Dual drug-loaded polymeric mixed micelles for ovarian cancer: Approach to enhanced therapeutic efficacy of albendazole and paclitaxel.

Chemotherapy resistance remains a significant challenge in treating ovarian cancer effectively. This study addresses this issue by utilizing a dual drug-loaded nanomicelle system comprising albendazole (ABZ) and paclitaxel (PTX), encapsulated in a novel carrier matrix of D-tocopheryl polyethylene glycol 1000 succinate vitamin E (TPGS), soluplus and folic acid. Our objective was to develop and optimize this nanoparticulate delivery system using solvent evaporation techniques to enhance the therapeutic efficacy against ovarian cancer. The formulation process involved pre-formulation, formulation, optimization, and comprehensive characterization of the micelles. Optimization was conducted through a 32 factorial design, focusing on the effects of polymer ratios on particle size, zeta potential, polydispersity index (PDI) and entrapment efficiency (%EE). The optimal formulation demonstrated improved dilution stability, as indicated by a critical micelle concentration (CMC) of 0.0015 mg/mL for the TPGS-folic acid conjugate (TPGS-FOL). Extensive characterization included differential scanning calorimetry (DSC), nuclear magnetic resonance (NMR), and Fourier-transform infrared spectroscopy (FTIR). The release profile exhibited an initial burst followed by sustained release over 90 h. The cytotoxic potential of the formulated micelles was superior to that of the drugs alone, as assessed by MTT assays on SKOV3 ovarian cell lines. Additionally, in vivo studies confirmed the presence of both drugs in plasma and tumour tissues, suggesting effective targeting and penetration. In conclusion, the developed TPGS-Fol-based nanomicelles for co-delivering ABZ and PTX show promising results in overcoming drug resistance, enhancing solubility, sustaining drug release, and improving therapeutic outcomes in ovarian cancer treatment.

A registry-based study of paclitaxel drug-coated balloon angioplasty for the treatment of in-stent restenosis of the femoral-popliteal artery.

OBJECTIVE: The aim of this study was to report the results of a prospective, single-arm, registry-based study assessing the safety and performance of a paclitaxel drug-coated balloon (DCB) for the treatment of superficial femoral artery (SFA) or popliteal artery in-stent restenosis (ISR) in a United States population. METHODS: We conducted a prospective, non-randomized, multi-center, single-arm, post-market registry of the IN.PACT Admiral DCB for the treatment of ISR lesions in the SFA or popliteal artery at 43 sites within the Society for Vascular Surgery (SVS) Vascular Quality Initiative (VQI) Registry from December 2016 to January 2020. Clinical outcomes were assessed at 12, 24, and 36 months. The primary endpoint was target lesion revascularization at 12 months. Secondary endpoints included technical success, target vessel revascularization, major limb amputation, and all-cause mortality. Results are presented as survival probabilities based on Kaplan-Meier survival estimates. RESULTS: Patients (N = 300) were 58% male, with a mean age of 68 ± 10 years. Diabetes was present in 56%, 80% presented with claudication, and 20% with rest pain. Lesions included ISR of the SFA in 68%, SFA-popliteal in 26%, and popliteal arteries in 7%. The mean lesion length was 17.8 ± 11.8 cm. Lesions were categorized as occlusions in 43% (mean occluded length, 16 ± 10 cm). TASC type was A (17%), B (29%), C (38%), and D (15%). Technical success was 99%. Re-stenting was performed in 5% and thrombolysis in 0.6% of patients. Kaplan-Meier estimates for freedom from target lesion revascularization were 90%, 72%, and 62% at 12, 24, and 36 months. Freedom from target vessel revascularization was 88%, 68%, and 59% and freedom from major target limb amputation was 99.6%, 98.9%, and 98.9%, respectively, at 12, 24, and 36 months. Survival was 95%, 89%, and 85% at 12, 24, and 36 months. CONCLUSIONS: This post-market registry-based study shows promising results in treating femoral-popliteal ISR with paclitaxel DCB in comparison to the results of plain balloon angioplasty reported in the literature. These results demonstrate the ability of the SVS VQI to conduct post-market evaluation of peripheral devices in partnership with industry and federal regulators.

