RELEASE OF L-ASCORBIC ACID ENCAPSULATED IN POLY NANOCAPSULES 257 AA entrapped PECA nanocapsules are expected to be used as dermatological or cosmetic products, which can be easily decomposed to sustained release of AA for continual treatment. CONCLUSIONS This study demonstrates that AA could be encapsulated and protected successfully with biodegradable and biocompatible PECA nanocapsules synthesized by the interfacial polymer- ization of W/O microemulsions. The nanocapsule size could be controlled by manipulating surfactant concentration, pH value of the dispersed aqueous phase, and the aqueous fraction of the microemulsions. Low pH value and high fraction of aqueous phase were benefi cial to getting small-sized nanocapsules, while too high or too low surfactant concentration was disadvantageous. The encapsulated AA was protected from oxidation in the core of nanocap- sules and showed superior storage stability in aqueous medium compared to the pure AA. AA could be controlled released from nanocapsules by the enzyme hydrolysis of PECA wall. These fi ndings are important factors for allowing AA-encapsulated PECA nanocapsules to be used as potential dermatological or cosmetic products for continual treatment. ACKNOWLEDGMENTS This work was supported by National Natural Science Foundation of China (20974032) and Shanghai Educational Development Foundation (06OZ005). REFERENCES (1) I. Yamamoto, A. Tai, Y. Fujinami, K. Sasaki, and S. Okazaki, Synthesis and characterization of a series of novel monoacylated ascorbic acid derivatives, 6-O-acyl-2-O-alpha-D-glucopyranosyl-L-ascorbic ac- ids, as skin antioxidants, J. Med. Chem., 45, 462–468 (2002). (2) Y. Horino, S. Takahashi, T. Miura, and Y. Takahashi, Prolonged hypoxia accelerates the posttranscrip- tional process of collagen synthesis in cultured fi broblasts, Life Sci., 71, 3031–3045 (2002). (3) A. Bossi, S. A. Piletsky, E. V. Piletska, P. G. Righetti, and A. P. Turner, An assay for ascorbic acid based on polyaniline-coated microplates, Anal. Chem., 72, 4296–4300 (2000). (4) J. Z. Sun and J. W. Parr, Using nonaqueous emulsions to avoid discoloration reactions, Cosm. Toil., 121, 61–64 (2006). (5) M. Gallarate, M. E. Carlotti, M. Trotta, and S. Bovo, On the stability of ascorbic acid in emulsifi ed systems for topical and cosmetic use, Int. J. Pharm., 188, 233–241 (1999). (6) L. J. Machlin, Hand book of Vitamins, 2nd Ed. (Marcel Dekker Inc., New York, 1991), pp. 508. (7) P. M. Chaudhari, P. V. Kawade, and S. M. Funne, Cosmeceuticals—A review, Int. J. Pharm. Tech., 3, 774–798 (2011). (8) J. K. Rivers, The Role of cosmeceuticals in antiaging therapy, Skin Therapy Lett., 13, 5–9 (2008). (9) K. Morisaki and S. Ozaki, Synthesis of novel vitamin C phosphodiesters: Stability and antioxidant activ- ity, Carbohydr. Res., 286, 123–138 (1996). (10) A. I. Segall and M. A. Moyano, Stability of vitamin C derivatives in topical formulations containing lipoic acid, vitamins A and E, Int. J. Cosmt. Sci., 30, 453–458 (2008). (11) P. Spiclin, M. Gasperlin, and V. Kmetec, Stability of ascorbyl palmitate in topical microemulsion, Int. J. Pharm., 222, 271–279 (2001). (12) R. Austria, A. Semenzato, and A. Bettero, Stability of vitamin C derivatives in solution and topical formulations, J. Pharm. Biomed. Anal., 15, 795–801 (1997). (13) M. Szymula, The infl uence of ascorbic acid on the rheological properties of the microemulsion region of the SDS/pentanol/water system, J. Cosmet. Sci., 56, 267–277 (2005).

