Thermo-sensitive amphiphilic copolymers, PVCL-PTrpAMT and PVCL-PVP-PTrpAMT of hydrophilic N-vinylcaprolactam (VCL), N-vinylpyrrolidone (NVP), and hydrophobic N-t-Boc-tryptophanamido-N(-methacryl thioureas (TrpAMT) monomers, were synthesized and characterized by 1 H NMR, UV-spectroscopy, and GPC-MALLS. The cloud point (CP) measurement showed that hydrophobic PTrpAMT and hydrophilic PVP segments significantly altered the phase transition temperature of PVCL with comparable molecular weight in aqueous solution. The CP of PVP-PTrpAMT solution was 38.0-C, lower by 5.0-C than that of unmodified PVCL. In the presence of phosphate buffer saline (PBS), the CP value of the PVCL polymer decreased by $2.0-C in comparison to that of the aqueous solution. Fluorescent spectroscopy and TEM studies revealed that PVCL-PTrpAMT and PVCL-PVP-PTrpAMT self-assembled into the spherical micelles, 30-70 nm in diameter, at concentrations over their CMCs in an aqueous solution. Cytotoxicity tests demonstrated that the PVCL copolymers were not harmful to cell viability, which may favor the use of the copolymers as potential thermo-sensitive polymers in pharmaceutical applications. Copyright ß 2009 John Wiley & Sons, Ltd.Keywords: amphiphiles; self-assembly; solution properties; thermo-sensitive; N-vinylcaprolactam
INTRODUCTIONThermo-responsive amphiphilic copolymers have recently attracted extensive attention because of both their intrinsic properties [1][2][3] and their wide range of potential applications in medicine, [4] biotechnology, [5] ecology, [6] and pharmacology. [7] An aqueous solution of this type of polymer is characterized by a phase separation upon heating, and the system exhibits a lower critical solution temperature (LCST). [8,9] At a low temperature, the solution is homogeneous, but when the temperature exceeds a certain value called the cloud point (CP) of the mixture, a macroscopic phase separation occurs. The LCST corresponds to the minimum of the phase separation curve. [10,11] Belonging to the category of thermo-sensitive polymers, poly(N-vinylcaprolactam) (PVCL) has recently attracted a great deal of interest. [12][13][14][15] PVCL is a well-known polymer exhibiting the LCST behavior. It shows a dissolution/precipitation transition in water at temperatures close to body temperature. [16] Also, PVCL is stable against hydrolysis, non-toxic, and biocompatible. [17] These properties make it an interesting candidate for biomedical applications. [5,18] To further modulate the features of PVCL aqueous solutions, PVCL has been modified via copolymerization with N-vinylpyrrolidone (NVP), [19] methacrylic acid, [20] N-vinylimidazole, [21] and alkyl acrylate derivations labeled with pyrene or naphthalene, [22] as well as via grafting with PEO as an effective stabilizing agent. [23] The studies of the properties of hydrophobically modified PVCL polymers suggest that the polymers can associate to form polymeric micelles via hydrophobic interactions in aqueous solution below the LCST. [22,24] But to the best of our knowledge, the ...
