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Pluronic (PEO-PPO-PEO) block copolymers can form nano-sized micelles with a structure composed of a hydrophobic PPO core and hydrophilic PEO shell layer. Pluronics are U.S. Food and Drug Administration approved polymers, which are widely used for solubilization of drugs and their delivery, gene/therapeutic delivery, diagnostics, and tissue engineering applications due to their non-ionic properties, non-toxicity, micelle forming ability, excellent biocompatibility and biodegradability. Although Pluronics have been employed as drug carrier systems for several decades, numerous issues such as rapid dissolution, shorter residence time in biological media, fast clearance and weak mechanical strength have hindered their efficacy. Pluronics have been functionalized with pH-sensitive, biological-responsive moieties, antibodies, aptamers, folic acid, drugs, different nanoparticles, and photo/thermo-responsive hydrogels. These functionalization strategies enable Pluronics to act as stimuli responsive and targeted drug delivery vehicles. Moreover, Pluronics have emerged in nano-emulsion formulations and have been utilized to improve the properties of cubosomes, dendrimers and nano-sheets, including their biocompatibility and aqueous solubility. Functionalization of Pluronics results in the significant improvement of target specificity, loading capacity, biocompatibility of nanoparticles and stimuli responsive hydrogels for the promising delivery of a range of drugs. Therefore, this review presents an overview of all advancements (from the last 15 years) in functionalized Pluronics, providing a valuable tool for industry and academia in order to optimize their use in drug or therapeutic delivery, in addition to several other biomedical applications., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Microbubbles (MBs), which are used as ultrasonic contrast agents, have distinct acoustic signatures which enable them to significantly enhance visualisation of the vasculature. Research is progressing to develop MBs which act as drug/gene delivery vehicles for site-specific therapeutics. In order to manufacture effective theranostic vehicles, it is imperative to understand the mechanical and nanostructural properties of these agents; this will enrich the understanding of how the structural, biophysical and chemical properties of these bubbles impact their functionality. We produced microfluidic phospholipid-based MBs due to their favourable properties, such as biocompatibility and echogenicity, as well as the ability to modify the shell for targeting applications. We have drawn upon atomic force microscopy to conduct force spectroscopy and tapping-mode imaging investigations. We have, for the first time to our knowledge, been able to accurately quantify the thickness and lipid configuration of phospholipid-shelled MBs - showing a trilayer as opposed to the conventional monolayer structure. Furthermore, we have measured MB stiffness and employed different mechanical theories to quantify the Young's modulus. We show that the Reissner theory is inappropriate for mechanical characterisation of phospholipid MBs, however, the Hertz model does offer biologically relevant comparisons. Analysis using the Alexander-de Gennes polymer brush theory has allowed us to provide new information regarding how the thickness of the polyethylene glycol brushes, end-grafted to our phospholipid microbubbles, changes with diameter., (Copyright © 2019 Elsevier B.V. All rights reserved.)