Synthesis of a Novel Poly(MePEG cyanoacrylate-co-alkyl cyanoacrylate) Amphiphilic Copolymer for Nanoparticle Technology

Abstract

In order to develop “stealth” injectable PEG-coated poly(alkyl cyanoacrylate) (PACA) nanoparticles, a novel poly(MePEG cyanoacrylate-co-alkyl cyanoacrylate) copolymer has been synthetized in a simple way by condensing MePEG cyanoacetate esters with formaldehyde in the presence of dimethylamine. This approach allowed the covalent linkage of PEG moieties to the cyanoacrylate polymer, thus avoiding the risk of desorption of PEG, as in the case of a PEG coating obtained by simple adsorption onto preformed nanoparticles. In addition, the condensation procedure allowed a better control of the polymerization process than in the case of anionic polymerization of alkyl cyanoacrylates. Finally, we have shown that the hydrophobicity of the copolymer can be perfectly modulated by adjusting the MePEG cyanoacetate/alkyl cyanoacetate ratio. Characterization of the copolymer has been performed by NMR, GPC, and FTIR analysis. Monodispersed nanoparticles were easily prepared by nanoprecipitation of this amphiphilic copolymer.

Nanospheres and nanocapsules of amphiphilic copolymers constituted by methoxypolyethylene glycol cyanoacrylate and hexadecyl cyanoacrylate units

“…Poly(MePEGCA-co-HDCA) and poly(hexadecyl cyanoacrylate) (PHDCA) were synthesized as previously reported [11] being 3600 and 5100 g/mol, respectively, the number average molecular weights determined by gel permeation chromatography (GPC). Poly(MePEGCA-co-HDCA) was synthesized from a methoxypolyethylene glycol cyanoacetate to n-hexadecylcyanoacetate ratio of 1:4.…”

“…Particles, spontaneously formed in the mixer chamber, were evacuated by the outlet jet, and then quenched in 25 mL of water under magnetic stirring. Finally, the acetone was evaporated in Valente et al -eXPRESS Polymer Letters Vol.7, No.1 (2013) [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] a rotating device (30 minutes at room temperature) to obtain an aqueous suspension of nanospheres. Nanocapsules were prepared by the same procedure after adding 200 #L of Miglyol 812 (i.e.…”

“…Figures 7a and 7b compare the 1 H NMR spectra of the as-synthesized sample and that degraded up to a weight loss of 67%. The initial sample was characterized by an average molar ratio close to 1:4 between pegylated and hexadecyl (HD) lateral chains, as can be deduced from the areas of the signals at 3.37 and 0.86 ppm assigned to the methyl groups belonging to the two ester moieties [11]. Methylene groups of the main chain and the lateral hexadecyl and PEG groups also appeared well differentiated at 2.37, 1.25 and 3.64 ppm, respectively (Figure 7a).…”

“…These compounds are now prepared mainly by radical copolymerization reactions in monophasic organic solvents like dimethyl formamide or butanone [6,7], or in two-phase solvents where the monomers dissolve each in one of the two phases [8][9][10]. Another method of preparation of cyanoacrylate amphiphilic copolymers is based on the condensation reaction of methoxy polyethylene glycol cyanoacetate and hexadecyl cyanoacetate with formaldehyde in the presence of an organic solvent like methylamine [11]. These methoxy polyethylene glycol cyanoacrylate-co-hexadecyl cyanoacrylate copolymers, abbreviated as poly(MePEGCA-co-HDCA), can be prepared with modulated hydrophobicity/hydro hilicity by adjusting the MePEGCA/HDCA monomer ratio.…”

“…These methoxy polyethylene glycol cyanoacrylate-co-hexadecyl cyanoacrylate copolymers, abbreviated as poly(MePEGCA-co-HDCA), can be prepared with modulated hydrophobicity/hydro hilicity by adjusting the MePEGCA/HDCA monomer ratio. Some previous works focused on the preparation of nanoparticles from poly(MePEGCA-co-HDCA) with a hydrophilic/hydrophobic monomer ratio of 1:4 by nanoprecipitation and emulsion/solvent evaporation methods [11,12]. Monomodal size distributions were obtained with characteristic mean particle sizes ranging between 98 and 199 nm and varying according to polymer concentration and the applied method.…”