“…The solubility of LUT-HES NCs was 7.49 times the value of LUT ( P <0.001), contributed most by nano-size of LUT-HES NCs, which could be explained by the Ostwald–Freundlich equation. 14 , 39 Figure 5 The saturation solubility of different formulations (LUT, physical mixture and LUT-HES NCs) in water. …”
Section: Resultsmentioning
confidence: 99%
“…The solubility of LUT-HES NCs was 7.49 times the value of LUT (P<0.001), contributed most by nanosize of LUT-HES NCs, which could be explained by the Ostwald-Freundlich equation. 14,39 The in vitro dissolution of LUT powder and freeze-dried LUT-HES NCs powder was organized in simulated gastric and intestinal fluids. The in vitro dissolution curves are shown in Figure 6.…”
Section: Saturation Solubility and In Vitro Dissolution Studiesmentioning
Introduction
Although flavonoid compounds exhibit various pharmacological activities, their clinical applications are restricted by low oral bioavailability owing to their poor solubility. Nanocrystals (NCs) represent an excellent strategy for enhancing the oral bioavailability of flavonoids. Hydroxyethyl starch (HES), a biomaterial compound used as a plasma expander, could be an ideal stabilizer material for preparing flavonoid NCs.
Methods
HES was used to stabilize flavonoid nanocrystals (NCs), using luteolin (LUT) as a model drug. After full characterization, the freeze-drying and storage stability, solubility, intestinal absorption, pharmacokinetics, and in vivo anti-hyperuricemic effect of the optimized HES-stabilized LUT NCs (LUT-HES NCs) were investigated.
Results
Uniformed LUT-HES NCs were prepared with mean particle size of 191.1±16.8 nm, zeta potential of about −23 mV, drug encapsulation efficiency of 98.52 ± 1.01%, and drug loading of 49.26 ± 0.50%. The freeze-dried LUT-HES NCs powder showed good re-dispersibility and storage stability for 9 months. Notably, compared with the coarse drug, LUT-HES NCs exhibited improved saturation solubility (7.49 times), increased drug dissolution rate, enhanced Caco-2 cellular uptake (2.78 times) and oral bioavailability (Fr=355.7%). Pharmacodynamic studies showed that LUT-HES NCs remarkably lowered serum uric acid levels by 69.93% and ameliorated renal damage in hyperuricemic mice.
Conclusion
HES is a potential stabilizer for poorly soluble flavonoid NCs and provides a promising strategy for the clinical application of these compounds. LUT-HES NCs may be an alternative or complementary strategy for hyperuricemia treatment.
“…The solubility of LUT-HES NCs was 7.49 times the value of LUT ( P <0.001), contributed most by nano-size of LUT-HES NCs, which could be explained by the Ostwald–Freundlich equation. 14 , 39 Figure 5 The saturation solubility of different formulations (LUT, physical mixture and LUT-HES NCs) in water. …”
Section: Resultsmentioning
confidence: 99%
“…The solubility of LUT-HES NCs was 7.49 times the value of LUT (P<0.001), contributed most by nanosize of LUT-HES NCs, which could be explained by the Ostwald-Freundlich equation. 14,39 The in vitro dissolution of LUT powder and freeze-dried LUT-HES NCs powder was organized in simulated gastric and intestinal fluids. The in vitro dissolution curves are shown in Figure 6.…”
Section: Saturation Solubility and In Vitro Dissolution Studiesmentioning
Introduction
Although flavonoid compounds exhibit various pharmacological activities, their clinical applications are restricted by low oral bioavailability owing to their poor solubility. Nanocrystals (NCs) represent an excellent strategy for enhancing the oral bioavailability of flavonoids. Hydroxyethyl starch (HES), a biomaterial compound used as a plasma expander, could be an ideal stabilizer material for preparing flavonoid NCs.
Methods
HES was used to stabilize flavonoid nanocrystals (NCs), using luteolin (LUT) as a model drug. After full characterization, the freeze-drying and storage stability, solubility, intestinal absorption, pharmacokinetics, and in vivo anti-hyperuricemic effect of the optimized HES-stabilized LUT NCs (LUT-HES NCs) were investigated.
Results
Uniformed LUT-HES NCs were prepared with mean particle size of 191.1±16.8 nm, zeta potential of about −23 mV, drug encapsulation efficiency of 98.52 ± 1.01%, and drug loading of 49.26 ± 0.50%. The freeze-dried LUT-HES NCs powder showed good re-dispersibility and storage stability for 9 months. Notably, compared with the coarse drug, LUT-HES NCs exhibited improved saturation solubility (7.49 times), increased drug dissolution rate, enhanced Caco-2 cellular uptake (2.78 times) and oral bioavailability (Fr=355.7%). Pharmacodynamic studies showed that LUT-HES NCs remarkably lowered serum uric acid levels by 69.93% and ameliorated renal damage in hyperuricemic mice.
