Kikwai Loice, Babu R J, Kanikkannan Narayanasamy, Singh Mandip
Division of Pharmaceutics, College of Pharmacy and Pharmaceutical Sciences, Florida A and M University, Tallahassee, Florida, USA.
J Pharm Pharmacol. 2004 Jan;56(1):19-25. doi: 10.1111/j.2042-7158.2004.tb02573.x.
Substance P is readily expressed in skin inflammatory disorders such as psoriasis and contact dermatitis. Spantide II is a peptide (MW 1668.76) that specifically binds to neurokinin-1 receptor (NKR-1) and blocks inflammation associated with substance P. The anti-inflammatory property of Spantide II makes it a suitable candidate to be studied as a topical formulation for the treatment of dermal inflammatory disorders. The objective of this study was to investigate the influence of pH, temperature, salt concentration and concentration on the aqueous stability of Spantide II. The stability of Spantide II was also assessed by circular dichroic (CD) spectroscopy and mass spectrometry (MS). The influence of various dermatological vehicles (ethanol, Transcutol, propylene glycol, N-methyl-2-pyrrolidone (NMP), ethyl oleate, isopropyl myristate and laurogylcol FCC (LFCC)) on the stability of Spantide II was investigated. A precise high-performance liquid chromatography (HPLC) assay was developed for analysis of Spantide II. At higher temperature (40 degrees C) the stability of Spantide II decreased with increase in pH (P < 0.05). Change in salt concentration did not appreciably affect the stability of Spantide II (P > 0.05). The concentration of Spantide II in the solution had no significant influence on its stability (P > 0.05). CD spectroscopy studies showed that Spantide II has a relatively stable alpha-helix structure in the liquid state. The stability of Spantide II was affected by the type of vehicle used in the study (P < 0.01) at different temperatures (P < 0.05). Spantide II at high temperature undergoes lysine-proline diketopiperazine degradation as evident in MS data. Spantide II was relatively more stable in ethyl oleate-ethanol, ethanol-water, ethanol and N-methyl-2-pyrrolidone. The results of this study indicate that ethyl oleate-ethanol (1:1) and ethanol-water (1:1) could be used as potential vehicles in the development of topical formulations of Spantide II.
P物质在诸如牛皮癣和接触性皮炎等皮肤炎症性疾病中易于表达。Spantide II是一种肽（分子量1668.76），它特异性结合神经激肽-1受体（NKR-1）并阻断与P物质相关的炎症。Spantide II的抗炎特性使其成为作为治疗皮肤炎症性疾病的局部制剂进行研究的合适候选物。本研究的目的是研究pH、温度、盐浓度和浓度对Spantide II水溶液稳定性的影响。还通过圆二色（CD）光谱和质谱（MS）评估了Spantide II的稳定性。研究了各种皮肤科载体（乙醇、二乙二醇单乙醚、丙二醇、N-甲基-吡咯烷酮（NMP）、油酸乙酯、肉豆蔻酸异丙酯和月桂醇聚醚FCC（LFCC））对Spantide II稳定性的影响。开发了一种精确的高效液相色谱（HPLC）分析法用于分析Spantide II。在较高温度（40℃）下，Spantide II的稳定性随pH升高而降低（P<0.05）。盐浓度的变化对Spantide II的稳定性没有明显影响（P>0.05）。溶液中Spantide II的浓度对其稳定性没有显著影响（P>0.05）。CD光谱研究表明，Spantide II在液态时有相对稳定的α-螺旋结构。在不同温度下（P<0.05），Spantide II的稳定性受研究中使用的载体类型影响（P<0.01）。如MS数据所示，高温下的Spantide II会发生赖氨酸-脯氨酸二酮哌嗪降解。Spantide II在油酸乙酯-乙醇、乙醇-水、乙醇和N-甲基-2-吡咯烷酮中相对更稳定。本研究结果表明，油酸乙酯-乙醇（1:1）和乙醇-水（1:1）可作为开发Spantide II局部制剂的潜在载体。
