参考文献:1. Alamanosand Y, Drosos AA. Epidemiology of adult rheumatoid arthritis. Autoimmun Rev. 2005;4:130鈥?. CrossRef 2. Eureniusand E, Stenstrom CH. Physical activity, physical fitness, and general health perception among individuals with rheumatoid arthritis. Arthritis Rheum. 2005;53:48鈥?5. CrossRef 3. Rahmeand E, Bernatsky S. NSAIDs and risk of lower gastrointestinal bleeding. Lancet. 2010;376:146鈥?. CrossRef 4. Sostres C, Gargallo CJ, Arroyo MT, Lanas A. Adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs, aspirin and coxibs) on upper gastrointestinal tract. Best Pract Res Clin Gastroenterol. 2010;24:121鈥?2. CrossRef 5. Farkouhand ME, Greenberg BP. An evidence-based review of the cardiovascular risks of nonsteroidal anti-inflammatory drugs. Am J Cardiol. 2009;103:1227鈥?7. CrossRef 6. McGettiganand P, Henry D. Cardiovascular risk and inhibition of cyclooxygenase: a systematic review of the observational studies of selective and nonselective inhibitors of cyclooxygenase 2. JAMA J Am Med Assoc. 2006;296:1633鈥?4. CrossRef 7. Ray WA, Stein CM, Daugherty JR, Hall K, Arbogast PG, Griffin MR. COX-2 selective non-steroidal anti-inflammatory drugs and risk of serious coronary heart disease. Lancet. 2002;360:1071鈥?. CrossRef 8. Rainsford KD. Profile and mechanisms of gastrointestinal and other side effects of nonsteroidal anti-inflammatory drugs (NSAIDs). Am J Med. 1999;107:27S鈥?5. discussion 35S鈥?6S. CrossRef 9. Huang L, Mackenzie G, Ouyang N, Sun Y, Xie G, Johnson F, / et al. The novel phospho-non-steroidal anti-inflammatory drugs, OXT-328, MDC-22 and MDC-917, inhibit adjuvant-induced arthritis in rats. Br J Pharmacol. 2011;162:1521鈥?3. CrossRef 10. Huang L, Zhu C, Sun Y, Xie G, Mackenzie GG, Qiao G, / et al. Phospho-sulindac (OXT-922) inhibits the growth of human colon cancer cell lines: a redox/polyamine-dependent effect. Carcinogenesis. 2010;31:1982鈥?0. CrossRef 11. Mackenzie GG, Sun Y, Huang L, Xie G, Ouyang N, Gupta RC, / et al. Phospho-sulindac (OXT-328), a novel sulindac derivative, is safe and effective in colon cancer prevention in mice. Gastroenterology. 2010;139:1320鈥?2. CrossRef 12. Wong CC, Cheng KW, Xie G, Zhou D, Zhu CH, Constantinides PP, / et al. Carboxylesterases 1 and 2 hydrolyze phospho-nonsteroidal anti-inflammatory drugs: relevance to their pharmacological activity. J Pharmacol Exp Ther. 2012;340:422鈥?2. CrossRef 13. Xie G, Nie T, Mackenzie GG, Sun Y, Huang L, Ouyang N, / et al. The metabolism and pharmacokinetics of phospho-sulindac (OXT-328) and the effect of difluoromethylornithine. Br J Pharmacol. 2012;165:2152鈥?6. CrossRef 14. Kalia YN, Naik A, Garrison J, Guy RH. Iontophoretic drug delivery. Adv Drug Deliv Rev. 2004;56:619鈥?8. CrossRef 15. Naik A, Kalia YN, Guy RH. Transdermal drug delivery: overcoming the skin鈥檚 barrier function. Pharm Sci Technol Today. 2000;3:318鈥?6. CrossRef 16. Prausnitz MR, Mitragotri S, Langer R. Current status and future potential of transdermal drug delivery. Nat Rev Drug Discov. 2004;3:115鈥?4. CrossRef 17. Rhee YS, Chang SY, Park CW, Chi SC, Park ES. Optimization of ibuprofen gel formulations using experimental design technique for enhanced transdermal penetration. Int J Pharm. 2008;364:14鈥?0. CrossRef 18. Farringtonand K, Regan F. Molecularly imprinted sol gel for ibuprofen: an analytical study of the factors influencing selectivity. Talanta. 2009;78:653鈥?. CrossRef 19. Ustundag Okur N, Apaydin S, Karabay Yavasoglu NU, Yavasoglu A, Karasulu HY. Evaluation of skin permeation and anti-inflammatory and analgesic effects of new naproxen microemulsion formulations. Int J Pharm. 2011;416:136鈥?4. 