Paclitaxel liposome (Lipusu) based chemotherapy combined with immunotherapy for advanced non-small cell lung cancer: a multicenter, retrospective real-world study.

BACKGROUND: Paclitaxel liposome (Lipusu) is known to be effective in non-small cell lung cancer (NSCLC) as first-line treatment. This study aimed to evaluate the effectiveness and safety of paclitaxel liposome based chemotherapy plus PD-1/PD-L1 inhibitor in patients with advanced NSCLC. METHODS: In this multicenter, retrospective, real-world study, patients with advanced NSCLC who were administered paclitaxel liposome based chemotherapy plus PD-1/PD-L1 inhibitor in three centers (Peking University People's Hospital as the lead center) in China between 2016 and 2022 were included. Progression-free survival (PFS), overall survival (OS), objective response rate, disease control rate, and adverse events (AEs) were evaluated. RESULTS: A total of 49 patients were included, with 33 (67.3%) receiving paclitaxel liposome based chemotherapy plus PD-1/PD-L1 inhibitor as first-line treatment. There were 34 patients (69.4%) diagnosed with squamous cell carcinoma and 15 (30.6%) with adenocarcinoma. The median follow-up was 20.5 (range: 3.1-41.1) months. The median PFS and OS of all patients were 9.7 months (95% confidence interval [CI], 7.0-12.4) and 30.5 months (95% CI, not evaluable-not evaluable), respectively. Patients with squamous cell carcinoma and adenocarcinoma had median PFS of 11 months (95%CI, 6.5-15.5) and 9.3 months (95%CI, 7.0-12.4), respectively. The median PFS was 9.9 months (95%CI, 7.1-12.7) in patients who received the combined regimen as first-line treatment. Treatment-related AEs of any grade were observed in 25 (51.0%) patients, and AEs of grade 3 or worse were observed in nine patients (18.4%). The most common treatment-related AEs were myelosuppression (14.3%) and fever (10.2%). CONCLUSIONS: Paclitaxel liposome based chemotherapy plus PD-1/PD-L1 inhibitor prolonged the PFS in advanced NSCLC with acceptable safety, which was worthy of clinical application.

Impact of previous S-1 treatment on efficacy of liposomal irinotecan plus 5-fluorouracil and leucovorin in patients with metastatic pancreatic cancer.

BACKGROUND/OBJECTIVES: Liposomal irinotecan plus 5-fluorouracil and leucovorin (nal-IRI + 5-FU/LV) provides survival benefits for metastatic pancreatic adenocarcinoma (mPDAC) refractory to gemcitabine-based treatment, mainly gemcitabine plus nab-paclitaxel (GA), in current practice. Gemcitabine plus S-1 (GS) is another commonly administered first-line regimen before nab-paclitaxel reimbursement; however, the efficacy and safety of nal-IRI + 5-FU/LV for mPDAC after failed GS treatment has not been reported and was therefore explored in this study. METHODS: In total, 177 patients with mPDAC received first-line GS or GA treatment, followed by second-line nal-IRI + 5-FU/LV treatment (identified from a multicenter retrospective cohort in Taiwan from 2018 to 2020); 85 and 92 patients were allocated to the GS and GA groups, respectively. Overall survival (OS), time-to-treatment failure (TTF), and adverse events were compared between the two groups. RESULTS: The baseline characteristics of the two groups were generally similar; however, a higher median age (67 versus 62 years, p < 0.001) and fewer liver metastases (52% versus 78%, p < 0.001) were observed in the GS versus GA group. The median OS was 15.0 and 15.9 months in the GS and GA groups, respectively (p = 0.58). The TTF (3.1 versus 2.8 months, p = 0.36) and OS (7.6 versus 6.7 months, p = 0.83) after nal-IRI treatment were similar between the two groups. More patients in the GS group developed mucositis during nal-IRI treatment (15% versus 4%, p = 0.02). CONCLUSIONS: The efficacy of second-line nal-IRI +5-FU/LV treatment was unaffected by prior S-1 exposure. GS followed by nal-IRI treatment is an alternative treatment sequence for patients with mPDAC.

