This study combined the herbal pair Platycodonis Radix-Curcumae Rhizoma(PR-CR) possessing an inhibitory effect on tumor cell proliferation and metastasis with the active component of traditional Chinese medicine(TCM) silibinin-loaded nanoparticles(NPs) with a regulatory effect on tumor microenvironment based on the joint effect on tumor cells and tumor microenvironment to inhi-bit cell metastasis. The effects of PR-CR on the cellular uptake of NPs and in vitro inhibition against breast cancer proliferation and metastasis were investigated to provide an experimental basis for improving nanoparticle absorption and enhancing therapeutic effects. Silibinin-loaded lipid-polymer nanoparticles(LPNs) were prepared by the nanoprecipitation method and characterized by transmission electron microscopy. The NPs were spherical or quasi-spherical in shape with obvious core-shell structure. The mean particle size was 107.4 nm, Zeta potential was-27.53 mV. The cellular uptake assay was performed by in vitro Caco-2/E12 coculture cell model and confocal laser scanning microscopy(CLSM), and the results indicated that PR-CR could promote the uptake of NPs. Further, in situ intestinal absorption assay by the CLSM vertical scanning approach showed that PR-CR could promote the absorption of NPs in the enterocytes of mice. The inhibitory effect of NPs on the proliferation and migration of 4T1 cells was analyzed using 4T1 breast cancer cells and co-cultured 4T1/WML2 cells, respectively. The results of the CCK8 assay showed that PR-CR-containing NPs could enhance the inhibition against the proliferation of 4T1 breast cancer cells. The wound healing assay indicated that PR-CR-containing NPs enhanced the inhibition against the migration of 4T1 breast cancer cells. This study enriches the research on oral absorption of TCM NPs and also provides a new idea for utilizing the advantages of TCM to inhibit breast cancer metastasis.
Humans ; Mice ; Animals ; Female ; Silybin/therapeutic use* ; Caco-2 Cells ; Polymers/chemistry* ; Nanoparticles/chemistry* ; Cell Line, Tumor ; Breast Neoplasms/pathology* ; Tumor Microenvironment

BACKGROUNDDespite 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).

METHODSPatients 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.

RESULTSFrom 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).

CONCLUSIONSAfter 2 years of follow-up, AES demonstrated comparable efficacy and safety to SES for the treatment of de novo coronary artery lesions.

Aged ; Arsenicals ; administration & dosage ; therapeutic use ; Coronary Angiography ; Coronary Artery Disease ; diagnostic imaging ; surgery ; Drug-Eluting Stents ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Oxides ; administration & dosage ; therapeutic use ; Percutaneous Coronary Intervention ; methods ; Polymers ; chemistry ; Sirolimus ; administration & dosage ; therapeutic use

The core-crosslinked polymeric micelles were used as a new drug delivery system, which can decrease the premature drug release in blood circulation, improve the stability of the micelles, and effectively transport the drug into the therapy sites. Then the drug bioavailability increased further, while the side effect reduced. Most drugs were physically entrapped or chemically covalent with the polymer in the internals of micelles. Based on the various constitutions and properties of polymeric micelles as well as the special characteristics of body microenvironment, the environment-responsive or active targeting core-crosslinked micelles were designed and prepared. As a result, the drug controlled release behavior was obtained. In the present paper, the research progress of all kinds of core-crosslinked micelles which were published in recent years is introduced. Moreover, the characteristic and application prospect of these micelles in drug delivery system are analyzed and summarized.
Animals ; Antineoplastic Agents ; administration & dosage ; chemistry ; therapeutic use ; Cross-Linking Reagents ; chemistry ; metabolism ; Drug Carriers ; chemistry ; metabolism ; Humans ; Micelles ; Molecular Structure ; Neoplasms ; drug therapy ; Particle Size ; Pharmaceutical Preparations ; administration & dosage ; Polyethylene Glycols ; chemistry ; metabolism ; Polymers ; chemistry ; metabolism

Drug-Eluting Stents ; Humans ; Polymers ; chemistry ; therapeutic use ; Sirolimus ; therapeutic use

BACKGROUNDDrug-eluting stents (DES) with durable polymer have significantly reduced restenosis and target vessel revascularization compared with bare metal stents. Durable polymer has been linked with persistent inflammation of vessel wall and delayed endothelial healing that may increase the risk of late and very late stent thrombosis. This study sought to evaluate the efficacy and safety of HELIOS completed biodegradable polymer sirolimus-eluting stent (SES) in de novo coronary lesions.

METHODSTotally, 287 patients with one or two de novo coronary lesions (lesion length ≤ 38 mm and reference vessel diameter 2.5-4.0 mm) were enrolled in the HOPE study, a prospective, multicenter, randomized, non-inferiority trial. Patients were randomized to treatment either with HELIOS completed biodegradable polymer SES (n = 142) or PARTNER durable polymer SES (n = 145). The primary endpoint was angiographic in-stent late lumen loss (LLL) at 9-month follow-up. The secondary endpoint included stent thrombosis and major adverse cardiac events including cardiac death, myocardial infarction (MI) and target lesion revascularization (TLR).

