Poly(n-butyl cyanoacrylate) nanoparticles via miniemulsion polymerization. 2. PEG-based surfactants

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Abstract

This study aimed at synthesizing PEG-coated poly(n-butyl cyanoacrylate) nanoparticles by miniemulsion polymerization. Despite the high reactivity of butyl cyanoacrylate, nanoparticles were successfully obtained by miniemulsion polymerization of butyl cyanoacrylate-in-water emulsions stabilized by three PEG-based surfactants: Brij®78, Brij®700, and Tween®80. Their physico-chemical properties were thoroughly investigated as a function of surfactant structure and concentration and discussed on the basis of results obtained from interfacial tension measurements (dodecane–water). Results clearly showed the influence of the length of the PEG part of the surfactant on the final properties of the particles.

Introduction

Over the past decades, there has been considerable interest in developing biodegradable nanoparticles as effective drug delivery systems [1], [2]. However, many studies have highlighted their rapid removal following injection into the bloodstream, resulting from their interactions with the mononuclear phagocyte system (MPS) or with the complement system [3], [4], [5]. It is now well known that it is possible to modulate the biodistribution of these nanoparticles by changing appropriately some of their physico-chemical properties, such as size and surface characteristics [6], [7]. In the case of poly(alkyl cyanoacrylate) nanoparticles, it was suggested to reduce the particle size and/or modify the surface of the nanoparticles by highly hydrophilic polymers avoiding opsonins adsorption on particles that makes them recognizable to the macrophages of MPS [8]. Polyethylene glycol (PEG) is one of the most studied hydrophilic polymer used to modify surface properties of nanoparticulate carriers; leading to so-called “stealth nanoparticles” [9], [10].

Poly(alkyl cyanoacrylate) nanoparticles have been extensively studied for drug delivery applications. A large number of different compounds have been entrapped in such nanoparticles, either in the core of the nanoparticles (Doxorubicin [11], Ftorafur [12]) or at their surface (Amoxicillin [13], Methotrexate [14]). PEG-coated poly(alkyl cyanoacrylate) nanoparticles are essentially prepared by two techniques. The first one involves anionic polymerization of alkyl cyanoacrylate in the presence of PEG [13], [15], [16]. The second one requires the synthesis of a PEG-poly(cyanoacrylate) copolymer for the formation of PEG-coated nanoparticles by nanoprecipitation [17], [18], [19]. In both cases, the final solid content of the suspensions is rather low.

More recently, a few authors explored with success the possibilities offered by the miniemulsion polymerization technique. Miniemulsions are relatively stable emulsions of oil nanodroplets in water, prepared via intense shearing of a mixture of monomer, water, a stabilizer and a highly water insoluble compound, the so-called hydrophobe [20], [21], [22]. This compound suppresses the mass exchange between the oil droplets, the Ostwald ripening, and the stabilizer avoids droplets coalescence. Taking advantage of the high stability of miniemulsions, they obtained poly(alkyl cyanoacrylate) nanoparticles dispersions with solid content up to 10% [23], [24], [25]. However, little attention was paid on the influence of the nature of the surfactant on the final physico-chemical properties of the nanoparticles.

This study aimed at synthesizing PEG-coated poly(n-butyl cyanoacrylate) plain nanoparticles via miniemulsion polymerization stabilized by PEG-based surfactants with different PEG chain length and number: Brij®78, Brij®700, and Tween®80 (Table 1). Despite the high reactivity of butyl cyanoacrylate, PEG-coated nanoparticles were successfully synthesized. Their physico-chemical properties (particle diameter, surface coverage, and hydrophilic layer thickness) were thoroughly investigated as a function of surfactant structure and concentration and discussed on the basis of results obtained from interfacial tension measurements (dodecane–water).

Section snippets

Materials

n-Butyl cyanoacrylate (BCA) was obtained from Loctite (Ireland). Hydrochloric acid (1N) and dodecane (≥99%) were purchased from Aldrich. Brij®78, Brij®700, Tween®80 and sodium dodecyl sulfate (SDS) were purchased from Sigma. MilliQ water was used for all the experiments.

Dynamic interfacial tension

Dynamic tensiometer from IT Concept (Longessaigne, France) was used. For the measurement of dynamic surface tension, an oil bubble was formed in the aqueous solution. The shape of the bubble was followed by a CCD camera and the

Characteristics of the PEG-derivatives used

Three PEG-based surfactants, with different PEG chain length and number, were used to stabilize miniemulsion polymerization of BCA: Brij®78, Brij®700, and Tween®80 (Table 1). Brij®78, Brij®700 are linear compounds with respectively 20 and 100 ethylene oxide (EO) units, whereas Tween®80 has a branched structure with 3 PEG chains. Its total number of EO units is 20.

In a first approach, the interfacial tension (aqueous solution/dodecane) was measured with a dynamic tensiometer as a function of

Conclusion

This study aimed at synthesising PEG-coated poly(n-butyl cyanoacrylate) nanoparticles with controlled surface properties. Despite the high reactivity of n-butyl cyanoacrylate, nanoparticles were successfully obtained by miniemulsion polymerization of n-butyl cyanoacrylate in water emulsions stabilized by three amphiphilic derivatives of PEG: Brij®78, Brij®700 and Tween®80. Their physico-chemical properties were thoroughly investigated as a function of surfactant structure and concentration.

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