Drug-coated balloon therapy for in-stent restenosis in patients with iliofemoral deep vein thrombosis: A single-arm observational study.

BACKGROUND: Iliofemoral deep vein thrombosis (IFDVT) causes severe symptoms and affect the quality of life to a great extent. Endovascular thrombectomy and stent implantation have been a feasible strategie to alleviate the signs and symptoms of IFDVT. However, venous in-stent restenosis (ISR) has become an emerging non-negligible problem. METHODS: To evaluate the histological characteristics of venous ISR, neointima of arterial and venous ISR patients were collected and examed. To explore the effect of drug-coated balloon (DCB) on venous ISR lesions, we conducted a single-center retrospective case series study involving IFDVT patients with ISR after venous stenting who were treated with paclitaxel-coated balloon dilatation. RESULTS: We found a collagen-rich matrix but not elastin, as well as fewer cells and less neovascularization in venous intimal hyperplasia compared with neointima in arteries. Thirteen IFDVT patients were involved in the study, with average preoperative stenosis degree of 87.69% ± 13.48%. After intervention, the stenosis degree was significantly reduced to 14.6% ± 14.36% immediately (p < 0.0001) and to 16.54% ± 15.73% during follow-up (p < 0.0001). During follow-up, the VEINES-QOL scores (p < 0.0001), VEINES-Sym scores (p < 0.0001), and Villalta scores (p = 0.04) of patients was improved significantly compared with those before intervention. No major adverse events were observed. CONCLUSIONS: The use of DCB may have a positive effect in the treatment of venous ISR by targeting intimal hyperplasia. Moreover, the application of DCB dilatation in IFDVT stenting patients with ISR is deemed safe and effective.

Self-Assembled Micelles Based on Ginsenoside Rg5 for the Targeted Treatment of PTX-Resistant Tumors.

Paclitaxel (PTX) is one of the first-line drugs for prostate cancer (PC) treatment. However, the poor water solubility, inadequate specific targeting ability, multidrug resistance, and severe neurotoxicity are far from being fully resolved, despite diverse PTX formulations in the market, such as the gold-standard PTX albumin nanoparticle (Abraxane) and polymer micelles (Genexol-PM). Some studies attempting to solve the multiple problems of chemotherapy delivery fall into the trap of an extremely complicated formulation design and sacrifice druggability. To better address these issues, this study designed an efficient, toxicity-reduced paclitaxel-ginsenoside polymeric micelle (RPM). With the aid of the inherent amphiphilic molecular structure and pharmacological effects of ginsenoside Rg5, the prepared RPM enhances the water solubility and active targeting of PTX, inhibiting chemotherapy resistance in cancer cells. Moreover, the polymeric micelles demonstrated favorable anti-inflammatory and neuroprotective effects, providing ideas for the development of new clinical anti-PC preparations.

Sialic Acid Conjugate-Modified Cationic Liposomal Paclitaxel for Targeted Therapy of Lung Metastasis in Breast Cancer: What a Difference the Cation Content Makes.

Cationic lipids play a pivotal role in developing novel drug delivery systems for diverse biomedical applications, owing to the success of mRNA vaccines against COVID-19 and the Phase III antitumor agent EndoTAG-1. However, the therapeutic potential of these positively charged liposomes is limited by dose-dependent toxicity. While an increased content of cationic lipids in the formulation can enhance the uptake and cytotoxicity toward tumor-associated cells, it is crucial to balance these advantages with the associated toxic side effects. In this work, we synthesized the cationic lipid HC-Y-2 and incorporated it into sialic acid (SA)-modified cationic liposomes loaded with paclitaxel to target tumor-associated immune cells efficiently. The SA-modified cationic liposomes exhibited enhanced binding affinity toward both RAW264.7 cells and 4T1 tumor cells in vitro due to the increased ratios of cationic HC-Y-2 content while effectively inhibiting 4T1 cell lung metastasis in vivo. By leveraging electrostatic forces and ligand-receptor interactions, the SA-modified cationic liposomes specifically target malignant tumor-associated immune cells such as tumor-associated macrophages (TAMs), reduce the proportion of cationic lipids in the formulation, and achieve dual objectives: high cellular uptake and potent antitumor efficacy. These findings highlight the potential advantages of this innovative approach utilizing cationic liposomes.

