Background: The search for natural anticancer agents is a worthy scientific research goal, driven by 
the hope to lessen cancer's tremendous global burden. 
Objective: This study aimed at evaluating the cytotoxic activity of Gardenia latifolia Ait. (Rubiaceae) 
against lung (A549) and colon (HCT116) cancer cell lines. Cytotoxicity-guided isolation of the 
bioactive phytochemicals was conducted, followed by various mechanistic validations of the appealing 
cytotoxic metabolites. 
Methods: The cytotoxic effects were determined using MTT assay. The two most cytotoxic compounds 
were further evaluated for their effects on cell cycle progression and apoptotic capabilities using flow 
cytometry approach. Additionally, we conducted a molecular docking analysis to reveal their potential 
interactions with the human topoisomerase IIα. 
Results: The phytochemical investigation led to isolation of nine compounds including a new one, (-) 
1-acetyl 4,5-di-O-caffeoyl quinic acid. The latter compound was the most cytotoxic against the colon 
cancer cell line (IC50 1.9 µg/ml) with a remarkable tumor-selectivity (SI ≈ 15). Moreover, the isolated 
glycoside, 1-O-[6-O-(5-O-vanilloyl-β-ᴅ-apiofuranosyl)-β-ᴅ-glucopyranosyl]-3,4,5-trimethoxybenzene, 
showed selective cytotoxicity towards A549 and HCT116 cells (IC50 values of 3.8 and 3.3 µg/ml, 
respectively). Both compounds considerably affected the cell cycle distribution. They caused G2/M cell 
cycle arrest, showed apoptotic capabilities, and displayed significant in silico topoisomerase IIα 
inhibition.
Conclusion: Two cytotoxic and apoptotic compounds were reported from Gardenia latifolia. 
Subsequent in vivo studies and clinical trials should be conducted to substantiate their anticipated 
therapeutic values.

Promising cytotoxic effects of several Gardenia species (Rubiaceae) have been established 
by many studies. The current study evaluated MTT-based cytotoxic activities of the crude 
extract from Gardenia thunbergia L. f. aerial parts and four fractions thereof, including n-hexane, dichloromethane (DCM), ethyl acetate, and aqueous, against human leukemia (HL-60) 
and hepatoma (HepG2) cell lines, as well as the normal (WI38) cell line. Both non-polar 
fractions, n-hexane and dichloromethane, showed tumor-selective toxicities against both tested 
cancerous cell lines. These results sparked our interest in chemically characterising these 
bioactive fractions to reveal their cytotoxic components. The composition of n-hexane-soluble 
fraction was investigated via GC-MS analysis, while column chromatographic separation was 
used to isolate the components of DCM-soluble fraction. These isolated phytochemicals were 
identified via spectroscopic analyses. Besides, the chemotaxonomic value of the detected 
phytochemicals and their reported cytotoxic profiles were discussed

Thymoquinone (TQ), a pleiotropic compound isolated from the seeds of Nigella sativa has a great potential as a chemotherapeutic agent against several cancers. However, its limited aqueous solubility and poor stability impede its clinical utility. To overcome these hurdles, TQ was encapsulated into spanlastics made using Span 60 and various edge activators. The spanlastics were evaluated for particle size, polydispersity index, zeta potential, drug entrapment efficiency and in vitro drug release. TQ anticancer efficacy was tested in vitro against breast cancer cell line MCF-7. TQ-loaded spanlastics had spherical shape, particle size in the range of 92–285 nm and negative zeta potential (around −12 to −25 mV). The particle size and zeta potential were greatly influenced by the type and concentration of used edge activator. Tween 80 spanlastics had the smallest particle size (around 90–110 nm). High drug entrapment efficiency was observed for all the tested edge activators (around 76–99 %) and it was possible to modulate it by varying the edge activator and drug concentrations. Drug release rate was also dependent on the type and concentration of the edge activator. Tween 80 spanlastics, used as an optimum formulation resulted in 11.5- and 5-fold increase in TQ cytotoxic efficacy against MCF-7 cells compared with the free drug and the drug loaded into conventional niosomes, respectively. These results confirm that Tween 80 spanlastics could be a promising nano-delivery system to enhance the anticancer efficacy of TQ or similar anticancer drugs.

vesicles have shown tremendous potential to overcome these hurdles and improve the local therapeutic effect of these drugs.

