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Hyaluronic acid (HA) is a glycosaminoglycan that was first isolated and identified from the vitreous body of a bull's eye. HA is ubiquitous in the soft connective tissues of animals and therefore has high tissue compatibility for use in medication. Because of HA's biological safety and water retention properties, it has many ophthalmology-related applications, such as in intravitreal injection, dry eye treatment, and contact lenses. Due to its broad range of applications, the identification and quantification of HA is a critical topic. This review article discusses current methods for analyzing HA. Contact lenses have become a widely used medical device, with HA commonly used as an additive to their production material, surface coating, and multipurpose solution. HA molecules on contact lenses retain moisture and increase the wearer's comfort. HA absorbed by contact lenses can also gradually release to the anterior segment of the eyes to treat dry eye. This review discusses applications of HA in ophthalmology. [ABSTRACT FROM AUTHOR]

Liver cancer is listed as the fifth-ranked cancer, responsible for 9.1% of all cancer deaths globally due to its assertive nature and poor survival rate. To overcome this obstacle, efforts have been made to ensure effective cancer therapy via nanotechnology utilization. Recent studies have shown that functionalized graphene oxide (GO)-loaded protocatechuic acid has shown some anticancer activities in both passive and active targeting. The nanocomposites' physicochemical characterizations were conducted. A lactate dehydrogenase experiment was conducted to estimate the severity of cell damage. Subsequently, a clonogenic assay was carried out to examine the colony-forming ability during long-term exposure of the nanocomposites. The Annexin V/ propidium iodide analysis showed that nanocomposites induced late apoptosis in HepG2 cells. Following the intervention of nanocomposites, cell cycle arrest was ascertained at G2/M phase. There was depolarization of mitochondrial membrane potential and an upregulation of reactive oxygen species when HepG2 cells were induced by nanocomposites. Finally, the proteomic profiling array and quantitative reverse transcription polymerase chain reaction revealed the expression of pro-apoptotic and anti-apoptotic proteins induced by graphene oxide conjugated PEG loaded with protocatechuic acid drug folic acid coated nanocomposite (GOP–PCA–FA) in HepG2 cells. In conclusion, GOP–PCA–FA nanocomposites treated HepG2 cells exhibited significant anticancer activities with less toxicity compared to pristine protocatechuic acid and GOP–PCA nanocomposites, due to the utilization of a folic acid-targeting nanodrug delivery system. [ABSTRACT FROM AUTHOR]

Gemcitabine (dFdC or Gem) is a water-soluble cytotoxic drug, with poor cellular uptake in the absence of a nucleoside transporter. To improve its diffusion through membranes, it was modified by grafting of a squalenoyl moiety. In water, this derivative is able to form stable and monodispersed nanoparticles made of inverse hexagonal phases. The formation and interfacial properties of the squalenoyl gemcitabine (SQ-Gem) nanoparticles, and their ability to interact with phospholipid and cholesterol monolayers modeling a biomembrane, was assessed from surface tension measurements and Brewster angle microscopy. To get a better insight into the mechanisms of SQ-Gem interaction with the various lipids, the interfacial behavior of SQ-Gem and squalene was also studied by surface pressure and surface potential measurements, in the absence and in the presence of phospholipids and cholesterol. The results showed that SQ-Gem nanoparticles adsorbed at the free air/water interface and disrupted to form a monolayer. SQ-Gem molecules released from the adsorbed nanoparticles were also able to penetrate into condensed phospholipid-cholesterol mixed monolayers. The kinetics of this penetration was apparently controlled by intermolecular interactions between the drug and the adsorbed lipids. Whereas distearoylphosphatidylcholine (DSPC) hindered SQ-Gem penetration, cholesterol favored it, which could have important implications in the therapeutic field since cholesterol targeting could alter lipid raft composition and cancer cell survival., (© 2011 American Chemical Society)

Using the anticancer compound paclitaxel as a model drug, this study investigates the potential of the squalenoylation technology (i.e., bioconjugation with the natural lipid squalene) in addressing the drug ability and delivery issues of poorly soluble therapeutic agents. In this view, a variety of novel squalene-based prodrugs of the anticancer compound paclitaxel were synthesized, which produced nanoparticles in water. These prodrugs were obtained by covalent coupling of the paclitaxel 2'-hydroxyl group as direct ester, as well as with a succinate or a diglycolate ester as cleavable linker to the 1,1',2-tris-norsqualenoic acid. The hydrophilicity of these paclitaxel bioconjugates was increased by placing poly(ethylene glycol) chains of different lengths between paclitaxel and the squalenoyl moiety. All these prodrugs self-assembled into nanosized aggregates in aqueous solution as characterized by dynamic light scattering, atomic force microscopy, and transmission electron microscopy. The critical aggregation concentration was very low, ranging from 0.09 to 0.4 mg/L. Zeta potential measurements revealed that all squalenoyl-paclitaxel nanoassemblies (NA) held a global negative charge and appeared stable in water for several weeks as determined by particle size measurement. The release of paclitaxel from NA was evaluated in different conditions and in the presence of serum and depended on the nature of the linker used. Preliminary biological assessment showed that these squalenoyl-paclitaxel NA induced the formation of microtubule bundles in HT-29 and KB-31 cells, and additionally displayed notable cytotoxicity on a lung tumor cell line. Furthermore, the cytotoxic activity of these different prodrugs correlated closely with the observed linker stability. Overall, the squalenoylation nanotechnology opens up interesting perspectives for the development of injectable prodrugs of poorly soluble therapeutic compounds by addressing the associated physicochemical and biopharmaceutical challenges.