Difference in one-year late lumen loss between high- and low-dose paclitaxel-coated balloons for femoropopliteal disease.

The objective of the study is to investigate the difference in 1-year late lumen loss (LLL) between the high- (IN.PACT Admiral) and low-dose (Lutonix) paclitaxel-coated balloon (PCB). Although a recent randomized clinical trial demonstrated no difference in efficacy endpoint between high- and low-dose PCB, it remains unclear whether high-dose PCB was superior to low-dose PCB in actual clinical practice. We enrolled 64 patients with 67 de novo femoropopliteal lesions who underwent PCB angioplasty at Kokura Memorial Hospital from May 2014 to March 2020 and subsequent follow-up angiography after 1 year. The primary endpoint was 1-year LLL, whereas the secondary endpoints were binary restenosis and clinically driven target lesion revascularization (CD-TLR) after 1 year. The high- and low-dose PCB groups had 45 and 22 lesions, respectively. Although the low-dose PCB group had higher rates of coronary artery disease, hemodialysis, and chronic limb-threatening ischemia than the high-dose PCB group, the latter had a longer lesion length and more lesions with a TASC classification C or D than the former. The high-dose PCB group had a significantly lower LLL than the low-dose PCB group (0.40 ± 1.05 vs. 1.19 ± 1.03 mm; P = 0.003, respectively). Moreover, the high-dose PCB group had significantly lower rates of binary restenosis at 1 year than the low-dose PCB group (22.2% vs. 50.0%; P = 0.02, respectively). Moreover, negative LLL was only observed in the high-dose PCB group (33.3% vs. 0%, P = 0.005). The high-dose PCB group had a significantly lower LLL than the low-dose PCB group.

Treatment of Hemodialysis Vascular Access Repeated Stenosis with Paclitaxel-Coated Balloon Angioplasty: A Retrospective Study.

INTRODUCTION: The objective of this study was to report our experience of angioplasty with paclitaxel-coated balloon (PCB) versus common balloon (CB) for the treatment of repeated failing vascular access. METHODS: Retrospective, single-center analysis consisting of 88 patients treated with percutaneous transluminal angioplasty in the period from October 2020 through December 2021. Patients were divided into two groups according to the type of treatment as PCB (n = 41) and CB (n = 47). We analyzed target lesion primary patency and vascular access primary patency for 6 months and the rate of complications. RESULTS: There was no significant difference in the target lesion primary patency which was similar for 6 months between the two groups (PCB group vs. CB group at 1, 3, and 6 months; 95.12 vs. 89.36% (p = 0.55), 75.61 versus 74.47% (p = 0.90), 53.66% versus 63.83% (p = 0.33), respectively). Similarly, vascular access primary patency in the PCB group and CB group was 90.24 and 89.36% (p = 0.83), respectively, at 1 month, 65.85 and 68.09% (p = 0.82), respectively, at 3 months, 39.02 and 53.19% (p = 0.18), respectively, at 6 months. There were no major complications after endovascular treatment. CONCLUSION: Compared to CB angioplasty, PCB angioplasty has no short-term patency benefit in the treatment of vascular access repeated stenosis.

Innovative strategies for effective paclitaxel delivery: Recent developments and prospects.

PURPOSE: Paclitaxel is an effective chemotherapeutic agent against a variety of cancer types. However, the clinical utility of paclitaxel is restricted by its poor solubility in water and high toxicity, resulting in low drug tolerance. These difficulties could be resolved by using suitable pharmacological carriers. Hence, it is essential to determine innovative methods of administering this effective medication to overcome paclitaxel's inherent limitations. METHODS: An extensive literature search was conducted using multiple electronic databases to identify relevant studies published. RESULTS: In this comprehensive analysis, many different paclitaxel delivery systems are covered and discussed, such as albumin-bound paclitaxel, polymeric micelles, paclitaxel-loaded liposomes, prodrugs, cyclodextrins, and peptide-taxane conjugates. Moreover, the review also covers various delivery routes of conventional paclitaxel or novel paclitaxel formulations, such as oral administration, local applications, and intraperitoneal delivery. CONCLUSION: In addition to albumin-bound paclitaxel, polymeric micelles appear to be the most promising formulations for innovative drug delivery systems at present. A variety of variants of polymeric micelles are currently undergoing advanced phases of clinical trials.

