Delivery of synergistic polyphenol combinations using biopolymer-based systems: Advances in physicochemical properties, stability and bioavailability.

When consumed at sufficiently high levels, polyphenols may provide health benefits, which is linked to their antidiabetic, antiinflamatory, antimicrobial, antioxidant, antitumor, and hypolipidemic properties. Moreover, certain polyphenol combinations exhibit synergistic effects when delivered together - the combined polyphenols have a higher biological activity than the sum of the individual ones. However, the commercial application of polyphenols as nutraceuticals is currently limited because of their poor solubility characteristics; instability when exposed to light, heat, and alkaline conditions; and, low and inconsistent oral bioavailability. Colloidal delivery systems are being developed to overcome these challenges. In this article, we review the design, fabrication, and utilization of food-grade biopolymer-based delivery systems for the encapsulation of one or more polyphenols. In particular, we focus on the creation of delivery systems constructed from edible proteins and polysaccharides. The optimization of biopolymer-based delivery systems may lead to the development of innovative polyphenol-enriched functional foods that can improve human health and wellbeing.

Enhanced functional properties of pea protein isolate microgel particles modified with sodium alginate: Mixtures and conjugates.

Protein microgels are emerging as versatile soft particles due to their desirable interfacial activities and functional properties. In this study, pea protein isolate microgel particles (PPIMP) were prepared by heat treatment and transglutaminase crosslinking, and PPIMP were non-covalently and covalently modified with sodium alginate (SA). The effects of polymer ratio and pH on the formation of PPIMP-SA mixtures and conjugates were investigated. The optimal ratio of PPIMP and SA was found to be 20:1, with the optimal pH being 7 and 10, respectively. PPIMP-SA conjugates were prepared by Maillard reaction. It was found that ultrasound (195 W, 40 min) enhanced the degree of glycation of PPIMP, with a highest value of 37.21 ± 0.71 %. SDS-PAGE, browning intensity and FTIR data also confirmed the formation of PPIMP-SA conjugates. Compared with PPIMP and PPIMP-SA mixtures, PPIMP-SA conjugates exhibited better thermal stability, antioxidant, emulsifying and foaming properties, which opens up opportunities for protein microgel in various food applications.

Advances in enhancing the mechanical properties of biopolymer hydrogels via multi-strategic approaches.

The limited mechanical properties of biopolymer-based hydrogels have hindered their widespread applications in biomedicine and tissue engineering. In recent years, researchers have shown significant interest in developing novel approaches to enhance the mechanical performance of hydrogels. This review focuses on key strategies for enhancing mechanical properties of hydrogels, including dual-crosslinking, double networks, and nanocomposite hydrogels, with a comprehensive analysis of their underlying mechanisms, benefits, and limitations. It also introduces the classic application scenarios of biopolymer-based hydrogels and the direction of future research efforts, including wound dressings and tissue engineering based on 3D bioprinting. This review is expected to deepen the understanding of the structure-mechanical performance-function relationship of hydrogels and guide the further study of their biomedical applications.

Double network hydrogels: Design, fabrication, and application in biomedicines and foods.

Research on the design, fabrication, and application of double network (DN) hydrogels, assembled from pairs of polymers, has grown recently due to their unique structural, physicochemical, and functional properties. DN hydrogels can be designed to exhibit a broader range of functional attributes than single network (SN) ones, which extends their applications in various fields. There has been strong interest in the development of biopolymer DN hydrogels because of their environmental, sustainability, and safety benefits. However, there is limited knowledge on the formation and application of these novel materials. This article reviews the principles underlying the design and fabrication of hydrogels using different crosslinking approaches, including covalent and/or non-covalent bonding, and the formation mechanisms, network structures, and functional attributes of different DN hydrogels. The impact of polymer composition, structural organization, and bonding on the mechanical and functional properties of DN hydrogels is reviewed. Potential applications of these hydrogels are highlighted, including in tissue engineering, biomedicines, and foods. The functional attributes of DN hydrogels can be tailored to each of these applications by careful selection of the biopolymers and crosslinking mechanisms used to assemble them. Finally, areas where further research are needed to overcome the current limitations of DN hydrogels are highlighted.

Co-delivery of curcumin and epigallocatechin gallate in W/O/W emulsions stabilized by protein fibril-cellulose complexes.

