One-pot Formulation of Cationic Oligochitosan Coated Nanoparticles via Photo- Polymerization Induced Self-Assembly.

During last few decades, oligochitosan (OCS)-coated nanoparticles have received great interest for nanomedicine, food and environment applications. However, their current formulation techniques are time-consuming with multi-synthesis/purification steps and sometimes require the use of organic solvents, crosslinkers and surfactants. Herein, we report a facile and rapid one-pot synthesis of OCS-based nanoparticles using photo-initiated reversible addition fragmentation chain transfer polymerization-induced self-assembly (Photo-RAFT PISA) under UV-irradiation at room temperature. To achieve this, OCS was first functionalized by a chain transfer agent (CTA) resulting in a macromolecular chain transfer agent (OCS-CTA), which will act as a reactive electrostatic/steric stabilizer. Owing to its UV-sensitivity, OCS-CTA was then used as photo-iniferter to initiate the polymerization of 2-hydroxypropyl methacrylate (HPMA) in aqueous acidic buffer, resulting in OCS-g-PHPMA amphiphilic grafted copolymers which self-assemble into nano-objects. Transmission electron microscopy and light scattering analysis reveal formation of spherical nanostructures.

Applications of Alginate-Based Nanomaterials in Enhancing the Therapeutic Effects of Bee Products.

Since the ancient times, bee products (i.e., honey, propolis, pollen, bee venom, bee bread, and royal jelly) have been considered as natural remedies with therapeutic effects against a number of diseases. The therapeutic pleiotropy of bee products is due to their diverse composition and chemical properties, which is independent on the bee species. This has encouraged researchers to extensively study the therapeutic potentials of these products, especially honey. On the other hand, amid the unprecedented growth in nanotechnology research and applications, nanomaterials with various characteristics have been utilized to improve the therapeutic efficiency of these products. Towards keeping the bee products as natural and non-toxic therapeutics, the green synthesis of nanocarriers loaded with these products or their extracts has received a special attention. Alginate is a naturally produced biopolymer derived from brown algae, the desirable properties of which include biodegradability, biocompatibility, non-toxicity and non-immunogenicity. This review presents an overview of alginates, including their properties, nanoformulations, and pharmaceutical applications, placing a particular emphasis on their applications for the enhancement of the therapeutic effects of bee products. Despite the paucity of studies on fabrication of alginate-based nanomaterials loaded with bee products or their extracts, recent advances in the area of utilizing alginate-based nanomaterials and other types of materials to enhance the therapeutic potentials of bee products are summarized in this work. As the most widespread and well-studied bee products, honey and propolis have garnered a special interest; combining them with alginate-based nanomaterials has led to promising findings, especially for wound healing and skin tissue engineering. Furthermore, future directions are proposed and discussed to encourage researchers to develop alginate-based stingless bee product nanomedicines, and to help in selecting suitable methods for devising nanoformulations based on multi-criteria decision making models. Also, the commercialization prospects of nanocomposites based on alginates and bee products are discussed. In conclusion, preserving original characteristics of the bee products is a critical challenge in developing nano-carrier systems. Alginate-based nanomaterials are well suited for this task because they can be fabricated without the use of harsh conditions, such as shear force and freeze-drying, which are often used for other nano-carriers. Further, conjunction of alginates with natural polymers such as honey does not only combine the medicinal properties of alginates and honey, but it could also enhance the mechanical properties and cell adhesion capacity of alginates.

Pickering emulsions stabilized by biodegradable dextran-based nanoparticles featuring enzyme responsiveness and co-encapsulation of actives.

In this study, Pickering emulsions of dodecane and medium chain triglyceride (MCT) oils were stabilized by simply alkylated-dextran nanoparticles. Our findings show that very little of these bio-friendly nanoparticles is necessary to stabilize Pickering emulsions while providing a high time stability (more than a year at 37 °C). As dextran is known to be cleavable by dextranase enzyme, hydrolysis of the nanoparticles in the presence of dextranase could be achieved. This allowed performing on-demand destabilization of Pickering emulsions. Furthermore, two different fluorescent probes were loaded into the stabilizing particles and the oil droplets respectively, providing a proof of concept for co-encapsulation of actives in advanced delivery applications. Additionally, to a conventional fluorescence probe, quinine, an antimalarial drug was also encapsulated into the nanoparticles.

Dextran-Coated Latex Nanoparticles via Photo-RAFT Mediated Polymerization Induced Self-Assembly.