Riboflavin-targeted polymers improve tolerance of paclitaxel while maintaining therapeutic efficacy.

Active targeting can enhance precision and efficacy of drug delivery systems (DDS) against cancers. Riboflavin (RF) is a promising ligand for active targeting due to its biocompatibility and high riboflavin-receptor expression in cancers. In this study, RF-targeted 4-arm polyethylene glycol (PEG) stars conjugated with Paclitaxel (PTX), named PEG PTX RF, were evaluated as a targeted DDS. In vitro, PEG PTX RF exhibited higher toxicity against tumor cells compared to the non-targeted counterpart (PEG PTX), while free PTX displayed the highest acute toxicity. In vivo, all treatments were similarly effective, but PEG PTX RF-treated tumors showed fewer proliferating cells, pointing to sustained therapy effects. Moreover, PTX-treated animals' body and liver weights were significantly reduced, whereas both remained stable in PEG PTX and PEG PTX RF-treated animals. Overall, our targeted and non-targeted DDS reduced PTX's adverse effects, with RF targeting promoted drug uptake in cancer cells for sustained therapeutic effect.

Nanotechnology-Based Strategy for Enhancing Therapeutic Efficacy in Pancreatic Cancer: Receptor-Targeted Drug Delivery by Somatostatin Analog.

A novel nanotechnology-based drug delivery system (DDS) targeted at pancreatic cancer cells was developed, characterized, and tested. The system consisted of liposomes as carriers, an anticancer drug (paclitaxel) as a chemotherapeutic agent, and a modified synthetic somatostatin analog, 5-pentacarbonyl-octreotide, a ligand for somatostatin receptor 2 (SSTR2), as a targeting moiety for pancreatic cancer. The cellular internalization, cytotoxicity, and antitumor activity of the DDS were tested in vitro using human pancreatic ductal adenocarcinoma (PDAC) cells with different expressions of the targeted SSTR2 receptors, and in vivo on immunodeficient mice bearing human PDAC xenografts. The targeted drug delivery system containing paclitaxel exhibited significantly enhanced cytotoxicity compared to non-targeted DDS, and this efficacy was directly related to the levels of SSTR2 expression. It was found that octreotide-targeted DDS proved exceptionally effective in suppressing the growth of PDAC tumors. This study underscores the potential of octreotide-targeted liposomal delivery systems to enhance the therapeutic outcomes for PDAC compared with non-targeted liposomal DDS and Paclitaxel-Cremophor® EL, suggesting a promising avenue for future cancer therapy innovations.

Development of Aerosol Dry Powder Chemotherapeutic-Loaded Microparticles for the Treatment of Lung Cancer.

Lung cancer is the leading cause of cancer-related deaths worldwide, resulting in the highest mortality rates among both men and women with respect to all other types of cancer. Difficulties in treating lung cancer arise from late-stage diagnoses and tumor heterogeneity and current treatment involves a combination of chemotherapeutics, surgery, and radiation. Chemotherapeutics administered systemically can lead to undesirable side effects and severe off-site toxicity. For example, chronic administration of the chemotherapeutic doxorubicin (DOX) leads to cardiotoxicity, thereby limiting its long-term use. Systemic administration of the highly lipophilic molecule paclitaxel (PTX) is hindered by its water solubility, necessitating the use of solubilizing agents, which can induce side effects. Thus, in this investigation, formulations consisting of spray-dried microparticles (MP) containing DOX and PTX were produced to be administered as dry powder aerosols directly to the lungs. Acetalated dextran (Ac-Dex) was used as the polymer in these formulations, as it is a biocompatible and biodegradable polymer that exhibits pH-responsive degradation. Solid-state characterization revealed that DOX and PTX remained in solubility favoring amorphous states in the MP formulations and that both drugs remained thermally stable throughout the spray drying process. In vitro release studies demonstrated the pH sensitivity of the formulations due to the use of Ac-Dex, as well as the release of both therapeutics over the course of at least 48 h. In vitro aerosol dispersion studies demonstrated that both formulations exhibited suitable aerosol dispersion properties for deep lung delivery.