Hydrophobic curcumin and hydrophilic epigallocatechin gallate (EGCG) are reported to exhibit a variety of biological activities and may exhibit synergistic effects when used in combination. A co-encapsulation system was developed to improve their applicability and bioavailability. This delivery system consisted of a water-in-oil-in-water (W1/O/W2) double emulsion stabilized by whey protein isolate fibrils (WPIFs) and cellulose nanocrystals (CNCs). Double emulsions were fabricated using a two-step emulsification method using either WPIF-CNC complexes or WPIF alone. The physicochemical stability, encapsulation performance, and digestive properties of the delivery systems were then investigated. The double emulsions stabilized by the WPIF-CNC complexes were more resistant to heat and salt stress, exhibited greater encapsulation stability, and had a higher bioaccessibility for curcumin (67.8%) and EGCG (68.9%) than those stabilized by WPIFs. This research shows that the stability and bioaccessibility of curcumin and EGCG can be enhanced by co-encapsulating them in emulsion-based delivery systems using nanostructured protein-polysaccharide complexes.

Development of pH-responsive active film materials based on purple corncob and its application in meat freshness monitoring.

The use of petroleum-based food packaging materials is causing environmental damage and increasing greenhouse gas production. Consequently, there is a great interest in developing smart and sustainable alternative materials. In this study, an agricultural waste product (purple corncob extract, PCCE) was used as a raw material to prepare environmentally friendly pH-sensitive packaging materials. Natural pH-sensitive pigments (anthocyanins) and lignin-containing cellulose nanocrystals (LCNC) were extracted from the purple corncobs. A cationic biopolymer (chitosan) was used as a scaffolding material to assemble the film matrix. Composite film (LCNC-PCCE-chitosan) was produced using a simple solvent casting method. Fourier transform infrared spectroscopy and scanning electron microscopy analyses showed that the PCCE and LCNC were well dispersed within the chitosan matrix and they interacted with the matrix through hydrogen bonding and electrostatic interactions. The addition of LCNC improved the hydrophobicity and mechanical properties of the film and imparted antioxidant activity and UV-blocking properties. The presence of anthocyanins in the PCCE endowed the film with a sensitive and reversible pH response, which could be well used to monitor changes in the freshness of pork and shrimp products.

Enhancing emulsion stability and performance using dual-fibrous complexes: Whey protein fibrils and cellulose nanocrystals.

Edible proteins can self-assemble into fibrils, which can improve their performance as emulsifiers. However, they are limited in some food applications. We prepared whey protein isolate fibril-cellulose nanocrystal complexes (WPIF-CNC) by electrostatic complexation. The stabilities of emulsions prepared using either WPIF or WPIF-CNC were compared to evaluate the effect of complexation on emulsion formation and properties. Moreover, the potential of the emulsions to act as delivery systems for curcumin was investigated. WPIF and CNC were found to complex by hydrogen bonding, hydrophobic, and electrostatic interactions. The complexes formed were good Pickering stabilizers in oil-in-water emulsions. Emulsions formulated using the complexes were more resistant to creaming than those stabilized by WPIF. The complexes were able to form self-supporting gelled emulsions at 70 % oil concentration, which protected curcumin from photo- and thermal-degradation. Consequently, dual-fibrous complexes may have application in the food industry as novel emulsifiers for the creation of nutraceutical delivery systems.

Clinical implication of quantitative flow ratio to predict clinical events after drug-coated balloon angioplasty in patients with in-stent restenosis.

BACKGROUND: The association between the quantitative flow ratio (QFR) and adverse events after drug-coated balloon (DCB) angioplasty for in-stent restenosis (ISR) lesions has not been investigated. HYPOTHESIS: Post-procedural QFR is related to adverse events in patients undergoing DCB angioplasty for ISR lesions. METHODS: This retrospective study included data from patients undergoing DCB angioplasty for drug-eluting stent (DES) ISR between January 2016 and February 2019. The QFR was measured at baseline and after DCB angioplasty. The endpoint was the vessel-oriented composite endpoint (VOCE), defined as a composite of cardiac death, vessel-related myocardial infarction, and ischemia-driven target vessel revascularization. RESULTS: Overall, 177 patients with 185 DES-ISR lesions were included. During 1-year follow-up, 27 VOCEs occurred in 26 patients. The area under curve (AUC) of the post-procedural QFR was statistically greater than that of the in-stent percent diameter stenosis (0.77, 95% confidence interval [CI] 0.67-0.87 vs. 0.64, 95% CI 0.53-0.75; p = .032). Final QFR cutoff of 0.94 has the best predictive accuracy for VOCE. A QFR > 0.94 was associated with a lower risk of VOCE compared to a QFR ≤ 0.94 (log-rank test, p < .0001). Survival analysis using the multivariable Cox model showed that a post-procedural QFR ≤ 0.94 was an independent predictor of 1-year VOCE (hazard ratio 6.53, 95% CI 2.70-15.8, p < .001). CONCLUSIONS: A lower QFR value was associated with worse clinical outcomes at 1 year after DCB angioplasty for DES-ISR.

