Amphiphilic copolymers with bottlebrush architecture provide opportunities for the refinement of materials properties that may not be attainable from their linear analogues. In this study, we investigated the effect of polymer architecture on an interplay between molecular packing inside micelle cores, cargo loading, and core crosslinking. Four families of polylactide-b-poly(ethylene oxide) (PLA−PEO) bottlebrush block copolymers with different sidechain arrangements were synthesized by a combination of grafting-through and grafting-from methods. Copolymers with double-graft PLA side chains produced smaller and more uniform micelles than those with single-graft PLA branches. Photoactive coumarin groups, installed at PLA side chain ends, improved paclitaxel loading efficiencies of the copolymer micelles and allowed for the preparation of uniform, core-cross-linked PLA nanoparticles. The highest paclitaxel uptake (up to 30 wt % of the micelle core) was observed for micelles prepared from bottlebrush copolymers with branched PEO side chains, with paclitaxel uptake increasing with the size of PEO side chains. On the other hand, micelle photo-cross-linking efficiency was the highest (up to ∼90%) for copolymers with linear PEO side chains and decreased with increasing size of the hydrophilic headgroup. These trends were attributed to the decrease in molecular packing efficiency inside micelle cores for copolymers with larger and more rigid hydrophilic headgroups. For poorly packed micelles, paclitaxel loading improved core photo-cross-linking efficiencies, suggesting structural rearrangements inside micelles with cargo uptake. Preliminary results also showed that paclitaxel release from bottlebrush micelles was slowed down with increasing degree of core cross-linking.

Injectable hydrophobic drugs are typically dissolved in surfactants and non-aqueous solvents which can induce negative side-effects. Alternatives like ‘top-down' fine milling of excipient-free injectable drug suspensions are not yet clinically viable and ‘bottom-up' self-assembled delivery systems usually substitute one solubilizing excipient for another, bringing new issues to consider. Here, we show that Pluronic (Poloxamer) block copolymers are amenable to low-temperature processing to strip away all free and loosely bound surfactant, leaving behind concentrated, kinetically frozen drug micelles containing minimal solubilizing excipient. This approach was validated for phylloquinone, cyclosporine, testosterone undecanoate, cabazitaxel and seven other bioactive molecules, achieving sizes between 45 and 160 nm and drug to solubilizer molar ratios 2–3 orders of magnitude higher than current formulations. Hypertonic saline or co-loaded cargo was found to prevent aggregation in some cases. Use of surfactant-stripped micelles avoided potential risks associated with other injectable formulations. Mechanistic insights are elucidated and therapeutic dose responses are demonstrated.

A very sensitive and highly specific heterogeneous immunoassay system, based on surface-enhanced Raman scattering (SERS) and gold nanoparticles, was developed for the detection of bacteria and other pathogens. Two different types of gold nanoparticles (citrate-stabilized gold nanosphere and hexadecyltrimethylammonium bromide (CTAB)-stabilized gold nanorod particles) were examined and this immunoassay was applied for the detection of Escherichia coli. Raman labels were constructed by using these spherical and rod-shaped gold nanoparticles which were first coated with 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) and subsequently with a molecular recognizer. The working curve was obtained by plotting the intensity of the SERS signal of the symmetric NO(2) stretching of DTNB at 1,333 cm(-1) versus the concentration of the E. coli. The analytical performance of gold particles was evaluated via a sandwich immunoassay, and linear calibration graphs were obtained in the E. coli concentration range of 10(1)-10(5) cfu/mL with a 60-s accumulation time. The sensitivity of the Raman label fabricated with gold nanorods was more than three times higher than spherical gold nanoparticles. The selectivity of the developed sensor was examined with Enterobacter aerogenes and Enterobacter dissolvens, which did not produce any significant response. The usefulness of the developed immunoassay to detect E. coli in real water samples was also demonstrated.

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