Integrated multi-omics analysis reveals unique signatures of paclitaxel-loaded poly(lactide-co-glycolide) nanoparticles treatment of head and neck cancer cells.

The use of poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) as carriers for chemotherapeutic drugs is regarded as an actively targeted nano-therapy for the specific delivery of anti-cancer drugs to target cells. However, the exact mechanism by which PLGA NPs boost anticancer cytotoxicity at the molecular level remains largely unclear. This study employed different molecular approaches to define the response of carcinoma FaDu cells to different types of treatment, specifically: paclitaxel (PTX) alone, drug free PLGA NPs, and PTX-loaded PTX-PLGA NPs. Functional cell assays revealed that PTX-PLGA NPs treated cells had a higher level of apoptosis than PTX alone, whereas the complementary, UHPLC-MS/MS (TIMS-TOF) based multi-omics analyses revealed that PTX-PLGA NPs treatment resulted in increased abundance of proteins associated with tubulin, as well as metabolites such as 5-thymidylic acid, PC(18:1(9Z)/18:1(9Z0), vitamin D, and sphinganine among others. The multi-omics analyses revealed new insights about the molecular mechanisms underlying the action of novel anticancer NP therapies. In particular, PTX-loaded NPs appeared to exacerbate specific changes induced by both PLGA-NPs and PTX as a free drug. Hence, the PTX-PLGA NPs' molecular mode of action, seen in greater detail, depends on this synergy that ultimately accelerates the apoptotic process, resulting in cancer cell death.

Randomized Trial of Chocolate Touch Compared With Lutonix Drug-Coated Balloon in Femoropopliteal Lesions (Chocolate Touch Study).

BACKGROUND: First-generation drug-coated balloons (DCBs) have significantly reduced the rate of restenosis compared with balloon angioplasty alone; however, high rates of bailout stenting and dissections persist. The Chocolate Touch DCB is a nitinol constrained balloon designed to reduce acute vessel trauma and inhibit neointima formation and restenosis. METHODS: Patients with claudication or ischemic rest pain (Rutherford class 2-4) and superficial femoral or popliteal disease (≥70% stenosis) were randomized 1:1 to Chocolate Touch or Lutonix DCB at 34 sites in the United States, Europe, and New Zealand. The primary efficacy end point was DCB success, defined as primary patency at 12 months (peak systolic velocity ratio <2.4 by duplex ultrasound without clinically driven target lesion revascularization in the absence of clinically driven bailout stenting). The primary safety end point was freedom from major adverse events at 12 months, a composite of target limb-related death, major amputation, or reintervention. Both primary end points were tested for noninferiority, and if met, sequential superiority testing for efficacy followed by safety was prespecified. An independent clinical events committee, and angiographic and duplex ultrasound core laboratories blinded to treatment allocation reviewed all end points. RESULTS: A total of 313 patients were randomized to Chocolate Touch (n=152) versus Lutonix DCB (n=161). Follow-up at 1 year was available in 94% of patients. The mean age was 69.4±9.5 years, the average lesion length was 78.1±46.9 mm, and 46.2% had moderate-to-severe calcification. The primary efficacy rates of DCB success at 12 months was 78.8% (108/137) with Chocolate Touch and 67.7% (88/130) with Lutonix DCB (difference, 11.1% [95% CI, 0.6-21.7]), meeting noninferiority (Pnoninferiority<0.0001) and sequential superiority (Psuperiority=0.04). The primary safety event rate was 88.9% (128/144) with Chocolate Touch and 84.6% (126/149) with Lutonix DCB (Pnoninferiority<0.001; Psuperiority=0.27). CONCLUSIONS: In this prospective, multicenter, randomized trial, the second-generation Chocolate Touch DCB met both noninferiority end points for efficacy and safety and was more effective than Lutonix DCB at 12 months for the treatment of femoropopliteal disease. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02924857.