Conclusion
HES is a potential stabilizer for poorly soluble flavonoid NCs and provides a promising strategy for the clinical application of these compounds. LUT-HES NCs may be an alternative or complementary strategy for hyperuricemia treatment.
“…On the other hand, the relative intensity of the diffraction peaks of nanosuspensions decreased or disappeared compared with KAE, indicating that the crystallinity was reduced after the preparation of nanosuspensions, which had more amorphous structure than KAE. Moreover, this phenomenon might be related to the process of highpressure homogenization, leading to the transformation of the crystal structure, which might increase the solubility and bioavailability of KAE subsequently [41]. The DSC result of KAE, TPGS, physical mixture, and freeze-dried TPGS-KAE-NSps were displayed in Fig.…”
“…However, the agglomeration of nanoparticles occurred during the lyophilization, which made it di cult for them to return to the initial state after re-dispersing in water. It was necessary that cryoprotectants should be added to prevent the clustering of drug nanoparticles and keep the original structure of the nanosuspensions [41]. In this study, the TPGS-KAE-NSps lyophilized powders were prepared with different concentration cryoprotectants, the particle size of which was measured to screen out the optimal lyophilized prescription, and the results were presented in Fig.…”
Section: Lyophilization Process Of Tpgs-kae-nspsmentioning
Kaempferol (KAE) is a natural avonoid compound with antitumor activity. However, the low aqueous solubility, poor chemical stability and suboptimal bioavailability greatly restricted its clinical application of cancer. In order to overcome these shortages and enhance the antitumor effect of KAE, we developed a kaempferol nanosuspensions (KAE-NSps) with D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) as stabilizer, screened the optimal preparation process, and investigated the basic properties and the antitumor effect in the study. The results demonstrated that the particle size was 186.6 ± 2.6 nm of the TPGS-KAE-NSps optimized, the shape of which was fusiform under the transmission electron microscope. The 2% (w/v) glucose was used as the cryoprotectant for TPGS-KAE-NSps, whose drug loading content was 70.31 ± 2.11%, and the solubility was improved prominently compared to KAE. The stability and biocompatibility of TPGS-KAE-NSps were favorable, which had a certain sustained release effect. Moreover, TPGS-KAE-NSps clearly seen to be taken in the cytoplasm exhibited a stronger cytotoxicity and suppression of cell migration, higher apoptosis rate and more intracellular ROS production compared to KAE in vitro cell experiments. In addition, TPGS-KAE-NSps showed a stronger inhibition of tumor growth (the tumor inhibition rate of high dose intravenous injection group was 68.9 ± 1.46%) than KAE with no obvious toxicity on 4T1 tumor-bearing mice. Overall, TPGS-KAE-NSps prepared improved the defect and the antitumor effect of KAE notably, which was a promising nanodrug delivery system for KAE and was expected to become a clinical antitumor drug.
“…Li et al prepared quercetin nanosuspensions that exhibited drug release of 68.73%, improved stability, and bioavailability of quercetin[59]. Quercetin nanosuspensions were prepared using high-shearing, HPH techniques, and the developed quercetin nanosuspensions showed enhanced stability and antioxidant activity[60].…”
Quercetin is a natural bioflavonoid and is an inevitable part of a person’s daily diet. It exhibits anti-inflammatory, anti-oxidant, anti-cancer, anti-microbial effects and is used for the treatment of several diseases like cancer, cardiovascular ailments, and microbial infections. The major limitations of quercetin are low water solubility, less chemical stability, low bioavailability, and short biological half-life. All these major drawbacks can be overcome by its encapsulation in various nanocarriers (nanoparticles, nanoliposomes, nanocrystals, nanomicelles, etc). Such quercetin encapsulated nanoformulations displayed enhanced solubility, stability, bioavailability, high encapsulation efficiency, controlled drug release and extended systemic circulation time period. Quercetin loaded nanocarriers can easily pass across different barriers like blood brain barrier (BBB), skin barriers, mucosal membrane, hence providing target site specific delivery. They also exhibited improved therapeutic effects such as enhanced anti-cancer, anti-diabetic, anti-microbial, anti-inflammatory, anti-psoriasis, anti-oxidant, anti-asthmatic, anti-acne, skin-whitening, hepatoprotective, photoprotective, neuroprotective, nephroprotective and cardioprotective actions. Major health issues associated with nanoformulations are risk of cytotoxicity, oxidative stress, DNA damage, and mutations that can be minimised with continual advancements in nanotechniques. The present review discusses quercetin, its historical background, pharmacokinetics, mechanism of action, and therapeutic applications with major emphasis on the quercetin nanoformulations such as nanoparticles, nanoemulsions, nanoliposomes, nanocrystals, nanosuspensions and nanomicelles that enhances its physicochemical stability, solubility, and therapeutic applications. Also this review includes different quercetin nanoformulations developed for colon cancer and colorectal cancer treatment, brief description of pre-clinical & clinical studies, toxicological concerns, challenges & opportunities, future aspects, patents and marketed quercetin products.
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