Resveratrol-Loaded Lipid Nanocarriers Are Internalized By Endocytosis in Yeast

被引:13
作者
Barbosa, Celia [1 ]
Santos-Pereira, Catia [1 ,2 ]
Soares, Ines [1 ]
Martins, Viviana [1 ,3 ]
Terra-Matos, Joana [1 ]
Corte-Real, Manuela [1 ]
Lucio, Marlene [4 ]
Real Oliveira, M. E. C. D. [4 ]
Geros, Hernani [1 ,2 ,3 ]
机构
[1] Univ Minho, Dept Biol, Ctr Mol & Environm Biol CBMA, Campus Gualtar, P-4710057 Braga, Portugal
[2] Univ Minho, Dept Biol Engn, Ctr Biol Engn CEB, Campus Gualtar, P-4710057 Braga, Portugal
[3] Univ Tras Os Montes & Alto Douro, Ctr Res & Technol Agroenvironm & Biol Sci CITAB, P-5000801 Vila Real, Portugal
[4] Univ Minho, Dept Phys, Ctr Phys CFUM, Campus Gualtar, P-4710057 Braga, Portugal
来源
JOURNAL OF NATURAL PRODUCTS | 2019年 / 82卷 / 05期
关键词
CHEMOPREVENTIVE PROPERTIES; DRUG-DELIVERY; LIPOSOMES; PERMEABILITY; APOPTOSIS; SYSTEMS; CELLS; BIOAVAILABILITY; NANOPARTICLES; ENCAPSULATION;
D O I
10.1021/acs.jnatprod.8b01003
中图分类号
Q94 [植物学];
学科分类号
071001 ;
摘要
Different positive pharmacological effects have been attributed to the natural product resveratrol (RSV), including antioxidant, antiaging, and cancer chemopreventive properties. However, its low bioavailability and rapid metabolic degradation has led to the suspicion that many of the biological activities of this compound observed in vitro may not be attainable in humans. To improve its bioavailability and pharmacokinetic profile, attempts have been made to encapsulate RSV into lipid-based nanocarrier systems. Here, the dioctadecyldimethylammonium bromide (DODAB):monoolein (MO) liposomal system (1:2) loaded with RSV revealed appropriate characteristics for drug release purposes: reduced size for cellular uptake (157 +/- 23 nm), stability up to 80 days, positive surface charge (zeta approximate to +40 mV), and a controlled biphasic release of RSV from the lipid nanocarriers over a period of almost 50 h at pH 5.0 and 7.4. Moreover, the encapsulation efficiency of the nanocarrier ranged from 70% to 92% and its RSV loading capacity from 9% to 14%, when [RSV] was between 100 and 200 mu M. The partition coefficient (K-p) of RSV between lipid and aqueous phase was log K-p = 3.37 +/- 0.10, suggesting moderate to high lipophilicity of this natural compound and reinforcing the lipid nanocarriers' suitability for RSV incorporation. The thermodynamic parameters of RSV partitioning in the lipid nanocarriers at 37 degrees C (Delta H = 43.76 +/- 5.68 kJ mol(-1); Delta S = 0.20 +/- 0.005 kJ mol(-1); and Delta G = -18.46 +/- 3.48 kJ mol(-1)) reflected the spontaneity of the process and the establishment of hydrophobic interactions. The cellular uptake mechanism of the RSV-loaded nanocarriers labeled with the lipophilic fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH) was studied in the eukaryotic model system Saccharomyces cerevisiae. Thirty minutes after incubation, yeast cells readily internalized nanocarriers and the spots of blue fluorescence of DPH clustered around the central vacuole in lipid droplets colocalized with the green fluorescence of the lipophilic endocytosis probe FM1-43. Subsequent studies with the endocytosis defective yeast deletion mutant (end3 Delta) and with the endocytosis inhibitor methyl-beta-cyclodextrin supported the involvement of an endocytic pathway. This novel nanotechnology approach opens good perspectives for medical applications.
引用
收藏
页码:1240 / 1249
页数:10
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