用共轭亚油酸构筑层状液晶的药物传递系统

doi:10.7503/cjcu20190682

摘要/Abstract

摘要：

在水相中用共轭亚油酸(CLA)及其钠盐(SCL)构筑层状液晶相, 并考察了其药物缓释行为. 借助偏光显微镜并辅以目测确定CLA/SCL/H₂O三元相图中的层状液晶相区, 然后用偏光显微镜、小角X射线散射仪和旋转流变仪获得层状液晶的偏光织构、相参数和流变参数等, 证实其适用于药物传递系统(DDS). 采用透析法研究了负载亲水性药物5-氟尿嘧啶或亲油性药物姜黄素的层状液晶的释药曲线, 结果表明, 该类层状液晶对2种药物均有良好的缓释能力.

关键词: 共轭亚油酸, 层状液晶, 流变性, 药物传递系统

Abstract:

The lamellar liquid crystals in aqueous phase using conjugated linoleic acid(CLA) and its conjugate base sodium conjugated linoleate(SCL) were fabricated, and drug release behavior of the resulted lamellar liquid crystals was investigated. The lamellar liquid crystal phase in the CLA/SCL/H₂O ternary phase diagram was determined by means of polarizing microscopy assisted by visual inspection. The polarized texture, phase parameters and rheological parameters of the lamellar liquid crystals were obtained by polarizing microscope, small-angle X-ray scattering system and rotational rheometer, and the experimental results confirm that the lamellar liquid crystals are suitable for drug delivery system(DDS). The releasing curves of a hydrophilic drug 5-fluorouracil and a lipophilic drug curcumin were measured by dialysis experiments using the drug-loaded lamellar liquid crystals as DDS, and good sustained release abilities for both drugs were provided by the lamellar liquid crystals.

Key words: Conjugated linoleic acid, Lamellar liquid crystal, Rheology, Drug delivery system

中图分类号:

O648

TrendMD:

樊晔, 李倩, 方云, 夏咏梅. 用共轭亚油酸构筑层状液晶的药物传递系统. 高等学校化学学报, 2020, 41(4): 750.

FAN Ye, LI Qian, FANG Yun, XIA Yongmei. Fabrication of Lamellar Liquid Crystals of Conjugated Linoleic Acid as Drug Delivery Systems ^†. Chem. J. Chinese Universities, 2020, 41(4): 750.

图/表 9

Fig.1 Phase diagram of CLA/SCL/H2O system at 25 ℃(A), textures of the lamellar liquid crystals(Lα) obtained by polarizing microscopy before(B) and after(C) ultracentrifugation

Fig.2 SAXS patterns of Lα at 25 ℃ corresponding to different water contents(a1—a3)(A) and CLA contents(b1—b3)(B)

Table 1 Compositions and the related Lα parameters obtained by SAXS

Sample	m(CLA)∶m(SCL)∶m(H₂O)	q₁/nm^-1	q₂/nm^-1	d/nm	Phase
a₁	0.25∶0.75∶0.60	1.338		4.65	Lamellar
a₂	0.25∶0.75∶0.70	1.283	2.528	4.89	Lamellar
a₃	0.25∶0.75∶0.80	1.190	2.373	5.28	Lamellar
b₁	0.20∶0.50∶0.50	1.394	2.736	4.51	Lamellar
b₂	0.30∶0.50∶0.50	1.263	2.482	4.98	Lamellar
b₃	0.40∶0.50∶0.50	1.250	2.484	5.03	Lamellar

Fig.3 Viscosity(η) vs. shear rate(γ˙) of the a series(A) and the b series(B) at 25 ℃

Fig.4 Linear viscoelastic region and critical stress of Lα at 25 ℃(A) Stress sweep of a1 at 1 Hz; (B) complex modulus(G*) vs. shear stress(σ) of the a series; (C) stress sweep of b1 at 1 Hz; (D) complex modulus(G*) vs. shear stress(σ) of the b series.

Table 2 Steady-state and dynamic rheological parameters of Lα at 25 ℃

Sample	η^a/(Pa·s)	σ_c/Pa	G'^b/Pa	G″^c/Pa
a₁	2319	235	7691	714
a₂	2052	195	6061	583
a₃	1780	167	4777	369
b₁	934	178	2543	275
b₂	769	85	2672	217
b₃	617	58	1631	168

Fig.5 Storage modulus(G') and loss modulus(G″) as a function of ω for the a series(A) and the b series(B) at 25 ℃

Fig.6 Effect of temperatures on steady-state and dynamic rheology(A) η vs. γ˙of a1; (B) G' and G″ as a function of ω for a1; (C) η vs. γ˙of b1; (D) G' and G″ as a function of ω for b1.

Fig.7 Cumulative release(CR) rate of 5-FU(A) and curcumin(B) in PBS solution at 37 ℃ and schematic illustration for drug release mechanism of lamellar liquid crystal DDS(C)

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