Poly(glycidol) Coating on Ultrahigh Molecular Weight Polyethylene for Reduced Biofilm Growth.

Semibranched poly(glycidol) (PG-OH) and poly(glycidol allylglycidyl ether) (PG-Allyl) coatings were formed on ultrahigh molecular weight polyethylene (UMWPE) in a unique two-step process which included radiation of UHMWPE followed by grafting of PG-OH or PG-Allyl to the surface via free radical cross-linking. Resulting surfaces were extensively characterized by FTIR-ATR, XPS, fluorescent microscopy, and contact goniometry. The performance was evaluated using the most prominent biofilm-forming bacteria Staphylococcus aureus for 24 and 48 h. The PG-Allyl coating demonstrated a 3 log reduction in biofilm growth compared to noncoated control, demonstrating a promising potential to inhibit adherence and colonization of biofilm-forming bacteria that often develop into persistent infections.

One-pot polyglycidol nanogels via liposome master templates for dual drug delivery.

Polyglycidol-based nanohydrogels (nHGs) have been prepared by optimizing the use of liposome master templates resulting in a high-yielding and more practical one-pot process to provide materials capable of carrying drugs of adverse chemical nature. The nanogels prepared with the one-pot method showed favorable kinetics for the release of either Nile Red (NR) or lysozyme (LYS), loaded with gel precursors such as semi-branched poly(glycidol allylglycidyl ether), PEG dithiol (1KDa), a free radical initiator and liposomal lipids at the liposome formation step. This process is superior to a comparable step-wise traditional approach and circumvents loading of the gel precursors with the hydrophilic drug into preformed liposome templates. A thiol-ene crosslinking reaction accomplishes the formation of the nanonetwork resulting in nHGs prepared in the traditional step-wise (nHG-SW) approach and the one-pot (nHG-OP) process. Both nanogel networks were characterized in terms of particle size and zeta (ζ) potential with average values of 148nm±39nm and -25.9mV±9.2 for the nHG-SW and 132nm±32 and -23.1mV±9.7 for the nHG-OPs. Loading efficiency for both of the nanogels with NR was determined by spectrophotometry to be 28% (nHP-SW) and 31% (nHP-OP). The LYS loading was based on the target loading of 10µg/mg for both nanogels found to be 84% and 86% for the nHG-SW and nHP-OP, respectively. As proof of concept for combination drug delivery, the in vitro release of both drug mimics, NR and LYS, were monitored under physiologically relevant conditions by an optimized dialysis method. The implementation of the multi-functional and semi-branched polyglycidol is recognized as the main contributor for the observed highly controlled release of proteins that are otherwise rapidly released from common PEG-based nanogel networks. Furthermore, the one-pot process led to be the most favorable drug delivery system based on the release kinetics pointing to a denser polymer network.

Dual drug delivery of tamoxifen and quercetin: Regulated metabolism for anticancer treatment with nanosponges.

We report the synthesis and encapsulation of polyester nanosponge particles (NPs) co-loaded with tamoxifen (TAM) and quercetin (QT) to investigate the loading, release and in vitro metabolism of a dual drug formulation. The NPs are made in two variations, 4% and 8% crosslinking densities, to evaluate the effects on metabolism and release kinetics. The NP-4% formulation with a particle size of 89.3 ± 14.8 nm was found to have loading percentages of 6.91 ± 0.13% TAM and 7.72 ± 0.15% QT after targeting 10% (w/w) each. The NP-8% formulation with a particle size of 91.5 ± 9.8 nm was found to have loading percentages of 7.26 ± 0.10% TAM and 7.80 ± 0.12% QT. The stability of the formulation was established in simulated gastrointestinal fluids, and the metabolism of TAM was shown to be reduced 2-fold and 3-fold for NP-4%s and NP-8%s, respectively, while QT metabolism was reduced 3 and 4-fold. The implications for improved bioavailability of the NP formulations were supported by cytotoxicity results that showed a similar efficacy to free dual drug formulations and even enhanced anti-cancer effects in the recovery condition. This work demonstrates the suitability of the nanosponges not only as a dual release drug delivery system but also enabling a regulated metabolism through the capacity of a nanonetwork. The variation in crosslinking enables a dual release with tailored release kinetics and suggests improved bioavailability aided by a reduced metabolism.