Polysaccharide coated nanoparticles represent a promising class of environmentally friendly latex to replace those stabilized by small toxic molecular surfactants. We report here an in situ formulation of free-surfactant core/shell nanoparticles latex consisting of dextran-based diblock amphiphilic copolymers. The synthesis of copolymers and the immediate latex formulation were performed directly in water using a photo-initiated reversible addition fragmentation chain transfer-mediated polymerization induced self-assembly strategy. A hydrophilic macromolecular chain transfer-bearing photosensitive thiocarbonylthio group (eDexCTA) was first prepared by a modification of the reducing chain end of dextran in two steps: (i) reductive amination by ethylenediamine in the presence of sodium cyanoborohydride, (ii) then introduction of CTA by amidation reaction. Latex nanoparticles were then formulated in situ by chain-extending eDexCTA using 2-hydroxypropyl methacrylate (HPMA) under 365 nm irradiation, leading to amphiphilic dextran-b-poly(2-hydroxypropyl methacrylate) diblock copolymers (DHX). Solid concentration (SC) and the average degree of polymerization - Xn-- of PHPMA block (X) were varied to investigate their impact on the size and the morphology of latex nanoparticles termed here SCDHX. Light scattering and transmission electron microscopy analysis revealed that SCDHX form exclusively spherical nano-objects. However, the size of nano-objects, ranging from 20 nm to 240 nm, increases according to PHPMA block length.

Direct Access to Polysaccharide-Based Vesicles with a Tunable Membrane Thickness in a Large Concentration Window via Polymerization-Induced Self-Assembly.

Polymersomes are multicompartmental vesicular nano-objects obtained by self-assembly of amphiphilic copolymers. When prepared in the aqueous phase, they are composed of a hydrophobic bilayer enclosing water. Although such fascinating polymeric nano-objects have been widely reported with synthetic block copolymers, their formation from polysaccharide-based copolymers remains a significant challenge. In the present study, the powerful platform technology known as polymerization-induced self-assembly was used to prepare in situ pure vesicles from a polysaccharide-grafted copolymer: dextran-g-poly(2-hydroxypropyl methacrylate) (Dex-g-PHPMA). The growth of the PHPMA grafts was performed with a dextran-based macromolecular chain transfer agent in water at 20 °C using photomediated reversible addition fragmentation chain transfer polymerization at 405 nm. Transmission electron microscopy, cryogenic electron microscopy, small-angle X-ray scattering, atomic force microscopy, and dynamic light scattering revealed that amphiphilic Dex-g-PHPMAX = 100-300 (X is the targeted average degree of polymerization, Xn̅, of each graft at full conversion) exhibit remarkable self-assembly behavior. On the one hand, vesicles were obtained over a wide range of solid concentrations (from 2.5% to 13.5% w/w), which can facilitate posterior targeting of such rare morphology. On the other hand, the extension of Xn̅ induces an increase in the vesicle membrane thickness, rather than a morphological evolution (spherical micelles to cylinders to vesicles).

COVID-19 infection and nanomedicine applications for development of vaccines and therapeutics: An overview and future perspectives based on polymersomes.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which emerged in December 2019 and caused the coronavirus disease 2019 (COVID-19) pandemic, took the world by surprise with an unprecedented public health emergency. Since this pandemic began, extraordinary efforts have been made by scientists to understand the pathogenesis of COVID-19, and to fight the infection by providing various preventive, diagnostic and treatment opportunities based on either novel hypotheses or past experiences. Despite all the achievements, COVID-19 continues to be an accelerating health threat with no specifically approved vaccine or therapy. This review highlights the recent advances in COVID-19 infection, with a particular emphasis on nanomedicine applications that can help in the development of effective vaccines or therapeutics against COVID-19. A novel future perspective has been proposed in this review based on utilizing polymersome nano-objects for effectively suppressing the cytokine storm, which may reduce the severity of COVID-19 infection.

Doxorubicin Intracellular Release Via External UV Irradiation of Dextran-g-poly(o-nitrobenzyl acrylate) Photosensitive Nanoparticles.

