J. Cosmet. Sci., 61, 421–437 (November/December 2010) 421 Stable environmentally sensitive cationic hydrogels for controlled delivery applications NAMITA DEO, S. RUETSCH, K.R. RAMAPRASAD, and Y. KAMATH, TRI/Princeton, 601 Prospect Avenue, P. O. Box 625, Princeton, NJ 08542. Accepted for publication July 26, 2010. Synopsis New thermosensitive, cationic hydrogels were synthesized by the dispersion copolymerization of N-isopro- pylacrylamide (NIPAM) and (3-acrylamidopropyl)trimethylammonium chloride (AAPTAC). In the poly- merization protocol, an amide-based comonomer, (3-acrylamidopropyl)trimethylammonium chloride, was reacted as a new alternative monomer for introducing positive charges into the thermosensitive hydrogel. The hydrogels were synthesized without making any pH adjustment in the aqueous medium. These hydrogel particles exhibited colloidal stability in the pH range of 1.5 to 11.0, while similar cationic hydrogels were reported to be unstable at pHs higher than 6. The stronger cationic character of the selected comonomer provided higher colloidal stability to the poly(NIPAM-co-AAPTAC) hydrogels. Furthermore, these hydro- gels displayed sensitivity towards temperature, pH, and salt concentration. Interestingly, the particle size of hydrogels was found to be decreased signifi cantly with an increase in temperature and salt concentration. In addition, using pyrene fl uorescence spectroscopy, it was established that the hydrophobicity/hydrophilicity of the hydrogel particles was largely controlled by both pH and temperature. The thermosensitive hydrogels reported in this paper may be suitable for delivering different actives for cosmetic and medical applications. Although direct application of these hydrogel particles in cosmetics has not been shown at this stage, the methodology of making them and controlling their absorption and release properties as a function of temper- ature and pH has been demonstrated. Furthermore, these hydrogels may also have applications in scavenging organic and inorganic toxics. INTRODUCTION Environmentally responsive hydrogels have been subjects of great interest for the past few years due to their versatile applications. Such hydrogels are termed “intelligent” or “smart” since their properties enable them to react in a specifi c way to changes in the environment. Thermo-responsive synthetic hydrogels, exhibiting a lower critical solution temperature (LCST) in aqueous solution over a narrow temperature range, have received much attention recently. They swell and expand below the LCST but deswell and shrink above that temperature. The major cause for the LCST phenome- non is the entropy-driven hydrophobic interaction of polymer chains that have a delicate Address all correspondence to Namita Deo at ndeo@triprinceton.com, nd157@yahoo.com

JOURNAL OF COSMETIC SCIENCE 422 balance of hydrophilic and hydrophobic moieties in the structure. Among them, the most extensively studied thermosensitive polymer is poly-N-isopropylacrylamide (PNIPAM), which exhibits a lower critical solution temperature (LCST) of 34°C (1,2). Chemically cross-linked PNIPAM hydrogels reveal a drastic particle size decrease upon heating in aqueous solution. The responsive characteristics of these hydrogels have been modifi ed further using both co-polymerization and advanced polymer ar- chitecture (3,4). Cationically charged poly(NIPAM) hydrogels attracted signifi cant attention particularly as carriers for affi nity chromatography and diagnostic test applications (5–7). The phase transition behavior of monodisperse cationically charged poly(NIPAM) hydrogel parti- cles was investigated by fl uorescence spectroscopy (8). Poly(NIPAM) hydrogels with amino groups were used as carriers for the immobilization of oligodeoxyribonucleotides for the enhancement of diagnostic test sensitivity (9). Cationic poly(NIPAM) hydrogels and their magnetic forms were successfully tried as support materials for the specifi c ex- traction of nucleic acids (10,11). The adsorption of HIV-1 capsid p24 protein onto ther- mosensitive and cationic core shell poly(styrene)-poly(NIPAM) particles was investigated by Duracher et al. (12). The synthesis and colloidal properties of NIPAM-dimethylamino- ethyl methacrylate copolymer hydrogels were investigated by Zha et al. (13–14) and by Zhang et al. (15). In the past few years, 4-vinylpridine, vinylimidazole, and n-vinylform- amide were proposed as comonomers in the synthesis of NIPAM-based cationic hydrogels (16–25). In the synthesis of poly(NIPAM)-based cationic hydrogels, mostly methacrylate-based comonomers (i.e., aminoethyl methacrylate or dimethylaminoethyl methacrylate) have been used to incorporate cationic groups into the structure of poly(NIPAM) particles (9–16). In this study, a thermosensitive cationic hydrogel was fi rst synthesized by using an amide-based cationic comonomer, (3-acrylamidopropyl)trimethylammonium chlo- ride. Responses of these hydrogels to various stimuli, such as temperature, pH, and salt and urea concentration, were explored using AFM, SEM, light-scattering, fl uorescence, and UV-visible and FTIR spectrophotometric investigations. For the delivery of a cosmetically active ingredient via encapsulation in a hydrogel nanoparticle, there are two basic requirements. One of these is a cationic charge that will help the particles to adsorb on the surface of hair, and the second requirement is the diffusion of the active out of the particle by changing the environmental conditions, such as an increase in temperature. For a rinse-off system, such as a shampoo or a con- ditioner, the particle size is critical. In a rinse-off situation the particles adsorbed on hair experience the force of adhesion between the particle and the hair surface and the viscous drag of the wash water fl owing through the hair assembly in contact with the par- ticles. Viscous drag is proportional to the surface area of the particle (hence the square of the particle diameter). It is very likely that the larger particles will be washed off the surface, leaving no residue. Therefore, it is imperative that the particle size be in the range of about 500 nm. This is based on the unpublished work done at TRI/ Princeton on the deposition of anionic polystyrene particles on cationically modifi ed hair surface. When acrylamide derivatives are used, toxicity of the monomer becomes a question. Since the monomer is soluble in water, it can be washed away easily. This is the reason why acrylamide polymers are often used in water purifi cation.