RESULTSThe 9-month in-stent LLL in the HELIOS group was similar to the PARTNER group, (0.16 ± 0.22) mm vs. (0.19 ± 0.30) mm (P = 0.28). The difference and 95% confidence interval were -0.03 (-0.09, 0.04), and the P value for non-inferiority <0.01. Major adverse cardiovascular event (MACE) occurred in 7.9% vs. 8.2%, MI in 2.4% vs. 3.0%, TLR in 5.5% vs. 3.0%, and stent thrombosis in 0 vs. 1.5%; and events were comparable between the HELIOS group and PARTNER group at three-year follow-up (all P > 0.05). The three-year cardiac death was lower in the HELIOS group, but with no significant difference, 0 vs. 3.0% (P = 0.12).

CONCLUSIONSIn the HOPE trial, the novel completed biodegradable polymer SES HELIOS was non-inferior to the durable polymer SES PARTNER with respect to nine-month in-stent LLL in de novo coronary lesions. The incidence of other clinical endpoints was low for both of the stents in three-year follow-up.

Adult ; Aged ; Angiography ; Coronary Artery Disease ; surgery ; Coronary Restenosis ; prevention & control ; Drug-Eluting Stents ; Humans ; Middle Aged ; Percutaneous Coronary Intervention ; Polymers ; chemistry ; therapeutic use ; Sirolimus ; therapeutic use ; Titanium ; chemistry ; Treatment Outcome ; Young Adult

BACKGROUNDIn the TARGET I randomized controlled trial, the novel abluminal groove-filled biodegradable polymer sirolimus-eluting stent FIREHAWK proved non-inferior to the everolimus-eluting stent in nine-month in-stent late loss in single de novo coronary lesions. This study was aimed at evaluating clinical safety and effectiveness of FIREHAWK in a moderately complex population (including patients with small vessels, long lesions and multi-vessels), and at validating the ability of the SYNTAX score (SS) to predict clinical outcomes in patients treated with this latest generation drug-eluting stent.

METHODSTARGET II was a prospective, multicenter, single-arm study with primary outcome of 12-month target lesion failure (TLF), including cardiac death, target vessel myocardial infarction (TV-MI) and ischemia-driven target lesion revascularization (TLR). Stent thrombosis was defined according to the Academic Research Consortium (ARC) definition. Patients were grouped by tertiles of SS (≤6, >6 to ≤12, and >12). All patients were exclusively treated with the FIREHAWK stent and were followed up at 1, 6, and 12 months, and annually thereafter up to five years.

RESULTSA total of 730 patients were included in this registry study. The 12-month incidence of TLF was 4.4% and the incidence of TLF components were, cardiac death 0.5%, TV-MI 3.2%, and TLR 2.2%. One definite/probable stent thrombosis was observed at 12-month follow-up. Mean SS was 10.87±6.87. Patients in the SS >12 tertile had significantly higher TLF (P = 0.02) and TLR (P < 0.01) rates than those in lower SS groups. In COX proportional-hazards regression analyses, TLF incidence was strongly related to lesion length (long lesion vs. non-long lesion patients; HR 3.416, 95% CI, 1.622-7.195), but unrelated to diabetic, small vessel, and multivessel subgroups.

CONCLUSIONSThe low TLF incidence in this study indicates that FIREHAWK is safe and effective in the treatment of moderately complex coronary disease. SS is also able to predict adverse clinical outcomes in FIREHAWK treated patients.

Adolescent ; Adult ; Aged ; Biocompatible Materials ; chemistry ; Cardiovascular Agents ; therapeutic use ; Coronary Stenosis ; drug therapy ; therapy ; Coronary Vessels ; pathology ; Drug-Eluting Stents ; Female ; Humans ; Male ; Middle Aged ; Percutaneous Coronary Intervention ; Polymers ; Proportional Hazards Models ; Sirolimus ; therapeutic use ; Young Adult

BACKGROUNDDrug-eluting stents represent a major advance in interventional cardiology. However, the current drug-eluting stents have significant limitations. One of the major problems is very late stent thrombosis, which is likely caused by inflammation and a hypersensitivity reaction related to a polymer on the stent. A polymer-free sirolimus-eluting stent with a unique nano-porous surface has been developed. This study aimed to evaluate this novel polymer-free sirolimus-eluting stent for its efficacy and safety in a pig model.

METHODSStents were directly coated with sirolimus (a drug concentration of 2.2 µg/mm(2) on the stent surface). The polymer-free sirolimus-eluting stents (PFSES) were compared to standard polymer-coated sirolimus-eluting stents (PCSES) and bare-metal stents (BMS) in 18 pigs.

RESULTSAt one month the degree of neointimal hyperplasia was similar between the two sirolimus-eluting stent groups and was significantly less compared to BMS ((1.93 ± 0.51) mm(2), (1.57 ± 0.69) mm(2) vs. (4.45 ± 1.05) mm(2), P < 0.05) At three months, PFSES maintained the low level of neointima ((2.41 ± 0.99) mm(2) vs. (4.32 ± 1.16) mm(2), P < 0.05), whereas PCSES had developed significant neointimal proliferation similar to BMS. The inflammation level was significantly higher in PCSES when compared with BMS three months post-implantation (2.50 ± 0.55 vs. 0.83 ± 0.75, P < 0.05) whereas PFSES showed a low level of inflammation comparable to PCSES (1.33 ± 0.52 vs. 2.50 ± 0.55, P < 0.05).

