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International Journal of Biological... Mar 2023Liposomes and nanofibers have been introduced as effective drug delivery systems of anticancer drugs. The performance of chitosan (core)/poly(ε-caprolactone)...
Liposomes and nanofibers have been introduced as effective drug delivery systems of anticancer drugs. The performance of chitosan (core)/poly(ε-caprolactone) (PCL)/paclitaxel simple nanofibers, chitosan/paclitaxel (core)/PCL/chitosan (shell) nanofibers and paclitaxel-loaded liposome-incorporated chitosan (core)/PCL-chitosan (shell) nanofibers was investigated for the controlled release of paclitaxel and the treatment of breast cancer. The synthesized formulations were characterized using polydispersity index, dynamic light scattering, zeta potential, scanning electron microscopy, transmission electron microscopy, and Fourier transform infrared analysis. The sustained release of paclitaxel from liposome-loaded nanofibers was achieved within 30 days. The release data was best described using Korsmeyer-Peppas pharmacokinetic model. The cell viabilities of synthesized nanofibrous samples were higher than 98 % ± 1 % toward L929 normal cells after 168 h. The maximum cytotoxicity against MCF-7 breast cancer cells was 85 % ± 2.5 % using liposome-loaded core-shell nanofibers. The in vivo results indicated the reduction of tumor weight from 1.35 ± 0.15 g to 0.65 ± 0.05 g using liposome-loaded core-shell nanofibers and its increasing from 1.35 ± 0.15 g to 3.2 ± 0.2 g using pure core-shell nanofibers. The three-stage drug release behavior of paclitaxel-loaded liposome-incorporated core-shell nanofibers and the high in vivo tumor efficiency suggested the development of these formulations for cancer treatment in the future.
Topics: Humans; Female; Paclitaxel; Breast Neoplasms; Liposomes; Chitosan; Nanofibers; Polyesters
PubMed: 36706885
DOI: 10.1016/j.ijbiomac.2023.123380 -
International Journal of Pharmaceutics Mar 2020Bacterial therapy is emerging for the treatment of cancers though some scientific and clinical problems have not been addressed. Here, a live drug-loaded carrier,...
Bacterial therapy is emerging for the treatment of cancers though some scientific and clinical problems have not been addressed. Here, a live drug-loaded carrier, paclitaxel-in-liposome-in-bacteria (LPB), was prepared for inhalation treatment of primary lung cancer, where liposomal paclitaxel (LP) was highly effectively internalized into bacteria (E. coli or L. casei) to get LP-in-E. coli (LPE) or LP-in-L. casei (LPL) by electroporation that had no influence on the growth of these bacteria. Bacteria, LP, the simple mixture of LP and bacteria, and LPB remarkably inhibited the proliferation of A549 lung cancer cells, where LPE was the strongest one. Drug-loaded bacteria delivered the cargos into the cells more quickly than the mixture of drugs and bacteria and the cargos alone. LPE also showed the highest anticancer effect on the rat primary lung cancer among them with the downregulation of VEGF and HIF-1α and the improvement of cancer cell apoptosis after intratracheal administration. Moreover, the bacterial formulations significantly enhanced the expressions of immune markers (TNF-α, IL-4, and IFN-γ) and immune cells (leukocytes and neutrophils). LPB showed much higher bacterial distribution in the lung than other organs after intratracheal administration. LPB is a promising medicine for inhalation treatment of primary lung cancer.
Topics: A549 Cells; Administration, Inhalation; Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Biomarkers; Cell Line, Tumor; Cell Proliferation; Escherichia coli; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Leukocytes; Liposomes; Lung; Lung Neoplasms; Neutrophils; Paclitaxel; Rats; Vascular Endothelial Growth Factor A
PubMed: 32105724
DOI: 10.1016/j.ijpharm.2020.119177 -
Cancer Radiotherapie : Journal de La... Jul 2021The aim of this study was to evaluate the efficacy of liposome-paclitaxel and carboplatin combination chemoradiotherapy for patients with locally advanced esophageal...
PURPOSE
The aim of this study was to evaluate the efficacy of liposome-paclitaxel and carboplatin combination chemoradiotherapy for patients with locally advanced esophageal squamous cell carcinoma (ESCC).
PATIENTS AND METHODS
Seventy-nine consecutive patients treated with liposome-paclitaxel based concurrent chemoradiotherapy between January 2015 and December 2019 at Cancer hospital of the University of Chinese Academy of Sciences (Zhejiang cancer hospital) were enrolled in this study. The overall response, toxicities, progression-free survival and overall survival were analyzed with SPSS software.