In the present study, innovative doxorubicin-loaded nanoparticles (NPs) made of a photosensitive poly(o-nitrobenzyl acrylate) (PNBA) hydrophobic matrix and an hydrophilic dextran (Dex) shell were first formulated by the emulsion-solvent evaporation process. Doxorubicin (DOX), a very well-known anticancer drug, was herein chosen as the model. DOX-loaded NPs were successfully produced by covering the hydrophobic PNBA core with Dex chains either physically adsorbed or covalently linked by changing process parameters as the presence of a catalyst (CuBr or CuSO4/ascorbic acid). It was then proved that the neutralization of DOX optimized drug loading. DOX loading and release were independent of the coverage mechanism if the catalyst used to covalently link the shell to the core was correctly chosen. Second, the kinetics of DOX release were investigated by simple diffusion or light irradiation of the NPs. Experiments showed that less than 20% of DOX was released by simple diffusion after 48 h in PBS or DMEM media when 45% of DOX released after only 30 s of light irradiation of the NPs. Finally, the impact of the phototriggered DOX release on cell viability was investigated on various cell lines [Caco-2, HepG2, HCT-116, and HT-29 cells as well as murine macrophages (RAW 264.7)]. Cellular mortality was evaluated to be dependent on the cell lines tested. Our approach provided an improved DOX release toward the human liver cancer cell line, and a high internalization of the PNBA-based NPs into HepG2 cells was observed using fluorescence microscopy.

Dextran-covered pH-sensitive oily core nanocapsules produced by interfacial Reversible Addition-Fragmentation chain transfer miniemulsion polymerization.

Aiming to prepare oily core pH-sensitive nanocapsules (NCs) for anticancer drugs delivery, the use of a dextran-based transurf (DexN3-τCTAγ) as both stabilizer and macromolecular chain transfer agent in methyl methacrylate/2-(diethylamino)ethyl methacrylate (MMA/DEAEMA) miniemulsion copolymerization was investigated. NCs of about 195 nm with an oily-core of Miglyol 810 (M810) and a dextran coverage covalently linked to the poly(MMA-co-DEAEMA) intern shell have been obtained. Compared to the non-sensitive PMMA-based NCs (prepared in a similar way), these novel objects were shown to swell in acidic media and to trigger Coumarin 1 release in physiological relevant pH range. As a starting point of NCs biological effects, cytotoxicity and NCs-proteins interactions studies were performed with both PMMA and poly(MMA-co-DEAEMA)-based NCs. Finally, free azide functions from dextran-based coverage were successfully exploited to attach fluorescent model dyes to NCs surface. The overall results suggest that this novel NCs platform could be potentially used as drug nanocarriers for intravenous injection.

Synergistic Effects of Nanomedicine Targeting TNFR2 and DNA Demethylation Inhibitor-An Opportunity for Cancer Treatment.

Tumor necrosis factor receptor 2 (TNFR2) is expressed on some tumor cells, such as myeloma, Hodgkin lymphoma, colon cancer and ovarian cancer, as well as immunosuppressive cells. There is increasingly evidence that TNFR2 expression in cancer microenvironment has significant implications in cancer progression, metastasis and immune evasion. Although nanomedicine has been extensively studied as a carrier of cancer immunotherapeutic agents, no study to date has investigated TNFR2-targeting nanomedicine in cancer treatment. From an epigenetic perspective, previous studies indicate that DNA demethylation might be responsible for high expressions of TNFR2 in cancer models. This perspective review discusses a novel therapeutic strategy based on nanomedicine that has the capacity to target TNFR2 along with inhibition of DNA demethylation. This approach may maximize the anti-cancer potential of nanomedicine-based immunotherapy and, consequently, markedly improve the outcomes of the management of patients with malignancy.

Exploring the Contribution of Two Phosphorus-Based Groups to Polymer Flammability via Pyrolysis-Combustion Flow Calorimetry.

From a set of around 100 phosphorus-containing polymers tested in pyrolysis-combustion flow calorimetry, the contributions to flammability of two phosphorus-containing pendant groups (called 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO) and PO3) were calculated using an advanced method previously proposed and validated. The flammability properties include total heat release (THR) and heat release capacity (HRC) measured in standard conditions, i.e., anaerobic pyrolysis and complete combustion. The calculated contributions are in good agreement with the main modes of action of both phosphorus groups, i.e., flame inhibition for DOPO and char promotion for PO3. Moreover, the results provide first conclusions about the cooperative interaction between phosphorus and nitrogen, as well as the influence of the architecture of tested co-polymers.

First multi-reactive polysaccharide-based transurf to produce potentially biocompatible dextran-covered nanocapsules.

