Poly(N-Vinylcaprolactam) Stabilized with 2-Bromo-2-nitropropane-1,3-diol

Abstract

In recent years there have been extensive investigation into various means of linking biologically active substances to polymers. The potential synthetic polymeric carriers include poly(vinyl lactams) such as poly(vinyl pyrrolidone) (and its copolymers with acrolein, acrylamide, and acrylic acid) and poly(N-vinylcaprolactam) (PNVC), which possess many useful and even unique properties. In particular, these polymers are highly hydrophilic, well soluble, and nontoxic and exhibit pronounced complex-forming and good adhesion properties. However, these materials (in particular, PNVC) are still insufficiently studied from the standpoint of ability to serve as biologically active matrices [1 – 3]. Taking into account that PNVC can be used for obtaining granules with incorporated biologically active substances by merely adding an aqueous PNVC solution with encapsulated substance to a stabilizer solution, we have studied the possibility to stabilize PNVC with the aid of 2-bromo-2-nitropropane-1,3-diol (bronopol). The aim of this study was to obtain complex proteolytic enzyme preparations possessing antimicrobial activity. A distinctive feature of bronopol as a preservative is the high antimicrobial activity with respect to Ps. aeruginosa and other Pseudomonases species, which are rather weakly inhibited by most antimicrobial drugs that are toxic to warm-blooded mammals. Another useful property is the absence of negative action upon the natural microflora of skin and less pronounced cytotoxic properties as compared to those of, for example, chlorohexin [4]. Bronopol is widely used for imparting antiseptic properties to numerous products such as toothpaste and mouthwash elixirs, antacids (Almagel, etc.), injection solutions, eye drops, contact lenses, cosmetics, and hygienic preparations for children [5]. At the same time, bronopol is insufficiently stable in aqueous solutions, retaining its properties only in the cold and in acid media. Increasing pH and temperature leads to decomposition, which usually proceeds by detachment of formaldehyde. The process of thermal deposition of PNVC in bronopol solutions leads to the formation of a polymeric precipitate. Depending on the solution concentration, granules formed in this system either retain (for a bronopol concentration about 4%) or lose (0.5 – 3%) their shape upon complete drying. According to the results of analyses, dry PNVC preparation granulated in a 4% bronopol solution contained 20% of bronopol. Investigation of the effect of temperature on the stabilization of PNVC by bromopol showed that the maximum inclusion of bronopol into the polymer matrix was observed at 40°C, that is, in the temperature range of thermal deposition of PNVC (Table 1). The influence of pH on the stabilization of PNVC by bromopol was studied in a Na-phosphate buffer. It was found that the inclusion of bronopol increased above pH 5.0 – 6.0 (Table 2). The bioaccessibility of bronopol encapsulated in PNVC, as compared to that in an aqueous solution of the same concentration, was studied by the method of dialysis through a