however, to date, there is no FDA-approved systemic delivery system to solid tumors. Methods: Here, we report a Janus-nanoparticle (jNP)-system with modular targeting, payload-delivery, and targeted-imaging capabilities. Our jNP-system consists of 10 nm ultrasmall superparamagnetic iron oxide nanoparticles (USPION) with opposing antibody-targeting and DNA/RNA payload-protecting faces, directionally self-assembled with commercially available zwitterionic microbubbles (MBs) and DNA/RNA payloads. Results: Sonoporation of targeted jNP-payload-MBs delivers functional reporter-DNA imparting tumorfluorescence, and micro-RNA126 reducing non-druggable KRAS in PDAC-Panc1 and TNBC-MB231 xenografted tumors. The targeting jNP-system enhances ultrasound-imaging of intra-tumoral microvasculature using less MBs/body weight (BW). The jNP-design enhances USPION's T2*-magnetic resonance (MR) and MR-imaging of PDAC-peritoneal metastases using less Fe/BW. Conclusion: Altogether, data advance the asymmetric jNP-design as a potential theranostic Janus-USPION Modular Platform -a JUMP forward.