A multi-reactive polysaccharide-based transurf (acting both as macro-Chain Transfer Agent and stabilizer) was used to confine RAFT polymerization of methyl methacrylate (MMA) at the oil/water (o/w) miniemulsion interface. Dithiobenzoate groups and hydrophobic aliphatic side chains were introduced onto dextran, conferring it both transfer agent properties and ability to stabilize direct miniemulsion of MMA in the presence of a biocompatible oil, used as co-stabilizer. Because of their amphiphilic character, transurfs were initially adsorbed at the (o/w) interface and their reactive sites mediated RAFT polymerization via the R-group approach. PMMA-grafted dextran glycopolymers were consequently produced at the o/w interface, thus leading to dextran coverage/PMMA shell/oily core nanocapsules (NCs) as evidenced by Cryo-TEM analyses. The influence of dextran-based transurf chemistry and oil amount on MMA RAFT polymerization control was investigated. Positive preliminary results on NCs cytotoxicity suggest the potential of these objects for biomedical applications.

Light-sensitive dextran-covered PNBA nanoparticles to continuously or discontinuously improve the drug release.

In this work, photo-sensitive core/shell nanoparticles (NPs) based on biocompatible dextran-g-poly(o-nitrobenzyl acrylate) copolymers (Dex-g-PNBA), containing dextran as hydrophilic backbone and PNBA as photosensitive grafts, were formulated using two processes. In the first process (nanoprecipitation), NPs were prepared using preformed Dex-g-PNBA copolymers. Using the second process (emulsion/organic solvent evaporation), "clicked" or "unclicked" NPs were obtained carrying out (or not) an interfacial in situ click chemistry, respectively. Two model molecules, Nile Red (NR) and Doxorubicin (DOX), were encapsulated and their controlled release from NPs was investigated under UV irradiations to demonstrate the high potential of such photosensitive NPs in biomedicine applications as drug delivery nanocarriers. According to such irradiations, improved release was easily observed. Release kinetics depended on the formulation process and the NPs core chemistry, but not on the occurrence of the interfacial in situ click chemistry. More interesting, a stepped release of such model molecules may easily be obtained.

Amphiphilic Polysaccharides Acting both as Stabilizers and Surface Modifiers during Emulsification in Microfluidic Flow-Focusing Junction.

A continuous emulsion/solvent diffusion process was designed for the preparation of polysaccharide-covered poly(d,l-lactide) (PLA) microparticles. The emulsification step was carried out in a flow-focusing junction where ethyl acetate containing dissolved PLA was dispersed into an aqueous solution of hydrophobically modified dextran. It was demonstrated that poly(dimethylsiloxane) devices could be used for oil-in-water emulsion preparation provided that the microfluidic devices were preconditioned by simply circulating the aqueous phase containing the amphiphilic polysaccharide during a sufficient time (30 h). The adsorption of the polymers at the surface of the channel walls permitted the wetting by the aqueous phase with a hydrophilic character maintained at least throughout 2 months. The preconditioning time was significantly reduced by pretreating the microfluidic device with piranha solution and KOH solution during 15 min each before the circulation of the aqueous solution of dextran derivative. Dextran-covered PLA microparticle aqueous suspensions were produced with well-controlled size distribution. The suspensions could be lyophilized and reconstituted by retrieving the initial size distribution without adding any cryoprotectant. The reported procedure was used for preparing octyl gallate-loaded PLA microparticles.

Stability of a biodegradable microcarrier surface: physically adsorbed versus chemically linked shells.

Mesenchymal stem cells (MSCs) have gained increasing interest for tissue engineering and cellular therapy. MSC expansion on microcarriers (MCs) in stirred bioreactors has emerged as an attractive method for their scaled up production. Some MCs have been developed based on polyesters as a hydrophobic biodegradable core. However, most of these MCs are formulated by an emulsion/organic solvent evaporation (E/E) process using poly(vinyl alcohol) as a shell steric stabilizer, which is biocompatible but not degradable in vivo. Moreover, in most of these MCs, the polymer shell is only physically adsorbed at the particle surface. To the best of our knowledge, no study deals with the stability of such a shell when the MCs are in contact with competitive surfactants or with proteins contained in the culture medium. In this study, fully in vivo bioresorbable dextran-covered polylactide-based MCs were formulated using an E/E process, which allowed to control their surface chemistry. Different dextran derivatives with alkyne or ammonium groups were firstly synthesised. Then, on the one hand, some MCs (non-clicked MCs) were formulated with a physically adsorbed polysaccharide shell onto the core. On the other hand, the polysaccharide shell was linked to the core via in situ CuAAC click-chemistry carried out during the E/E process (clicked MCs). The stability of such coverage was first studied in the presence of competitive surfactants (sodium dodecyl sulfate-SDS, or proteins contained in the culture medium) using nanoparticles (NPs) exhibiting the same chemical composition (core/shell) as MCs. The results revealed the total desorption of the dextran shell for non-clicked NPs after treatment with SDS or the culture medium, while this shell desorption was greatly decreased for clicked NPs. A qualitative study of this shell stability was finally carried out on MCs formulated using a new fluorescent dextran-based surfactant. The results were in agreement with those observed for NPs, and showed that non-clicked MCs are characterized by poor shell stability in contact with a competitive surfactant, which could be quite an issue during MSC expansion. In contrast, clicked MCs possess better shell stability, which allow a better control of the MC surface chemistry, especially during cell culture.