RESULTS
A total of 302 cycles of weekly chemotherapy were delivered, with a median 4 courses. After concurrent chemoradiotherapy (CCRT), the efficacy was classified as CR in 4 cases (5.1%), PR in 22 cases (28.2%) and SD in 51 cases (65.4%). The median PFS and OS time were 18.2 months and 23.4 months. The 3-year PFS and OS rates were 45.1% and 43.6%, respectively.
CONCLUSIONS
Liposome-paclitaxel and carboplatin concurrent with radiotherapy is a safe and effective modality for locally advanced ESCC. Further clinical investigation are warranted to evaluate the efficacy of this regimen.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Chemoradiotherapy; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Female; Humans; Liposomes; Male; Middle Aged; Paclitaxel; Progression-Free Survival; Radiotherapy, Intensity-Modulated
PubMed: 33958272
DOI: 10.1016/j.canrad.2021.01.008 -
Zhonghua Nan Ke Xue = National Journal... Sep 2020To investigate the effect and safety of the 3-week paclitaxel liposome protocol in the treatment of castration-resistant prostate cancer (CRPC).
OBJECTIVE
To investigate the effect and safety of the 3-week paclitaxel liposome protocol in the treatment of castration-resistant prostate cancer (CRPC).
METHODS
This retrospective study included 40 cases of CRPC treated by the 3-week paclitaxel liposome protocol from February 2014 to February 2019, which involved intravenous injection of 10 mg dexamethasone in 100 ml normal saline on the first day and that of metoclopramide and panxi tora azole on the second day, followed by about 3 hours of intravenous drip of paclitaxel liposome at 135 mg/m2 for a course of 3 weeks. During the follow-up period, the patients received detection of the serum PSA level before treatment and chest x-ray and whole-body bone scan every six months. After two courses of treatment, the patients were observed for the changes in the serum PSA level, relief of bone pain, quality of survival, overall survival rate, overall survival time and toxic reactions. The protocol was continued unless the patient underwent progression, refused for unacceptable toxicity, or died.
RESULTS
The patients were aged 59 to 79 (mean 68.80±5.67) years old, with the serum PSA level of (28.05 ± 3.22) μg/L at the baseline and (4.12 ± 0.23) μg/L after treatment. Thirty-eight of the patients were followed up for 3 to 33 (mean 12.2) months. PSA-based evaluation showed therapeutic effectiveness in 14 cases (35%), stable condition in 21 (52.5 %) and progression in 5 (12.5 %). Of the 18 patients with bone metastasis and pain, 16 (88.9 %) experienced relief of the symptoms and reduced the use of painkillers, with the bone pain scores of 5.20 ± 1.22 vs 2.79 ± 0.57 before and after treatment. By the end of the follow-up, the overall survival rate was 55.0% (22/40) and the median survival time was 17 months (95% CI: 13.4-24.6). During the treatment, no obvious adverse reactions were observed except for anemia in 1 case and hair loss in another.
CONCLUSIONS
For the treatment of CRPC in China, the 3-week paclitaxel liposome protocol has the advantages of desirable safety, low toxicity, acceptable drug tolerance and improved quality of survival, but its curative effect needs to be verified with more randomized clinical trials with larger samples and longer follow-ups.
Topics: Aged; Bone Neoplasms; China; Humans; Liposomes; Male; Middle Aged; Paclitaxel; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Retrospective Studies; Survival Rate; Treatment Outcome
PubMed: 33377700
DOI: No ID Found -
Cancer Treatment Reviews May 2021Pancreatic ductal adenocarcinoma (PDAC) is an aggressive form of cancer with a dismal prognosis. The lack of symptoms in the early phase of the disease makes early... (Review)
Review
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive form of cancer with a dismal prognosis. The lack of symptoms in the early phase of the disease makes early diagnosis challenging, and about 80-85% of the patients are diagnosed only after the disease is locally advanced or metastatic. The current front-line treatment landscape in local stages comprises surgical resection and adjuvant chemotherapy. In Switzerland, although both FOLFIRINOX and gemcitabine plus nab-paclitaxel regimens are feasible and comparable in the first-line setting, FOLFIRINOX is preferred in the treatment of fit (Eastern Cooperative Oncology Group [ECOG] performance status [PS]: 0-1), young (<65 years old) patients with few comorbidities and normal liver function, while gemcitabine plus nab-paclitaxel is used to treat less fit (ECOG PS: 1-2) and more vulnerable patients. In the second-line setting of advanced PDAC, there is currently only one approved regimen, based on the phase III NAPOLI-1 trial. Furthermore, the use of liposomal-irinotecan in the second line is supported by real-world data. Beyond the standard of care, various alternative treatment modalities are being explored in clinical studies. Immunotherapy has demonstrated only limited benefits until now, and only in cases of high microsatellite instability (MSI-H). However, data on the benefit of poly (ADP-ribose) polymerase (PARP) inhibition as maintenance therapy in patients with germline BRCA-mutated tumors might signal of an advance in targeted therapy. Currently, there is a lack of molecular and genetic biomarkers for optimal stratification of patients and in guiding treatment decisions. Thus, identification of predictive and prognostic biomarkers and evaluating novel treatment strategies are equally relevant for improving the prognosis of metastatic pancreatic cancer patients.