Efficacy of a Drug-Eluting Stent Versus Bare Metal Stents for Symptomatic Femoropopliteal Peripheral Artery Disease: Primary Results of the EMINENT Randomized Trial.

BACKGROUND: A clear patency benefit of a drug-eluting stent (DES) over bare metal stents (BMSs) for treating peripheral artery disease of the femoropopliteal segment has not been definitively demonstrated. The EMINENT study (Trial Comparing Eluvia Versus Bare Metal Stent in Treatment of Superficial Femoral and/or Proximal Popliteal Artery) was designed to evaluate the patency of the Eluvia DES (Boston Scientific, Marlborough, MA), a polymer-coated paclitaxel-eluting stent, compared with BMSs for the treatment of femoropopliteal artery lesions. METHODS: EMINENT is a prospective, randomized, controlled, multicenter European study with blinded participants and outcome assessment. Patients with symptomatic peripheral artery disease (Rutherford category 2, 3, or 4) of the native superficial femoral artery or proximal popliteal artery with stenosis ≥70%, vessel diameter of 4 to 6 mm, and total lesion length of 30 to 210 mm were randomly assigned 2:1 to treatment with DES or BMS. The primary effectiveness outcome was primary patency at 12 months, defined as independent core laboratory-assessed duplex ultrasound peak systolic velocity ratio ≤2.4 in the absence of clinically driven target lesion revascularization or surgical bypass of the target lesion. Primary sustained clinical improvement was a secondary outcome defined as a decrease in Rutherford classification of ≥1 categories compared with baseline without a repeat target lesion revascularization. Health-related quality of life and walking function were assessed. RESULTS: A total of 775 patients were randomly assigned to treatment with DES (n=508) or commercially available BMSs (n=267). Baseline clinical, demographic, and lesion characteristics were similar between the study groups. Mean lesion length was 75.6±50.3 and 72.2±47.0 mm in the DES and BMS groups, respectively. The 12-month incidence of primary patency for DES treatment (83.2% [337 of 405]) was significantly greater than for BMS (74.3% [165 of 222]; P<0.01). Incidence of primary sustained clinical improvement was greater among patients treated with the DES than among those who received a BMS (83.0% versus 76.6%; P=0.045). The health-related quality of life dimensions of mobility and pain/discomfort improved for the majority of patients in both groups (for 66.4% and 53.6% of DES-treated and for 64.2% and 58.1% of BMS-treated patients, respectively) but did not differ significantly. At 12 months, no statistical difference was observed in all-cause mortality between patients treated with the DES or BMS (2.7% [13 of 474] versus 1.1% [3 of 263]; relative risk, 2.4 [95% CI, 0.69-8.36]; P=0.15). CONCLUSIONS: By demonstrating superior 1-year primary patency, the results of the EMINENT randomized study support the benefit of using a polymer-based paclitaxel-eluting stent as a first-line stent-based intervention for patients with symptomatic peripheral artery disease attributable to femoropopliteal lesions. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02921230.

Functionalized europium-doped hollow mesoporous silica nanospheres as a cell imaging and drug delivery agents.

In an effort to enhance the antitumor efficacy of breast cancer treatment, the chemotherapeutic agent Paclitaxel (PTX) was encapsulated within hyaluronic acid (HA) modified hollow mesoporous silica (HMSNs). In vitro drug release assays showed that the resulting formulation, Eu-HMSNs-HA-PTX, exhibited enzyme-responsive drug release. In addition, cell cytotoxicity and hemolysis assays demonstrated the favorable biocompatibility of both Eu-HMSNs and Eu-HMSNs-HA. Notably, compared to Eu-HMSNs alone, Eu-HMSNs-HA showed enhanced accumulation within CD44-expressing cancer cells (MDA-MB-231). As anticipated, apoptosis experiments indicated that Eu-HMSNs-HA-PTX displayed significantly greater cytotoxicity toward MDA-MB-231 cells than non-targeted Eu-HMSNs-PTX and free PTX. In conclusion, Eu-HMSNs-HA-PTX demonstrated excellent anticancer effects and holds promise as a potent candidate for the efficient therapy of breast cancer.

Dual drug delivery system of RAPTA-C and paclitaxel based on fructose coated nanoparticles for metastatic cancer treatment.