Light-sensitive dextran-covered PNBA nanoparticles as triggered drug delivery systems: Formulation, characteristics and cytotoxicity.

HYPOTHESIS: For some years, smart nano-objects are one of the main focuses of current research. In the framework of polymeric nanomedicine, o-nitrobenzyl alcohol derivatives lead to light-responsive polymeric materials. At this day, nanomedicine based on polysaccharide/poly(o-nitrobenzyl acrylate) (PNBA) copolymers have never been reported. EXPERIMENTS: For the first time, PNBA core/dextran shell nanoparticles (NPs) were formulated by evaluating two different processes: (i) nanoprecipitation of preformed Dextran-g-PNBA glycopolymers, (ii) emulsion/evaporation using azido-functionalized PNBA and alkynated dextran, carrying out (or not) an interfacial click chemistry reaction. NPs' characterization, colloidal stability in the presence of salts and of an anionic competitive surfactant (SDS) and light-induced disruption were assessed. Finally, the potential use of these NPs as photo-responsive drug delivery systems was investigated by a preliminary in vitro cytotoxicity study using Caco-2 cells. FINDINGS: Whatever the process, the photosensitive property and the colloidal stability of NPs in the presence of salts were proved. However, triazole rings between the dextran shell and the PNBA core avoid the dextran shell desorption in the presence of SDS. NPs' biocompatibility towards Caco-2 was proved and 100% cell viability was still observed after exposure to NPs following by 60 s UV-irradiation.

Nanoparticulate delivery systems for alkyl gallates: Influence of the elaboration process on particle characteristics, drug encapsulation and in-vitro release.

PLA nanoparticles loaded with n-alkyl gallates (AGs) were prepared either by nanoprecipitation (NP) or by O/W emulsion/solvent evaporation (E/SE). A nonionic hydrophobically modified polysaccharide was used for surface coverage and for ensuring colloidal stability. Different parameters were systematically assessed to enhance the drug incorporation, with the aim of obtaining monomodal and narrow particle size distributions. The nanoparticles were characterized by 1H NMR, transmission electron microscopy (TEM) and laser light scattering granulometry. The colloidal stability of suspensions was evaluated after incubation in NaCl solutions and was maintained up to 1M NaCl. The mean particle diameter and the width of size distribution were found very similar for both processes (slightly lower diameters when using E/SE) with various drug loadings. The amount of encapsulated AG by E/SE was about twice that encapsulated by NP. The in-vitro release of AG was evaluated under sink conditions and no burst effect was observed. Release curves were successfully modeled using the Fick diffusion model with a constant diffusion coefficient and assuming non-swellable particles. Diffusion coefficients of AG loaded in nanoparticles prepared by NP were higher than those found in nanoparticles elaborated by E/SE.

Is there a cause-and-effect relationship between physicochemical properties and cell behavior of alginate-based hydrogel obtained after sterilization?

