Pilot Comparative Study of the Topical Action of a Novel, Crosslinked Resilient Hyaluronic Acid on Skin Hydration and Barrier Function in a Dynamic, Three-Dimensional Human Explant Model.

BACKGROUND: Hyaluronic acid (HA) is a popular ingredient in topical formulations for cosmetic improvement of the skin. Most formulations contain linear, non-crosslinked HA oligomers, low molecular weight (LMW) HA, and/or high molecular weight (HMW) HA. Crosslinking of HA enhances its clinical longevity and mechanical characteristics. The objective of this study was to characterize the topical effects of a new, crosslinked resilient HA (RHA) that is also available as a cohesive, tissue-integrating injectable filler, compared with non-crosslinked HMW HA and LMW HA. Living human skin explants that preserve the 3-dimensional structure of in vivo skin were used to maximize clinical relevance. METHODS: Standardized doses of each HA product were applied daily for 9 days to human skin explant surfaces. Untreated explants served as controls. Water content of the stratum corneum and entire epidermis was analyzed by Raman spectroscopy. Transepidermal water loss (TEWL) was measured to assess skin barrier function. Explant morphology and microrelief were evaluated by optical and scanning electron microscopy. RESULTS: Crosslinked RHA achieved a significant increase in epidermal water content (7.6%) over the control. Spectral cartography confirmed a higher epidermal water content with RHA than with HMW HA or LMW HA. TEWL was reduced by 27.8% with RHA, and by 15.6% with HMW HA, but increased by 55.5% with LMW HA. Cutaneous microrelief improved with RHA. Corneocyte cohesion improved with RHA and HMW HA. CONCLUSIONS: This comparative, multimodal study demonstrated greater benefits of topical crosslinked RHA over linear HMW HA or LMW HA in reducing TEWL, retaining and redistributing water within the epidermis, maintaining skin integrity, and improving skin barrier structure and function. RHA was a more efficacious humectant than LMW HA, and a more efficacious occlusive moisturizer than HMW HA. These integrative epidermal repair activities are of significant value for addressing primary deficits of aging skin, improving tolerance to retinoids and other topical agents, and optimizing procedural outcomes. A combination of topical and injectable HA provides an elegant model of synergistic, multi-level skin restoration.

RGD decoration of PEGylated polyester nanocapsules of perfluorooctyl bromide for tumor imaging: influence of pre or post-functionalization on capsule morphology.

PEGylated polyester nanocapsules of perfluorooctyl bromide (PFOB) were surface-decorated with a RGD (arginine-glycine-aspartic acid) peptide by either pre-functionalization or post-functionalization strategies using carbodiimide-assisted chemistry. Both strategies allowed successful linkage of RGD at the surface of nanocapsules with up to 600-950 peptide units per nanocapsule without modifying the encapsulation efficacy of PFOB used as the (19)F MRI imaging moiety. Cryo-Transmission Electron Microscopy images evidence that slight changes of the polymer used to form the capsule shell strongly influence nanocapsule morphology. While, the use of copolymer blends induces the formation of acorn morphologies, PLA-b-PEG-COOH leads to elongated and "tears of wine"-like nanoconstructs. In vivo evaluation in mice bearing CT26 tumors by (19)F MRI reveals no significant difference of accumulation between PEGylated and RGD-decorated nanocapsules obtained by the post-functionalization approach (highest RGD density/capsule).

Design, functionalization strategies and biomedical applications of targeted biodegradable/biocompatible polymer-based nanocarriers for drug delivery.

Design and functionalization strategies for multifunctional nanocarriers (e.g., nanoparticles, micelles, polymersomes) based on biodegradable/biocompatible polymers intended to be employed for active targeting and drug delivery are reviewed. This review will focus on the nature of the polymers involved in the preparation of targeted nanocarriers, the synthesis methods to achieve the desired macromolecular architecture, the selected coupling strategy, the choice of the homing molecules (vitamins, hormones, peptides, proteins, etc.), as well as the various strategies to display them at the surface of nanocarriers. The resulting morphologies and the main colloidal features will be given as well as an overview of the biological activities, with a special focus on the main in vivo achievements.

Drug delivery and imaging with polydiacetylene micelles.

This concept article summarizes our recent findings regarding photopolymerized micelles obtained from the self-assembly of diacetylene-containing amphiphiles. Their synthesis and characterization are presented as well as some biomedical applications, such as tumor imaging and drug delivery. Finally, ongoing studies and future challenges are briefly discussed.