Topics: Albumins; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; Clinical Trials, Phase III as Topic; Deoxycytidine; Fluorouracil; Humans; Irinotecan; Leucovorin; Liposomes; Neoplasm Metastasis; Oxaliplatin; Paclitaxel; Pancreatic Neoplasms; Randomized Controlled Trials as Topic; Gemcitabine
PubMed: 33812339
DOI: 10.1016/j.ctrv.2021.102180 -
Pharmaceutical Research Mar 2015Albumin nanoparticles have been explored as a promising delivery system for various therapeutic agents. One limitation of such formulations is their poor colloidal... (Comparative Study)
Comparative Study
PURPOSE
Albumin nanoparticles have been explored as a promising delivery system for various therapeutic agents. One limitation of such formulations is their poor colloidal stability in vivo. Present study aimed at enhancing the chemotherapeutic potential of paclitaxel by improving the colloidal stability and pharmacokinetic properties of albumin-paclitaxel nanoparticles (APNs) such as Abraxane®.
METHODS
This was accomplished by encapsulating the preformed APNs into PEGylated liposomal bilayer by thin-film hydration/extrusion technique.
RESULTS
The resulting liposome-encapsulated albumin-paclitaxel hybrid nanoparticles (L-APNs) were nanosized (~200 nm) with uniform spherical dimensions. The successful incorporation of albumin-paclitaxel nanoparticle (NP) in liposome was confirmed by size exclusion chromatography analysis. Such hybrid NP showed an excellent colloidal stability even at 100-fold dilutions, overcoming the critical drawback associated with simple albumin-paclitaxel NP system. L-APNs further showed higher cytotoxic activity towards B16F10 and MCF-7 cells than APN; this effect was characterized by arrest at the G2/M phase and a higher prevalence of apoptotic subG1 cells. Finally, pharmacokinetic and biodistribution studies in tumor mice demonstrated that L-APNs showed a significantly enhanced plasma half-life, and preferential accumulation in the tumor.
CONCLUSIONS
Taken together, the data indicate that L-APNs can be promising therapeutic vehicles for enhanced delivery of PTX to tumor sites.
Topics: Albumin-Bound Paclitaxel; Albumins; Animals; Antineoplastic Agents, Phytogenic; Breast Neoplasms; Cell Survival; Chemistry, Pharmaceutical; Drug Stability; Female; G2 Phase Cell Cycle Checkpoints; Half-Life; Humans; Injections, Intravenous; Lipids; Liposomes; MCF-7 Cells; Male; Melanoma, Experimental; Mice; Mice, Inbred BALB C; Nanomedicine; Nanoparticles; Paclitaxel; Particle Size; Polyethylene Glycols; Solubility; Technology, Pharmaceutical; Tissue Distribution
PubMed: 25213777
DOI: 10.1007/s11095-014-1512-2 -
Cancer Communications (London, England) Jan 2022Lipusu is the first commercialized liposomal formulation of paclitaxel and has demonstrated promising efficacy against locally advanced lung squamous cell carcinoma... (Randomized Controlled Trial)
Randomized Controlled Trial
Paclitaxel liposome for injection (Lipusu) plus cisplatin versus gemcitabine plus cisplatin in the first-line treatment of locally advanced or metastatic lung squamous cell carcinoma: A multicenter, randomized, open-label, parallel controlled clinical study.
BACKGROUND
Lipusu is the first commercialized liposomal formulation of paclitaxel and has demonstrated promising efficacy against locally advanced lung squamous cell carcinoma (LSCC) in a small-scale study. Here, we conducted a multicenter, randomized, phase 3 study to compare the efficacy and safety of cisplatin plus Lipusu (LP) versus cisplatin plus gemcitabine (GP) as first-line treatment in locally advanced or metastatic LSCC.