Alginate-based hydrogel scaffolds are widely used in the field of cartilage regeneration and repair. If the effect of autoclaving on the alginate powder is well known, it is not the same for the possible effects of the sterilization UV treatment on the properties of the hydrogel after polymerization. To select an effective sterilization treatment of alginate-based materials, one must find what are inter-relationship between the characteristics (chemical, physical and mechanical) of alginate-based hydrogel during sterilization, and what consequences have affected on cell behavior. In this study, we investigated the influence of UV sterilization treatments (UV-1 and UV-2: 25 and 50min, respectively) and autoclaving to obtain alginate (Alg)/hyaluronic acid (HA) hydrogel, as well as further evaluated the relationship between physicochemical properties and cell behavior of Alg/HA hydrogel after UVs and autoclaving. The physicochemical properties of this mixture at the powder or polymerized states were analyzed using ATR-FTIR, HPLC-SEC, rheological, indentation testing and sterility testing. The cell behaviors of hydrogels were evaluated by cell viability and proliferation, and chondrogenic differentiation. The effects of treatment parameters and their correlation with the others characteristics were determined statistically by Principal Component Analysis (PCA). In this study, we have shown that the cell behavior in alginate-based hydrogels was not only regulated by physicochemical properties (as molar mass or/and viscosity), but also associated with the controlling of sterilization time. It can provide a basis for choosing an effective method of sterilization, which can keep the mechanical or physical-chemical properties of Alg-based hydrogel scaffold and maintain its cytocompatibility and its ability to induce chondrogenesis from mesenchymal stem cells.

Amphiphilic photosensitive dextran-g-poly(o-nitrobenzyl acrylate) glycopolymers.

Among all photosensitive monomers reported in the literature, o-nitrobenzyl acrylate (NBA) was selected in this present study. Two strategies were compared to produce azido-terminated poly(o-nitrobenzyl acrylate) (PNBA) using controlled Single Electron Transfer-Living Radical Polymerization (SET-LRP). In a parallel way, dextran (Dex) was modified by the introduction of several alkynyl-terminated hydrophobic chains. Finally, an Huisgen-type Copper (I)-catalyzed Azide-Alkyne Cycloaddition (CuAAC) click-chemistry was carried out to produce amphiphilic Dex-g-PNBA glycopolymers with different number and length of PNBA grafts. 2D DOSY (1)H NMR was used to prove the formation of such glycopolymers. Preliminary study on Dex-g-PNBA self-assembly was done by measuring the critical water content (CWC) above which Dex-g-PNBA started to auto-organize themselves to produce nano-objects. Finally, under UV irradiation, PNBA grafts turn into poly(acrylic acid) ones giving light-sensitive properties to such amphiphilic Dex-g-PNBA. Such properties were evaluated and compared with those of PNBA.

PLGA-Based Nanoparticles: a Safe and Suitable Delivery Platform for Osteoarticular Pathologies.

PURPOSE: Despite the promising applications of PLGA based particles, studies examining the fate and consequences of these particles after intra-articular administration in the joint are scanty. This study was carried out to evaluate the neutrality of the unloaded delivery system on different articular cell types. To facilitate tracking, we have thus developed a fluorescent core of particles, combined to a hyaluronate shell for cell recognition. METHODS: Fluorescence pictures were taken at time intervals to assess the internalization and the corresponding inflammatory response was monitored by RT-qPCR and biochemical measurements. After NPs pre-treatment, mesenchymal stem cells (MSCs) were cultured into chondrogenic, adipogenic or osteogenic differentiation media, to investigate if NPs exposure interferes with differentiation ability. Finally, intra-articular injections were performed in healthy rat knees and joint's structure analysed by histological studies. RESULTS: Particles were detected in cytoplasm 8 h after exposure. Internalization led to a slight and reversible increase of inflammatory markers, but lower than in inflammatory conditions. We have confirmed particles exposure minimal neutrality on MSCs pluripotency. Histological exams of joint after intra-articular injections do not demonstrate any side effects of NPs. CONCLUSIONS: Our findings suggest that such a delivery platform is well tolerated locally and could be used to deliver active molecules to the joint.

First multi-reactive dextran-based inisurf for atom transfer radical polymerization in miniemulsion.

A multi-reactive polysaccharide-based inisurf (acting both as initiator and stabilizer) has been designed for the first time from dextran with the aim of preparing dextran-covered nanoparticles with covalent linkage between core and coverage. This inisurf was used for polymerizing butyl acrylate in miniemulsion by AGET-ATRP. Both hydrophobic phenoxy groups and initiator groups (bromoisobutyryl ester) were introduced within hydrophilic dextran chain, conferring it amphiphilic and macroinitiator characters. Amphiphilic properties of dextran inisurfs have been evidenced as well as their ability to stabilize the direct miniemulsion of n-butyl acrylate. After optimization of polymerization conditions with model studies, assays were successfully realized with dextran-based inisurfs. Because of their amphiphilic character, inisurfs migrated at oil/water interface and initiated polymerization from bromoisobutyryl ester groups. Therefore graft copolymers were produced at oil/water interface, due to the multifunctional character of these inisurfs and constituted the particle inner core with covalent links to the dextran coverage.