Objective: This review article is aimed to shed light on flexible nano-vesicular carriers as a means to combat skin diseases.

Methods: The literature was reviewed using PubMed database using various keywords such as liposomes, flexible (deformable liposomes) (transferosomes), ethosomes, transethosomes, niosomes, and spanlastics.

Results: Liposomes and niosomes were found effective for the loading and release of both hydrophilic and lipophilic drugs. However, their limited skin penetration led to drug delivery to the outermost layers of skin only. This necessitates the search for innovative vesicular carriers, including liposomes, flexible (deformable liposomes), ethosomes, transethosomes, and spanlastics. These flexible nano-vesicular carriers showed enhanced drug delivery and deposition across various skin layers, which was better than their corresponding conventional vesicles. This resulted in superior drug efficacy against various skin diseases such as skin cancer, inflammatory skin diseases, superficial fungal infections, etc.

Conclusion: Flexible nano-vesicular carriers have proven themselves as efficient drug delivery systems that are able to deliver their cargo into the deep skin layers and thus, improve the therapeutic outcome of various skin diseases. However, there remain some challenges that need to be addressed before these nanocarriers can be translated from the lab to clinics.

This study aimed to encapsulate voriconazole into nano-micelles of poly(ethylene glycol)- block-poly(ε-caprolactone) to enhance its antifungal activity and reduce the required doses. The nanomicelles were prepared at various drug/polymer ratios, and their various physicochemical properties were studied. The nano-micelles had a small particle size in the range of ~50-60 nm and homogenous size distribution. The nano-micelles had high encapsulation efficiency and loading capacity in the range of ~40-95% and ~20-27%, respectively. Both encapsulation efficiency and loading capacity could be modulated by changing the drug/polymer ratio. Voriconazole release from the nano-micelles was much slower than the drug solution. The drug release pattern was biphasic, with a relatively faster initial phase followed by a sustained release. The antifungal efficacy was evaluated in vitro against Aspergillus flavus and Candida albicans using the drug solution in dimethyl sulfoxide/water as a control. The inhibition zone diameters of the fungi increased with increasing the drug concentration. The diameter of the inhibition zones against Aspergillus flavus was comparable for the nano-micelles and control. In contrast, the nano-micelles had significantly wider inhibition zones against Candida albicans than the control. These results show that poly(ethylene glycol)-block-poly(ε-caprolactone) nano-micelles could be used as a promising delivery system to enhance voriconazole antifungal efficacy.

The aim of this study was to prepare triamcinolone acetonide (TA)-loaded poly(ethylene glycol)-blockpoly(e-caprolactone) (PEG-b-PCL) and poly(ethylene glycol)-block-poly(lactic acid) (PEG-b-PLA) micelles as a potential treatment of ocular inflammation. The micelles were evaluated for particle size, drug loading capacity and drug release kinetics. Selected micellar formulations were dispersed into chitosan hydrogel and their anti-inflammatory properties were tested in rabbits using a carrageenan-induced ocular inflammatory model. Particle size ranged from 59.44 ± 0.15 to 64.26 ± 0.55 nm for PEG-b-PCL and from 136.10 ± 1.57 to 176.80 ± 2.25 nm for PEG-b-PLA micelles, respectively. The drug loading capacity was in the range of 6–12% and 15–25% for PEG-b-PCL and PEG-b-PLA micelles, respectively and was dependent on the drug/polymer weight ratio. TA aqueous solubility was increased by 5- and 10-fold after loading into PEG-b-PCL and PEG-b-PLA micelles at a polymer concentration as low as 0.5 mg/mL, respectively. PEG-b-PLA micelles suspended in chitosan hydrogel were able to sustain the drug release where only 42.8 ± 1.6% drug was released in one week. TA/PEG-b-PLA micelles suspended in chitosan hydrogel had better anti-inflammatory effects compared with the plain drug hydrogel or the drug micellar solution. Complete disappearance of the corneal inflammatory changes was observed for the micellar hydrogel. These results confirm the potential of PEG-b-PLA micelles suspended in chitosan hydrogel to enhance the anti-inflammatory properties of triamcinolone acetonide.