JOURNAL OF COSMETIC SCIENCE 258 (14) C. Gregor, Lipid vesicles and other colloids as drug carriers on the skin, Adv. Drug Deliv. Rev., 56, 675–711 (2004). (15) R. H. Muller, R. D. Petersen, A. Hommoss, and J. Pardeike, Nanostructured lipid carriers (NLC) in cosmetic dermal products, Adv. Drug Deliv. Rev., 59, 522–530 (2007). (16) S. A. Wissing and R. H. Müller, Cosmetic applications for solid lipid nanoparticles (SLN), Int. J. Pharm., 254, 65–68 (2003). (17) V. Jenning, A. Gysler, M. Schäfer-Korting, and S. H. Gohla, Vitamin A loaded solid lipid nanoparticles for topical use: Occlusive properties and drug targeting to the upper skin, Eur. J. Pharm. Biopharm., 49, 211–218 (2000). (18) J. H. Yang, S. Y. Lee, Y. S. Han, K. C. Park, and J. H. Choy, Effi cient transdermal penetration and im- proved stability of L-ascorbic acid encapsulated in an inorganic nanocapsule, Bull. Korean Chem. Soc., 24, 499–503 (2003). (19) K. S. Soppimath, T. M. Aminabhavi, A. R. Kulkarni, and W. E. Rudzinski, Biodegradable polymeric nanoparticles as drug delivery, J. Control. Release, 70, 1–20 (2001). (20) C. Vauthier, C. Dubernet, E. Fattal, H. Pinto-Alphandary, and P. Couvreur, Poly(alkylcyanoacrylates) as biodegradable materials for biomedical applications, Adv. Drug. Deliv. Rev., 55, 519–548 (2003). (21) J. Nicolas and P. Couvreur, Synthesis of poly(alkyl cyanoacrylate)-based colloidal nanomedicines, Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol., 1, 111–127 (2009). (22) M. R. Gasco and M. Trotta, Nanoparticles from microemulsions, Int. J. Pharm., 29, 267–268 (1986). (23) S. Watnasirichaikul, N. M. Davies, T. Rades, and I. G. Tucker, Preparation of biodegradable insulin nanocapsules from biocompatible microemulsions, Pharm. Res., 17, 684–689 (2000). (24) G. Cavallaro, M. Fresta, G. Giammona, G. Puglisi, and A. Villari, Entrapment of b-lactams antibiotics in polyethylcyanoacrylate nanoparticles: Studies on the possible in vivo application of this colloidal delivery system, Int. J. Pharm., 111, 31–41 (1994). (25) M. Palumbo, A. Russo, V. Cardile, M. Renis, D. Paolino, G. Puglisi, and M. Fresta, Improved antioxi- dant effect of idebenone-loaded polyethyl-2-cyanoacrylate nanocapsules tested on human fi broblasts, Pharm. Res., 19, 71–78 (2002). (26) M. Fresta, G. Cavallarot, G. Giammonat, E. Wehrlis, and G. Puglisi, Preparation and characterization of polyethyl-2-cyanoacrylate nanocapsules containing antiepileptic drugs, Biomaterials, 17, 751–756 (1996). (27) M. S. el-Samaligy, P. Rohdewald, and H. A. Mahmoud, Polyalkyl cyanoacrylate nanocapsules, J. Pharm. Pharmacol., 38, 216–218 (1986). (28) A. McDowell, B. J. McLeod, T. Rades, and I. G. Tucker, Polymeric nanoparticles as an oral delivery system for biocontrol agents for the brushtail possum (Trichosurus vulpecula), New Zeal. Vet. J., 57, 370– 377 (2009). (29) A. Graf, E. Ablinger, S. Peters, A. Zimmer, S. Hook, and T. Rades, Microemulsions containing lecithin and sugar-based surfactants: Nanoparticle templates for delivery of proteins and peptides, Int. J. Pharm, 350, 351–360 (2008). (30) S. Watnasirichaikul, T. Rades, I. G. Tucker, and N. M. Davies, Effects of formulation variables on char- acteristics of poly(ethylcyanoacrylate) nanocapsules prepared from w/o microemulsions, Int. J. Pharm., 235, 237–246 (2002). (31) S. L. Tong, G. H. Xiang, and W. P. Liu, Determination of ascorbic acid by indirect fl uorimetry, Spectros- copy and Spectral Analysis, 25, 598–600 (2005). (32) V. Lenaerts, P. Couvreur, D. Chr istiaens-Leyh, E. Joiris, and M. Roland, Degradation of poly (isobutyl- cyanoacrylate) nanoparticles, Biomat erials, 5, 65–68 (1984). (33) C. O’Sullivan and C. Birkinshaw, Hydrolysis of poly (n-butylcyanoacrylate) nanoparticles using ester- ase, Polym. Degrad. Stab., 78, 7–15 (2002). (34) D. Scherer, J. Robinson, and J. Kreuter, Infl uence of enzymes on the stability of polycyanoacrylate nanoparticles, Int. J. Pharm., 101, 165–168 (1994). (35) K. Krauel, N. M. Davies, S. Hook, and T. Rades, Using different structure types of microemulsions for the preparation of poly(alkylcyanoacrylate) nanoparticles by interfacial polymerization, J. Control. Re- lease, 106, 76–87 (2005). (36) E. F. Donnelly, Ionic and zwitterionic polymerisation of n-alkyl 2-cyanoacrylates, J. Polym. Sci. Polym. Lett. Edn., 15, 399–405 (1977). (37) D. C. Pepper, Anionic and zwitterionic polymerization of a-cyanoacrylates, J. Polym. Sci. Polym. Symp., 62, 65–77 (1978). (38) R. Davies, D. E. Graham, and B. Vincent, Water-cyclohexane-“Span 80”-“Tween 80” systems: Solution properties and water/oil emulsion formation, J. Colloid Interface Sci., 116, 88–99 (1987).