A randomized comparison of a novel iopromide-based paclitaxel-coated balloon Shenqi versus SeQuent Please for the treatment of in-stent restenosis.

BACKGROUND: Treatment of coronary in-stent restenosis (ISR) remains challenging in contemporary clinical applications. Drug-coated balloon (DCB) angioplasty offers an effective treatment for ISR. Shenqi is a novel iopromide-based paclitaxel-coated balloon and its clinical safety, effectiveness and angiographic efficacy in patients with ISR have not been investigated. METHODS: A total of 216 subjects with the first occurrence of ISR at 11 investigational sites in China were randomly allocated in a 1:1 fashion to treatment with DCB SeQuent Please or Shenqi. Clinical follow-up was planned at 1, 6, 9 and 12 months, and angiographic follow-up was planned at 9 months. The study was powered for the primary endpoint of 9-month in-segment late loss. RESULTS: At 9-month follow-up, the in-segment late loss was 0.29 ± 0.43 mm with Shenqi versus 0.30 ± 0.46 mm with SeQuent Please, and the one-sided 97.5% upper confidence limit of the difference was 0.14 mm, achieving noninferiority of Shenqi compared with SeQuent Please (P = 0.002). In total, 12 patients developed target lesion failure (TLF) in the Shenqi group compared with 16 patients in the SeQuent Please group (10.91% versus 15.09%; P = 0.42) within 1 year. TLF was mainly driven by target lesion revascularization (9.09%) followed by target vessel-related myocardial infarction (1.82%) and cardiovascular death (0.91%) in the Shenqi group. CONCLUSIONS: Shenqi DCB was noninferior to SeQuent Please DCB for the primary endpoint of 9-month in-segment late loss. Shenqi DCB may become an attractive alternative treatment for patients with coronary ISR, withholding the need for additional stent implantation.

Sesamol incorporated cellulose acetate-zein composite nanofiber membrane: An efficient strategy to accelerate diabetic wound healing.

Recently, the function of nanofiber membranes prepared from electrospinning in accelerating wound healing has attracted wide attention. In this study, novel nanofiber membranes consisted of cellulose acetate (CA) and zein were fabricated to provide efficient delivery vehicles for sesamol, and then the effect of sesamol-loaded composite nanofiber membranes on the wound healing of diabetic mice was studied. It was found the critical concentration of CA was between 15% and 25% (w/v), and the most suitable concentration of stabilizing fibers was 22.5%. When the CA/zein ratio was 12:8, the fiber obtained small diameter and uniform distribution, stable intermolecular structure, low infiltration speed and high stability in water. The composite nanofiber membrane with high-dose sesamol (5% of total polymer concentration, w/w) promoted formation of myofibroblasts by enhancing TGF-ß signaling pathway transduction, and promoted keratinocyte growth by inhibiting chronic inflammation in wounds, thus enhancing wound healing in diabetic mice. This study can further broaden the application range of sesamol, CA and zein, and provide reference for the design and development of new wound dressings in the future.

Delivery of Sesamol Using Polyethylene-Glycol-Functionalized Selenium Nanoparticles in Human Liver Cells in Culture.

Anticancer nanoparticles were fabricated by linking the nanoparticles of two known anticancer agents, sesamol and selenium, using polyethylene glycol (PEG). The successful fabrication of the sesamol-PEG-selenium nanoparticles (PEG-SeNPs), which had a sesamol loading efficiency of 10.0 ± 0.5 wt %, was demonstrated using different spectroscopic techniques. The impact of the nanoparticles on model cancer cells (HepG2) was established using the cell activity test, morphological observation, and fluorescent staining, which all showed that nanoparticles effectively inhibited the HepG2 cells. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays showed that the concentration of the sample that inhibits 50% of the cells of PEG-SeNPs and sesamol-PEG-SeNPs on HepG2 cells was 413.8 and 68.7 µg/mL, respectively, which indicated the synergistic inhibition between sesamol and selenium nanoparticles. Furthermore, flow cytometry showed that sesamol-PEG-SeNPs exhibited higher apoptosis than either sesamol or PEG-SeNPs alone. Finally, western blot confirmed that the apoptostic ability of sesamol-PEG-SeNPs was associated with downregulation of Bcl-2 and procaspase-3, upregulation of Bax and PARP, and discharge of cytochrome c into the cytosol. Our findings suggest the novel sesamol nanoparticles may be efficient anticancer agents.