CONCLUSIONThe PFSES is effective and safe, and appears to be superior to standard PCSEs.

Animals ; Drug-Eluting Stents ; adverse effects ; Neointima ; prevention & control ; Polymers ; chemistry ; Sirolimus ; therapeutic use ; Swine

Animals ; Coronary Vessels ; surgery ; Drug-Eluting Stents ; adverse effects ; Lactic Acid ; chemistry ; Polyesters ; Polymers ; chemistry ; Sirolimus ; chemistry ; therapeutic use ; Swine

BACKGROUNDSirolimus-eluting stents (SES) are reported to be associated with reduced late lumen loss (LLL), resulting in less frequent restenosis when compared to bare-metal stent. The current study aimed to assess the difference in LLL between SES with biodegradable and with permanent polymer.

METHODSFrom March 2010 to June 2011, 300 consecutive patients having only biodegradable polymers or permanent polymer SES for all diseased vessels were included. Serial quantitative coronary analysis was performed on both the "in-stent" and "segment" area, including the stented segment, as well as both five mm margins proximal and distal to the stent. The primary endpoint was the LLL defined as the minimal lumen diameter (MLD) post-stenting minus the MLD at nine-month after the indexed procedure.

RESULTSLLL was comparable between the two stents. Importantly, LLL for the distal segment (median 0.05 mm, interquartile 0 to 0.09 mm) was less severe compared with in-stent (median 0.13 mm, interquartile 0.08 to 0.18 mm) and proximal segment LLL (median 0.12 mm, interquartile 0.06 to 0.14 mm, all P < 0.001). In general, the LLL was associated with the post-procedure MLD (b = 0.28, P = 0.002), hyperlipidemia (b = 0.14, P = 0.021), and calcified lesions (b = 0.58, P = 0.001). The R(2) and Radj of the multiple regression model were 0.651 and 0.625, respectively.

CONCLUSIONSSES with either biodegradable or permanent polymer had lower value of LLL. The small amount of LLL at the distal segment possibly contributed to the less distal edge stenosis.

Aged ; Aspirin ; therapeutic use ; Coronary Restenosis ; prevention & control ; Drug-Eluting Stents ; Female ; Humans ; Male ; Middle Aged ; Polymers ; chemistry ; Regression Analysis ; Sirolimus ; therapeutic use ; Ticlopidine ; analogs & derivatives ; therapeutic use

BACKGROUNDThe gender difference on long-term outcome in unselected patients after percutaneous coronary intervention (PCI) has not yet been fully investigated. This study aimed to evaluate the gender difference on five-year outcomes following EXCEL biodegradable polymer-coated sirolimus-eluting stenting in patients with coronary disease.

METHODSA total of 2077 "all comers", consisting of 1528 (73.6%) men and 549 (26.4%) women, who were exclusively treated with EXCEL coronary stents were enrolled in the prospective CREATE study at 59 centers from four countries. After propensity score matching, the baseline characteristics of the two groups were well matched. Recommended antiplatelet regimen was clopidogrel and aspirin for six months followed by chronic aspirin therapy. The primary outcome that was the rate of major adverse cardiac events (MACE), defined as a composite of cardiac mortality, non-fatal myocardial infarction (MI) and target lesion revascularization (TLR), and stent thrombosis (ST) at five years were compared between the two gender groups.

RESULTSIn the two groups, women had higher proportions of clinical risk factors, such as being elderly, diabetes mellitus, hypertension and hyperlipidemia, compared to men. Besides, the mean target vessel number per patient was higher and the mean reference vessel diameter smaller for women. Men had higher risks of cardiac death (3.7% vs. 1.6%, P = 0.021) and MACE (8.4% vs. 4.7%, P = 0.004) at five years compared with women. However, the cumulative hazards of non-fatal MI and TLR were similar between men and women. The incidence of Academic Research Consortium (ARC) definite or probable stent thrombosis was similar between the two groups (1.3% vs. 1.0%, P = 0.639). Prolonged clopidogrel therapy (>6 months) did not reduce the cumulative hazards of ST from six months to five years in both men (χ(2) = 0.098, log rank P = 0.754) and women (χ(2) = 2.043, log rank P = 0.153) patients.

CONCLUSIONSWomen had a lower MACE and cardiac death rate than men after biodegradable polymer-coated sirolimus-eluting stenting in long term follow-up. Effects of prolonged dual antiplatelet therapy (DAPT) in preventing stent thrombosis was similar with six-month DAPT after EXCEL stent implantation in both men and women groups.

Aged ; Angioplasty, Balloon, Coronary ; methods ; Coronary Angiography ; Drug-Eluting Stents ; Female ; Humans ; Male ; Middle Aged ; Polymers ; chemistry ; Prospective Studies ; Sex Factors ; Sirolimus ; therapeutic use ; Treatment Outcome