The study developed cytotoxic macromolecular conjugates that specifically target the folate receptor and deliver the drug into cell cytoplasm. The anticancer agent paclitaxel was conjugated to human serum albumin (HSA) and this drug-albumin conjugate was further equipped with folic acid, linked via an extended poly(ethylene glycol) spacer. Preparation was carried out in a heterogeneous phase system exploiting the binding ability of Cibacron Blue dye to HSA. Unreacted reagents were easily removed and, after purification by gel filtration, the conjugate was fully characterized. Binding and in vitro cytotoxicity studies on human nasopharyngeal epidermal carcinoma KB and colorectal carcinoma HT-29 cells (as negative control) demonstrated increased selectivity and anti-tumoral activity.

The aim of this study was to develop both a physical and a chemical protection of the anticancer drug gemcitabine, which suffers from a rapid plasmatic metabolization. For this purpose, we used a series of lipophilic derivatives of gemcitabine in which an acyl chain is covalently coupled to the 4-amino group of gemcitabine; moreover, a physical protection of the drug was attempted by incorporating these lipophilic derivatives into poly(H(2)NPEGCA-co-HDCA) nanospheres and nanocapsules. Nanoparticles were prepared by nanoprecipitation of the poly(H(2)NPEGCA-co-HDCA) copolymer and their size, zeta potential and encapsulation efficiency were further characterized. These results have been relied on lipophilicity and flexibility studies. Data showed that only the more lipophilic derivative, 4-(N)-stearoylgemcitabine, was incorporated with a high yield. Thus, 4-(N)-stearoylgemcitabine-containing nanospheres and nanocapsules were further analyzed by differential scanning calorimetry. Their cytotoxicity was tested on two human cancer cell lines and compared to that of gemcitabine and free 4-(N)-stearoylgemcitabine.

Objective: To investigate a possible pharmacokinetic interaction between gemcitabine (GEM) and vinorelbine (VNR), when co-administered following the alternate sequences GEM-VNR and VNR-GEM., Methods: Enrolled in this study were 31 patients with different advanced carcinoma: 9 patients were given GEM (1 h i.v. infusion, 1000 mg/m2) followed after 5 min by VNR (10 min i.v. infusion, 25 mg/m2) (GEM-VNR sequence); 17 patients received VNR followed by GEM (VNR-GEM sequence), at the same doses and with the same infusion period; as a control group (GEM), 5 patients were given only single-agent gemcitabine (1 h i.v. infusion, 1000 mg/m2)., Results: GEM serum levels showed higher Cmax and AUC(tot) in the VNR-GEM protocol than in the GEM-VNR and GEM groups. The GEM pharmacokinetic profile in both schedules showed biphasic elimination, as in monotherapy. VNR concentration/time curves showed rapid plasma clearance and wide interpatient variability in both sequences. VNR Cmax was higher in the VNR-GEM group than in GEM-VNR, while VNR AUC(tot) and Cl(tot) did not differ significantly in the two sequences., Conclusions: Some pk-values were altered for both GEM and VNR, following the two alternate protocols. A possible rationale for this behaviour is that VNR and GEM may influence each other during liver elimination extraction and metabolism.

The taxanes, paclitaxel and docetaxel, are anticancer agents used in clinical trials against ovarian carcinoma, breast, lung and head/neck cancer. Paclitaxel, very insoluble in water, is generally formulated using Cremophor EL. Docetaxel, more soluble in water, is formulated using Tween 80 and ethanol. Tween 80, albeit less toxic than Cremophor EL, may be responsible of some toxic effects. To eliminate these vehicles and improve the drug's antitumor efficacy, taxanes have been incorporated in liposomes. We compared formulation, stability, biodistribution and pharmacokinetics of docetaxel in conventional and PEGylated liposomes. Of the several formulations examined, docetaxel-liposomes composed of ePC/PG/CHOL 9:1:2 and ePC/PG/DSPE-PEG2000/CHOL 9:1:2:0.7 were the most effective. Both conventional and PEGylated docetaxel-liposomes were stable at 4 degrees C after 15 days, whereas in the presence of serum at 37 degrees C they were less stable. The IC50 values of docetaxel-liposomes, evaluated on HT-29 and Igrov1 cell lines, remained very high. Pharmacokinetics and biodistribution were evaluated in Balb/c mice after i.v. injection of [14C]docetaxel, formulated in Tween 80 or in 3H-labeled conventional or PEGylated liposomes. The t(1/2)beta, which was low for docetaxel (52.3 min), rose to 260 min for conventional docetaxel-liposomes and to 665 min for PEGylated docetaxel liposomes. Biodistribution studies confirmed the pharmacokinetics.