20. Huang ZJ, Hsu E, Li HC, Rosner AL, Rupert RL, Song XJ. Topical application of compound Ibuprofen suppresses pain by inhibiting sensory neuron hyperexcitability and neuroinflammation in a rat model of intervertebral foramen inflammation. J Pain Off J Am Pain Soc. 2011;12:141鈥?2. CrossRef 21. Taboada M, Santen R, Lima J, Hossain J, Singh R, Klein KO, / et al. Pharmacokinetics and pharmacodynamics of oral and transdermal 17beta estradiol in girls with Turner syndrome. J Clin Endocrinol Metab. 2011;96:3502鈥?0. CrossRef 22. Yerramsetty KM, Rachakonda VK, Neely BJ, Madihally SV, Gasem KA. Effect of different enhancers on the transdermal permeation of insulin analog. Int J Pharm. 2010;398:83鈥?2. CrossRef 23. Pillaiand O, Panchagnula R. Transdermal delivery of insulin from poloxamer gel: / ex vivo and / in vivo skin permeation studies in rat using iontophoresis and chemical enhancers. J Control Release Off J Control Release Soc. 2003;89:127鈥?0. CrossRef 24. Wan DH, Zheng O, Zhou Y, Wu LY. Solubilization of Ibuprofen in Pluronic Block Copolymer F127 Micelles. Acta Phys-Chim Sin. 2010;26:3243鈥?. 25. Foster B, Cosgrove T, Hammouda B. Pluronic triblock copolymer systems and their interactions with ibuprofen. Langmuir. 2009;25:6760鈥?. CrossRef 26. Wanka G, Hoffmann H, Ulbricht W. Phase-diagrams and aggregation behavior of poly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) triblock copolymers in aqueous-solutions. Macromolecules. 1994;27:4145鈥?9. CrossRef 27. Alexandridis P. Poly(ethylene oxide) poly(propylene oxide) block copolymer surfactants. Curr Opin Colloid Interface Sci. 1997;2:478鈥?9. CrossRef 28. Cabana A, AitKadi A, Juhasz J. Study of the gelation process of polyethylene oxide(a) polypropylene oxide(b) polyethylene oxide(a) copolymer (Poloxamer 407) aqueous solutions. J Colloid Interface Sci. 1997;190:307鈥?2. CrossRef 29. Anderson BC, Pandit NK, Mallapragada SK. Understanding drug release from poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) gels. J Control Release Off J Control Release Soc. 2001;70:157鈥?7. CrossRef 30. Cheng KW, Mattheolabakis G, Wong CC, Ouyang N, Huang L, Constantinides PP, / et al. Topical phospho-sulindac (OXT-328) is effective in the treatment of non-melanoma skin cancer. Int J Oncol. 2012;41:1199鈥?203. 31. Schmolka IR. Artificial skin. I. Preparation and properties of pluronic F-127 gels for treatment of burns. J Biomed Mater Res. 1972;6:571鈥?2. CrossRef 32. Whiteley PE, Dalrymple SA. Models of inflammation: adjuvant-induced arthritis in the rat. Curr Protoc Pharmacol. 2001;Chapter 5:Unit5 5. 33. Bendele A. Animal models of rheumatoid arthritis. J Musculoskelet Neuronal Interact. 2001;1:377鈥?5. 34. Bendele A, McComb J, Gould T, McAbee T, Sennello G, Chlipala E, / et al. Animal models of arthritis: relevance to human disease. Toxicol Pathol. 1999;27:134鈥?2. CrossRef 35. Ahnand KS, Aggarwal BB. Transcription factor NF-kappaB: a sensor for smoke and stress signals. Ann N Y Acad Sci. 2005;1056:218鈥?3. CrossRef 36. Mattheolabakis G, Lagoumintzis G, Panagi Z, Papadimitriou E, Partidos CD, Avgoustakis K. Transcutaneous delivery of a nanoencapsulated antigen: induction of immune responses. Int J Pharm. 2010;385:187鈥?3. CrossRef 37. Lioneand A, Scialli AR. The developmental toxicity of indomethacin and sulindac. Reprod Toxicol. 1995;9:7鈥?0. CrossRef 38. Roman-Blasand JA, Jimenez SA. NF-kappa B as a potential therapeutic target in osteoarthritis and rheumatoid arthritis. Osteoarthr Cartil. 2006;14:839鈥?8. CrossRef 39. Anderson GD, Hauser SD, McGarity KL, Bremer ME, Isakson PC, Gregory SA. Selective inhibition of cyclooxygenase (COX)-2 reverses inflammation and expression of COX-2 and interleukin 6 in rat adjuvant arthritis. J Clin Invest. 1996;97:2672鈥?. CrossRef