Ruthenium complexes have been widely studied as potential alternatives to platinum-type anticancer drugs due to their unique medical properties such as high selectivity, strong ability to inhibit solid tumour metastasis. However, non-specific biodistribution, and weak lethality of ruthenium to cancer cells limit its use in medical application. Drug delivery systems offer the ability to integrate multiple drugs in one system, which is particularly important to enhance the chemotherapeutic efficacy and to potentially achieve a synergistic effect of both drugs. Here, we report a dual drug nanocarrier that is based on a self-assembled biodegradable block copolymer, where the ruthenium complex (RAPTA-C) is chemically attached to the polymer chain, while another drug, paclitaxel (PTX), is entrapped in the core of the micelle. The dual drug delivery system was studied via in vitro tests using MDA-MB-231 breast cancer cells and it was observed that RAPTA-C in combination with PTX significantly enhanced anti-tumour and anti-metastasis activity.

Intraplaque wiring enables drug-coated balloons to be utilized for percutaneous recanalization of chronically occluded coronary arteries.

OBJECTIVES: This study aimed to determine whether drug-coated balloon (DCB) angioplasty following intraplaque wiring and the use of modified balloons is safe and effective in the percutaneous treatment of coronary chronic total occlusions (CTOs). BACKGROUND: DCB is an alternative therapeutic option without the limitations of permanent vascular implants. However, its efficacy in CTOs has yet to be confirmed. The combination of modified balloons and DCB can be effectively applied when the intraplaque passage of the guidewire is achieved in CTOs. METHODS: Data from 124 consecutive CTO lesions (105 patients) treated at our hospital between February 2016 and December 2020 were screened for inclusion and retrospectively analyzed. Among the 118 lesions successfully recanalized, intraplaque wiring was achieved in 108, and 85 were treated by the DCB-only approach following cutting/scoring balloon dilatation. RESULTS: Follow-up data were available for 82 lesions (71 patients). The median occlusion length was 18.5 mm, and the J-CTO score was 1.7 ± 0.9. No in-hospital major adverse cardiac events occurred, including abrupt vessel closure. During the median 29-month follow-up period, target lesion revascularization was performed for 10 lesions. Follow-up coronary angiography (8.7 ± 3.9 months after the index procedure) was performed for 64 lesions, demonstrating late lumen loss of -0.15 mm (interquartile range -0.4 to 0.23 mm), binary restenosis (diameter stenosis ≥50%) in 12 lesions (18.8%), and late lumen enlargement in 37 (57.8%). CONCLUSION: The DCB-only approach following the use of modified balloons is a promising strategy for coronary CTOs when intraplaque wiring is achieved.

Synthesis and Characterization of Paclitaxel-Loaded PEGylated Liposomes by the Microfluidics Method.

For cancer therapy, paclitaxel (PX) possesses several limitations, including limited solubility and untargeted effects. Loading PX into nanoliposomes to enhance PX solubility and target their delivery as a drug delivery system has the potential to overcome these limitations. Over the other conventional method to prepare liposomes, a microfluidic system is used to formulate PX-loaded PEGylated liposomes. The impact of changing the flow rate ratio (FRR) between the aqueous and lipid phases on the particle size and polydispersity index (PDI) is investigated. Moreover, the effect of changing the polyethylene glycol (PEG) lipid ratio on the particle size, PDI, stability, encapsulation efficiency % (EE %), and release profile is studied. The physicochemical characteristics of the obtained formulation were analyzed by dynamic light scattering, FTIR spectroscopy, and AFM. This work aims to use microfluidic technology to produce PEGylated PX-loaded liposomes with a diameter of <200 nm, low PDI < 0.25 high homogeneity, and viable 28 day stability. The results show a significant impact of FRR and PEG lipid ratio on the empty liposomes' physicochemical characteristics. Among the prepared formulations, two formulations produce size-controlled, low PDI, and stable liposomes, which make them preferable for PX encapsulation. The average EE % was >90% for both formulations, and the variation in the PEG lipid ratio affected the EE % slightly; a high packing for PX was reported at different drug concentrations. A variation in the release profiles was notified for the different PEG lipid ratios.