Tumor-targeted polydiacetylene micelles for in vivo imaging and drug delivery.

In vivo tumor targeting and drug delivery properties of small polymerized polydiacetylene (PDA) micelles (∼10 nm) is investigated in a murine MDA-MB-231 xenograft model of breast cancer. Three micelles with different surface coatings are synthesized and tested for their ability to passively target tumor through the enhanced permeability and retention effect. After injection (24 h), fluorescence diffuse optical tomographic imaging indicates a tumor uptake of nearly 3% of the injected dose for the micelles with a 2 kDa poly(ethylene glycol) (PEG)-coating (PDA-PEG2000). The uptake of PDA micelles in tumors is confirmed by co-localization with [(18) F]-fluorodeoxyglucose (FDG) positron emission tomography. Although FDG has a higher diffusion rate in tumors, 40 ± 19% of the retained micelles is co-registered with the tumor volume visualized by FDG. Finally, PDA-PEG2000 micelles are loaded with the hydrophobic anticancer drug paclitaxel and used in vivo to inhibit tumor growth. These findings demonstrate the potential of PDA-PEG2000 micelles for both in vivo tumor imaging and drug delivery applications.

Colloidal properties of biodegradable nanoparticles influence interaction with amyloid-ß peptide.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the extracellular deposition of amyloid-ß peptides (Aß). During the past few years, promising approaches based on nanotechnologies have emerged to alter Aß aggregation and its related toxicity. This study aims to investigate the influence of the nanoparticle colloidal properties over the interaction with Aß peptide 1-42 (Aß(1-42)). Using capillary electrophoresis with laser-induced fluorescence detection, it was shown that biodegradable poly(ethylene glycol)-block-polylactide (PEG-b-PLA) nanoparticles were able to interact with Aß(1-42) peptide leading to its uptake in rather short time periods. In addition, we highlighted the crucial role of the nanocarrier colloidal properties on the uptake kinetics. Whereas nanoparticles stabilized by sodium cholate (lower size and higher negative surface charge) gave optimum uptake kinetics, nanoparticles stabilized with others surfactants presented lower interactions. In contrast, PEG density seemed to have no influence on the interaction when sodium cholate was used for the preparation. This study intends to give new insights into Aß(1-42) peptide interaction with nanoparticulate systems by helping to determine suitable nanoparticle characteristics regarding forthcoming therapeutic strategies against AD.

In vivo validation of free-space fluorescence tomography using nuclear imaging.

The performance of small animal photonic imaging has been considerably improved since the development of fluorescence diffuse optical tomography (fDOT), which can reconstruct fluorescent probe distribution inside tissue. However, the quantification capabilities of this new technology are still a topic of debate, especially in comparison to classical nuclear imaging techniques. Here, we present a method to in vivo calibrate the quantity and localization of a probe provided by free-space fDOT (where no plate is compressing the mouse) with positron emission tomography (PET) and x-ray computed tomography, respectively. This methodology allowed us to demonstrate a strong linear correlation (R(2)=0.95) between fDOT and PET for probe concentrations ranging from 3 nM to 1 µM in a deep-seated organ.

Carbon nanotube-acridine nanohybrids: spectroscopic characterization of photoinduced electron transfer.

Single-walled carbon nanotubes (NT) were covalently functionalized with either 9-phenyl acridine (PhA) or 10-methyl-9-phenyl acridinium (PhMeA(+)). Absorption and fluorescence properties of acridine derivatives tethered to the nanotubes were studied in homogeneous dispersions. Exciplex emission was observed for NT functionalized with 9-phenylacridine. This phenomenon was attributed to an "intramolecular" interaction between excited phenyl acridine and carbon nanotubes. Interestingly, reverse photoinduced electron transfer from the nanotube to 10-methyl-9-phenylacridinium was detected for the NT-PhMeA(+) nanohybrid. This electron transfer led to a strong quenching of the acridinium fluorescence and to the formation of a metastable acridine radical. Evidence for the formation of this radical was obtained by ESR studies.

Supramolecular self-assembly of amphiphiles on carbon nanotubes: a versatile strategy for the construction of CNT/metal nanohybrids, application to electrocatalysis.

Homogeneous coating of carbon nanotubes with metallic nanoparticles was achieved using supramolecular auto-organization of amphiphilic molecules as template. The resulting Pd nanoparticles/carbon nanotube nanohybrids were then evaluated in electrocatalysis experiments, showing superior activity in ethanol oxidation compared to analogous systems.