Nonrandomized comparison of coronary stenting under intravascular ultrasound guidance of direct stenting without predilation versus conventional predilation with a semi-compliant balloon versus predilation with a new scoring balloon.

This study was conducted to determine the influence of lesion preparation using the AngioSculpt balloon on final stent expansion. Stent expansion remains an important predictor of restenosis and subacute thrombosis, even in the drug-eluting stent (DES) era. In these patients, the role of different predilation strategies has yet to be established. Two hundred ninety-nine consecutive de novo lesions treated with 1 >2.5-mm DES (Cypher or Taxus) under intravascular ultrasound guidance without postdilation, using 3 implantation strategies, were studied: (1) direct stenting without predilation (n = 145), (2) predilation with a conventional semi-compliant balloon (n = 117), and (3) predilation with the AngioSculpt balloon (n = 37). Stent expansion was defined as the ratio of intravascular ultrasound-measured minimum stent diameter and minimum stent area to the manufacturer's predicted stent diameter and area. These ratios were larger after AngioSculpt predilation, and a greater percentage of stents had final minimum stent areas >5.0 mm(2) (another commonly accepted criterion of adequate DES expansion). Lesion morphology, stent and lesion length, and reference vessel size did not affect DES expansion. In conclusion, in this observational, nonrandomized study, pretreatment with the AngioSculpt balloon enhanced stent expansion and minimized the difference between predicted and achieved stent dimensions.

Arsenic trioxide eluting stent reduces neointima formation in a rabbit iliac artery injury model.

OBJECTIVE: In-stent restenosis is caused by the neointimal hyperplasia, which involves abnormal growth of vascular smooth muscle cells (VSMC). Arsenic trioxide (As2O3) is known to be a potent inhibitor of cell proliferation. We therefore studied the role of an As2O3 eluting stent in the prevention of restenosis in a rabbit iliac artery model. METHODS AND RESULTS: Bare stents, or stents coated with poly-L-lactic acid (PLLA) and either 40 microg of As2O3, 180 microg of paclitaxel or vehicle were implanted into the left proximal iliac arteries of New Zealand rabbits. The delivery of drugs from stents in vitro and in vivo was evaluated by atomic fluorescence spectrophotometry and high-performance liquid chromatography, respectively. Histomorphometric measurements at 7 or 28 days showed that, comparing to rabbits receiving the PLLA stent, in animals treated with As2O3 eluting or paclitaxel eluting stent neointima thickness was reduced by 50% and 46%, the absolute neointimal area was reduced by 53% and 44%, while the absolute luminal area was increased by 46% and 43%, respectively. There were no significant differences in injury or inflammation scores among PLLA, As2O3 eluting and paclitaxel eluting stents. As2O3 eluting stent induced more TUNEL-positiv VSMC than the other stents. As2O3 levels measured in the arterial tissue were much higher than those in serum, which were nearly undetectable at 7 days after stent implantation. In in vitro studies, cultured rabbit arterial VSMC were stimulated with As2O3 or paclitaxel and analyzed for their cell cycle progression and apoptosis by flow cytometry and electron microscopy. As2O3 treatment resulted in a reduction of VSMC number in G1 phase with a concomitant increase in apoptosis of VSMC, whereas paclitaxel treatment led to blocking of VSMC in the G2/M phase. CONCLUSION: In a rabbit iliac artery model PLLA coated As2O3 eluting stent significantly suppressed in-stent restenosis by reducing proliferation and inducing apoptosis of VSMC.

Nine-month angiographic and two-year clinical follow-up of novel biodegradable-polymer arsenic trioxide-eluting stent versus durable-polymer sirolimus-eluting stent for coronary artery disease.

