be effective for oral and topical delivery of resveratrol. Polymeric lipid-core
nanocapsules have been loaded with trans-resveratrol to improve its biodistribution
and decrease its very fast metabolism. Nanocapsules (size, 240 nm) of trans-resveratrol were prepared and their in vivo biodistribution in rats evaluated, showing
improved gastro-intestinal safety [165]. In order to enhance the oral bioavailability,
trans-resveratrol NPs were prepared by temperature-controlled antisolvent precipitation with hydroxypropyl methyl cellulose as the stabilizer. The mean particle size
was well controlled, ranging between 232 and 560 nm by adjusting the precipitation
temperature and was decreased by lowing the precipitation temperature during the
antisolvent process. The study concluded that that the temperature-controlled
antisolvent precipitation technique can be considered promising for obtaining
nanosized particles to enhance the saturation solubility and dissolution rate, and
could be an effective method for achieving therapeutic effects for poorly watersoluble food ingredients and nutraceuticals [166].
The capability of resveratrol to elicit many cellular responses, including cell
cycle arrest, differentiation, and apoptosis makes it a potential anticancer agent.
Resveratrol is incorporated into methoxyPEG-PCL-based nanoparticles with high
encapsulation efficiency and its in vitro cytotoxic effect was analyzed in glioma
cells (C6). Intracellular ROS levels were shown to exploit the possible antiglioma
mechanisms of resveratrol-loaded NPs. Resveratrol NPs demonstrated better efficacy against glioma cells due to the superior cell membrane penetrating ability
of the NPs and the ROS scavenging potential of released resveratrol [167]. Wang
et al. proposed a strategy of targeting cancer cell mitochondria by resveratrol
liposomes [169]. They synthesized a targeting material, dequlinium–poly(ethylene
glycol)–distearoylphosphatidylethanolamine (DQA–PEG2000–DSPE), which was
used as mitochondriotropic molecule for modifying the surface of liposomes, and
evaluated its apoptotic potential in resistant lung cancer cells. Mitochondrialtargeting resveratrol liposomes (size 70–80 nm) exhibited a strong inhibitory effect
on the proliferation of A549 cells. Subcellular localization of the drug in A549 and
A59/cDDP cells using confocal laser microscopy clearly showed the mitochondrial
targeting of the NPs. The inhibitory effect of mitochondrial-targeting resveratrol
liposomes on resistant lung cancer xenografts was studied and superior antitumor
effects by inducing apoptosis via the mitochondria signaling pathway were
achieved with the NPs compared with free resveratrol. The study proved that
mitochondrial-targeting resveratrol liposomes modified with the targeting
DQA–PEG2000–DSPE conjugate could provide a potential strategy for treating
the intrinsic resistant lung cancers [168].
The potential of transferosomes and ethanol-containing vesicles were evaluated
for their delivery of resveratrol through skin. Transferosomes (size 83 nm)
encapsulating trans-resveratrol were prepared with surfactant polysorbate 80
(Tw80), sodium cholate (SC), and sodium deossicholate (SDC) and 116-nm
ethanol-containing vesicles of different lipid composition, namely soy phosphatidylcholine (SPC) and cholesterol. Cytotoxicity and the inhibition of ROS production
and lipid peroxidation were evaluated on H 2 O 2 -stimulated human keratinocytes
(HaCaT). The presence of trans-resveratrol can have a protective effect, reducing
Phytomedicine-Loaded Polymeric Nanomedicines: Potential Cancer Therapeutics
229
nanocapsules have been loaded with trans-resveratrol to improve its biodistribution
and decrease its very fast metabolism. Nanocapsules (size, 240 nm) of trans-resveratrol were prepared and their in vivo biodistribution in rats evaluated, showing
improved gastro-intestinal safety [165]. In order to enhance the oral bioavailability,
trans-resveratrol NPs were prepared by temperature-controlled antisolvent precipitation with hydroxypropyl methyl cellulose as the stabilizer. The mean particle size
was well controlled, ranging between 232 and 560 nm by adjusting the precipitation
temperature and was decreased by lowing the precipitation temperature during the
antisolvent process. The study concluded that that the temperature-controlled
antisolvent precipitation technique can be considered promising for obtaining
nanosized particles to enhance the saturation solubility and dissolution rate, and
could be an effective method for achieving therapeutic effects for poorly watersoluble food ingredients and nutraceuticals [166].
The capability of resveratrol to elicit many cellular responses, including cell
cycle arrest, differentiation, and apoptosis makes it a potential anticancer agent.
Resveratrol is incorporated into methoxyPEG-PCL-based nanoparticles with high
encapsulation efficiency and its in vitro cytotoxic effect was analyzed in glioma
cells (C6). Intracellular ROS levels were shown to exploit the possible antiglioma
mechanisms of resveratrol-loaded NPs. Resveratrol NPs demonstrated better efficacy against glioma cells due to the superior cell membrane penetrating ability
of the NPs and the ROS scavenging potential of released resveratrol [167]. Wang
et al. proposed a strategy of targeting cancer cell mitochondria by resveratrol
liposomes [169]. They synthesized a targeting material, dequlinium–poly(ethylene
glycol)–distearoylphosphatidylethanolamine (DQA–PEG2000–DSPE), which was
used as mitochondriotropic molecule for modifying the surface of liposomes, and
evaluated its apoptotic potential in resistant lung cancer cells. Mitochondrialtargeting resveratrol liposomes (size 70–80 nm) exhibited a strong inhibitory effect
on the proliferation of A549 cells. Subcellular localization of the drug in A549 and
A59/cDDP cells using confocal laser microscopy clearly showed the mitochondrial
targeting of the NPs. The inhibitory effect of mitochondrial-targeting resveratrol
liposomes on resistant lung cancer xenografts was studied and superior antitumor
effects by inducing apoptosis via the mitochondria signaling pathway were
achieved with the NPs compared with free resveratrol. The study proved that
mitochondrial-targeting resveratrol liposomes modified with the targeting
DQA–PEG2000–DSPE conjugate could provide a potential strategy for treating
the intrinsic resistant lung cancers [168].
The potential of transferosomes and ethanol-containing vesicles were evaluated
for their delivery of resveratrol through skin. Transferosomes (size 83 nm)
encapsulating trans-resveratrol were prepared with surfactant polysorbate 80
(Tw80), sodium cholate (SC), and sodium deossicholate (SDC) and 116-nm
ethanol-containing vesicles of different lipid composition, namely soy phosphatidylcholine (SPC) and cholesterol. Cytotoxicity and the inhibition of ROS production
and lipid peroxidation were evaluated on H 2 O 2 -stimulated human keratinocytes
(HaCaT). The presence of trans-resveratrol can have a protective effect, reducing
Phytomedicine-Loaded Polymeric Nanomedicines: Potential Cancer Therapeutics
229