用于组合活性物透皮共递送的环糊精复合物传质体的制备与表征

doi:10.3969/j.issn.1001-1803.2020.08.004

摘要/Abstract

摘要：

以卵磷脂、胆固醇、表面活性剂为壁材制备传质体,通过薄膜水合法分别将苯乙基间苯二酚（PR）与白藜芦醇/羟丙基-β-环糊精（RSV/HP-β-CD）复合物包封在传质体的磷脂双分子层和水性隔室中,获得环糊精复合物传质体（DCTs）。研究了膜软化剂及其添加量、添加方式对DCTs粒径、PDI、Zeta电位、包封率的影响。结果表明,使用0.012 mol/L的T20制得的DCTs粒径较小,为112.43 nm,PDI为0.16,Zeta电位为-34.90 mV,PR与RSV包封率最高,分别为77.07%和60.67%。通过对DCTs体外释放、透皮、细胞毒性及B16-F10细胞内黑色素含量研究,发现DCTs实现了活性物缓释并防止活性物降解,减小了组合活性物透皮递送的渗透性差异,降低了游离活性物的细胞毒性,增强了组合活性物的协同效果,从而减少了B16-F10细胞的黑素生成。

关键词: 美白, 环糊精, 传质体, 苯乙基间苯二酚, 白藜芦醇, 透皮, 共递送

Abstract:

Active-in-cyclodextrin-in-transfersomes （DCTs）, which encapsulated phenylethyl resorcinol （PR） and resveratrol/hydroxypropyl-β-cyclodextrin （RSV/HP-β-CD） inclusion complexes in the phospholipid bilayer and aqueous compartments of the transfersomes, were prepared by thin film hydration using lecithin, cholesterol, and surfactant as encapsulation materials. The effects of edge activator, their concentrations and addition methods on the particle size, PDI, Zeta potential and encapsulation efficiency of DCTs were studied. Results show that the particle size of DCTs prepared by 0.012 mol/L Tween 20 is 112.43 nm, PDI is 0.16, Zeta potential is -34.90 mV, and the high entrapment efficiency of PR and RSV are achieved as 77.07% and 60.67%, respectively. Through in vitro release, transdermal, cytotoxicity and melanin content in B16-F10 cells of DCTs, it was found that DCTs achieved drug sustained release and prevented drug degradation, reduced the permeability difference of transdermal delivery of combination drugs, decreased the cytotoxicity of free drugs, enhanced the synergistic effect of the combination drug, and reduced the melanin content of B16-F10 cells.

Key words: whitening, cyclodextrin, transfersomes, phenylethyl resorcinol, resveratrol, transdermal, co-delivery

中图分类号:

TQ658

佘岚岚,赵炳天,杨成. 用于组合活性物透皮共递送的环糊精复合物传质体的制备与表征[J]. 日用化学工业, 2020, 50(8): 529-535.

SHE Lan-lan,ZHAO Bing-tian,YANG Cheng. Preparation and characterization of active-in-cyclodextrin-in-transfersomes for combined drug transdermal co-delivery[J]. China Surfactant Detergent & Cosmetics, 2020, 50(8): 529-535.