BACKGROUND: Despite great reduction of in-stent restenosis, first-generation drug-eluting stents (DESs) have increased the risk of late stent thrombosis due to delayed endothelialization. Arsenic trioxide, a natural substance that could inhibit cell proliferation and induce cell apoptosis, seems to be a promising surrogate of sirolimus to improve DES performance. This randomized controlled trial was to evaluate the efficacy and safety of a novel arsenic trioxide-eluting stent (AES), compared with traditional sirolimus-eluting stent (SES). METHODS: Patients with symptoms of angina pectoris were enrolled and randomized to AES or SES group. The primary endpoint was target vessel failure (TVF), and the second endpoint includes rates of all-cause death, cardiac death or myocardial infarction, target lesion revascularization (TLR) by telephone visit and late luminal loss (LLL) at 9-month by angiographic follow-up. RESULTS: From July 2007 to 2009, 212 patients were enrolled and randomized 1:1 to receive either AES or SES. At 2 years of follow-up, TVF rate was similar between AES and SES group (6.67% vs. 5.83%, P = 0.980). Frequency of all-cause death was significantly lower in AES group (0 vs. 4.85%, P = 0.028). There was no significant difference between AES and SES in frequency of TLR and in-stent restenosis, but greater in-stent LLL was observed for AES group (0.29 ± 0.52 mm vs. 0.10 ± 0.25 mm, P = 0.008). CONCLUSIONS: After 2 years of follow-up, AES demonstrated comparable efficacy and safety to SES for the treatment of de novo coronary artery lesions.

Sirolimus-eluting stents in real-world patients with ST-segment elevation acute myocardial infarction.

Recently, the use of sirolimus-eluting stents (SES) has been demonstrated to significantly reduce the rate of adverse events among selected patients with ST-segment elevation acute myocardial infarction (STEMI). We present real-world experience from a single center registry evaluating the safety and efficacy of primary percutaneous coronary intervention (PCI) in unselected patients with STEMI using SES. Clinical outcome at 300-day follow-up in two cohorts of 225 consecutive patients who underwent bare metal stent (BMS) (January 2004-February 2005, n = 123) or SES (March 2005-December 2006, n = 102) implantation was examined. The primary endpoint was a composite of major adverse cardiovascular events (MACE: death, nonfatal reinfarction, and target vessel revascularization [TVR]). The incidence of short-term MACE was similar between the SES group and BMS group (30-day rate of MACE: 4.9% versus 8.9%, P = 0.30). Angiographically documented stent thrombosis within 30 days after primary PCI was not diagnosed in any patient in the SES group and occurred in 1 patient treated with BMS (0 versus 0.8%, P = 1.0). At 300 days, SES implantation significantly reduced the incidence of MACE (7.8% versus 22.8%, hazard ratio [HR] 0.32 [95% confidence interval (CI) 0.15 to 0.71], P = 0.005), mainly due to a marked reduction in the risk of TVR (1.0% versus 17.1%, HR 0.05 [95% CI 0.01 to 0.39], P < 0.001). There was no new onset of documented stent thrombosis between 30 and 300 days in either group. Thus, this real-world registry confirmed the safety and efficacy of SES with remarkably lower rates of TVR and MACE in the setting of primary PCI for unselected patients with STEMI in a real-world scenario.

Effectiveness and safety of the sirolimus-eluting stents coated with bioabsorbable polymer coating in human coronary arteries.

BACKGROUND: Although the sirolimus-eluting stent (CYPHER, Cordis, USA) has shown a dramatic reduction of restenosis, there are still some concerns about its efficacy and safety. Its durable polymer coating may enhance neointimal proliferation and residual sirolimus, which cannot be released from polymer, may result in incomplete reendothelization. As a drug reservoir, bioabsorbable polymer (polylactic acid, PLA) is more rational. OBJECTIVE: We aimed to determine the safety and efficacy of sirolimus-eluting stent coated with PLA (EXCEL, JW Medical Systems, China) in the treatment of human coronary arterial diseases. METHODS: The study included 31 patients with de novo coronary lesions, with vessels 2.5-3.5 mm in diameter. The primary end points included the percentage of in-stent restenosis of the luminal diameter and in-stent late luminal loss at 6 months, as determined by quantitative angiography. The secondary end point was the major adverse cardiac events (MACE) 30 days and 6 months after the index procedure. RESULTS: Forty-eight EXCEL stents were successfully delivered in the 34 lesions, and multiple stents were implanted in 35.3% of lesions. All patients were discharged without clinical complications and completed clinical follow-up at 1 and 6 months. No MACE had occurred. Twenty patients (30 stents) completed 6 months of angiographic follow-up. No in-stent or in-lesion restenosis (diameter stenosis > or =50%) was observed. In-stent late loss was (0.07 +/- 0.17) mm. CONCLUSIONS: The implantation of EXCEL stent is feasible and safe and elicits minimal neointimal proliferation. This new stent has potential advantages regarding the long-long-term result over the commercially stent as the new stent has no sustained stimulation to the local tissue.