图/表 8

表 1

表 2

图 1

图 2

图 3

图 4

图 5

图 6

参考文献 17

[1]	Wang Y, Hao M M, Sun Y, et al. Synergistic promotion on tyrosinase inhibition by antioxidants[J]. Molecules, 2018,23(1) : 106. doi: 10.3390/molecules23010106
[2]	Fan H, Li Y, Huang Y, et al. Preparation and evaluation of phenylethyl resorcinol liposome[J]. Integrated Ferroelectrics, 2014,151(1) : 89-98. doi: 10.1080/10584587.2014.899873
[3]	Rodríguez-Cabo T, Rodríguez I, Ramil M, et al. Comprehensive evaluation of the photo-transformation routes of trans-resveratrol[J]. Journal of Chromatography A, 2015,1410:129-139. doi: 10.1016/j.chroma.2015.07.088 pmid: 26253832
[4]	Al-Lazikani B, Banerji U, Workman P. Combinatorial drug therapy for cancer in the post-genomic era[J]. Nature Biotechnology, 2012,30(7) : 679. doi: 10.1038/nbt.2284
[5]	Wang A Z, Langer R, Farokhzad O C. Nanoparticle delivery of cancer drugs[J]. Annual Review of Medicine, 2012,63:185-198. doi: 10.1146/annurev-med-040210-162544
[6]	Gadde S. Multi-drug delivery nanocarriers for combination therapy[J]. MedChemComm, 2015,6(11) : 1916-1929. doi: 10.1039/C5MD00365B
[7]	You J O, Guo P, Auguste D T. A drug‐delivery vehicle combining the targeting and thermal ablation of HER2+ breast‐cancer cells with triggered drug release[J]. Angewandte Chemie International Edition, 2013,52(15) : 4141-4146. doi: 10.1002/anie.201209804 pmid: 23494862
[8]	Gidwani B, Vyas A. A comprehensive review on cyclodextrin-based carriers for delivery of chemotherapeutic cytotoxic anticancer drugs[J]. BioMed Research International, 2015,2015(10) : 1-15.
[9]	Anwekar H, Patel S, Singhai A K. Liposome-as drug carriers[J]. International Journal of Pharmacy & Life Sciences, 2011,2(7) : 945-951.
[10]	Amnuaikit T, Limsuwan T, Khongkow P, et al. Vesicular carriers containing phenylethyl resorcinol for topical delivery system; liposomes, transfersomes and invasomes[J]. Asian Journal of Pharmaceutical Sciences, 2018,13(5) : 472-484. doi: 10.1016/j.ajps.2018.02.004 pmid: 32104421
[11]	McCormack B, Gregoriadis G. Drugs-in-cyclodextrins-in liposomes: a novel concept in drug delivery[J]. International Journal of Pharmaceutics, 1994,112(3) : 249-258. doi: 10.1016/0378-5173(94)90361-1
[12]	Cadena P G, Pereira M A, Cordeiro R B S, et al. Nanoencapsulation of quercetin and resveratrol into elastic liposomes[J]. Biochimica et Biophysica Acta (BBA) -Biomembranes, 2013,1828(2) : 309-316. doi: 10.1016/j.bbamem.2012.10.022
[13]	El Zaafarany G M, Awad G A S, Holayel S M, et al. Role of edge activators and surface charge in developing ultradeformable vesicles with enhanced skin delivery[J]. International Journal of Pharmaceutics, 2010,397(1-2) : 164-172. doi: 10.1016/j.ijpharm.2010.06.034 pmid: 20599487
[14]	Wang Jianguo, Jiang Lili, Hui Fei, et al. Study on the interaction of sodium deoxycholate with supported bilayer lipid membrane by electrochemistry method[J]. Acta Chimica Sinica, 2007,65(3) : 239-245.
[15]	Liang Wei. Study on the bufalin liposome[D]. Shanghai: Shanghai Institution of Pharmaceutical Industry, 2000.
[16]	Peralta M F, Guzmán M L, Pérez A P, et al. Liposomes can both enhance or reduce drugs penetration through the skin[J]. Scientific Reports, 2018,8(1) : 13253. doi: 10.1038/s41598-018-31693-y pmid: 30185887
[17]	How C W, Rasedee A, Manickam S, et al. Tamoxifen-loaded nanostructured lipid carrier as a drug delivery system: characterization, stability assessment and cytotoxicity[J]. Colloids and Surfaces B: Biointerfaces, 2013,112:393-399. doi: 10.1016/j.colsurfb.2013.08.009 pmid: 24036474

编码	条件
	ρ（油相）/（g·L^-1）		c（活性物）/（mol·L^-1）		c（膜软化剂）/（mol·L^-1）
	SPC	CHOL	PR	RSV	SDC	T80	T20
S-1	3	0.6	0.007	0.007	0.006 （O）	-	-
S-2	3	0.6	0.007	0.007	0.012 （O）	-	-
T8-1	3	0.6	0.007	0.007	-	0.006 （O）	-
T8-2	3	0.6	0.007	0.007	-	0.012 （O）	-
T2-1	3	0.6	0.007	0.007	-	-	0.006 （O）
T2-2	3	0.6	0.007	0.007	-	-	0.012 （O）
T2-3	3	0.6	0.007	0.007	-	-	0.006 （A）

编码	表征
	粒径/nm	PDI	包封率/%		Zeta电位/mV
	粒径/nm	PDI	PR	RSV	Zeta电位/mV
S-1	145.43±3.35	0.10±0.01	66.88±0.41	44.25±0.90	-56.13±1.20
S-2	110.00±2.70	0.24±0.03	54.17±2.20	9.90±1.94	-25.78±4.52
T8-1	113.93±3.74	0.18±0.01	69.04±0.23	48.79±0.83	-39.32±4.12
T8-2	97.90±2.43	0.18±0.01	72.11±1.06	53.37±2.20	-30.55±3.55
T2-1	112.43±4.73	0.16±0.01	72.17±1.35	53.16±1.95	-34.90±5.94
T2-2	104.17±2.37	0.19±0.01	77.07±1.05	60.67±2.11	-32.74±5.12
T2-3	113.73±2.93	0.14±0.01	70.59±0.81	51.83±1.85	-31.85±3.70