METHODS
Patients enrolled were aged between 18 to 75 years, had locally advanced (clinical stage IIIB, ineligible for concurrent chemoradiation or surgery) or metastatic (Stage IV) LSCC, had no previous systemic chemotherapy and at least one measurable lesion as per the Response Evaluation Criteria in Solid Tumors (version 1.1) before administration of the trial drug. The primary endpoint was progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety profiles. To explore the possible predictive value of plasma cytokines for LP treatment, plasma samples were collected from the LP group at baseline and first efficacy evaluation time and were then subjected to analysis by 45-Plex ProcartaPlex Panel 1 to detect the presence of 45 cytokines using the Luminex xMAP technology. The correlation between treatment outcomes and dynamic changes in the levels of cytokines were evaluated in preliminary analyses.
RESULTS
The median duration of follow-up was 15.4 months. 237 patients in the LP group and 253 patients in the GP group were included in the per protocol set (PPS). In the PPS, the median PFS was 5.2 months versus 5.5 months in the LP and GP group (hazard ratio [HR]: 1.03, P = 0.742) respectively. The median OS was 14.6 months versus 12.5 months in the LP and GP group (HR: 0.83, P = 0.215). The ORR (41.8% versus 45.9%, P = 0.412) and DCR (90.3% versus 88.1%, P = 0.443) were also similar between the LP and GP group. A significantly lower proportion of patients in the LP group experienced adverse events (AEs) leading to treatment interruptions (10.9% versus 26.4%, P < 0.001) or treatment termination (14.3% versus 23.1%, P = 0.011). The analysis of cytokine levels in the LP group showed that low baseline levels of 27 cytokines were associated with an increased ORR, and 15 cytokines were associated with improved PFS, with 14 cytokines, including TNF-α, IFN-γ, IL-6, and IL-8, demonstrating an overlapping trend.
CONCLUSION
The LP regimen demonstrated similar PFS, OS, ORR and DCR as the GP regimen for patients with locally advanced or metastatic LSCC but had more favorable toxicity profiles. The study also identified a spectrum of different cytokines that could be potentially associated with the clinical benefit in patients who received the LP regimen.
Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Deoxycytidine; Humans; Liposomes; Lung; Lung Neoplasms; Middle Aged; Paclitaxel; Young Adult; Gemcitabine
PubMed: 34699693
DOI: 10.1002/cac2.12225 -
Genetics and Molecular Research : GMR Apr 2016We sought to determine the efficacy of atomized paclitaxel liposome inhalation treatment of pulmonary fibrosis in a bleomycin-induced rat model. Forty male...
We sought to determine the efficacy of atomized paclitaxel liposome inhalation treatment of pulmonary fibrosis in a bleomycin-induced rat model. Forty male Sprague-Dawley rats were randomly divided into four groups: healthy control, pulmonary fibrosis without treatment, paclitaxel liposome inhalation-treated, and intravenous paclitaxel liposome-treated. Fibrosis was induced by bleomycin injection. A total of 20 mg/kg paclitaxel liposome was administered by inhalation every other day for a total of 10 doses. The intravenous group received 5 mg/kg paclitaxel liposome on days 1, 7, 14, and 21. We observed the general condition, weight change, survival index, and pathological changes in the lung tissue of the rats. Quantitative analysis of collagen types I and III and transforming growth factor (TGF)-β1 expression in the lungs was also performed. The paclitaxel liposome inhalation and intravenous delivery methods improved survival index and pulmonary fibrosis Ashcroft score, and decreased the thickness of the alveolar interval. No obvious difference was found between the two groups. Compared with the untreated group, paclitaxel liposome inhalation and intravenous injection significantly reduced the levels of collagen types I and III and TGF-β1 expression equally. In conclusion, atomized paclitaxel liposome inhalation protects against severe pulmonary fibrosis in a bleomycin-induced rat model. This delivery method has less systemic side effects and increased safety over intravenous injection.
Topics: Administration, Inhalation; Animals; Bleomycin; Collagen Type I; Collagen Type III; Injections, Intravenous; Liposomes; Male; Paclitaxel; Pulmonary Fibrosis; Rats; Rats, Sprague-Dawley; Transforming Growth Factor beta1
PubMed: 27173212
DOI: 10.4238/gmr.15027309 -
Journal of Advanced Research Jul 2023Inherent or acquired resistance to paclitaxel (PTX) is a pivotal challenge for chemotherapy treatment of multidrug-resistant (MDR) breast cancer. Although various...
INTRODUCTION
Inherent or acquired resistance to paclitaxel (PTX) is a pivotal challenge for chemotherapy treatment of multidrug-resistant (MDR) breast cancer. Although various targeted drug-delivery systems, including nanoparticles and liposomes, are effective for MDR cancer treatment, their efficacy is restricted by immunosuppressive tumor microenvironment (TME).
METHODS
Ginsenosides Rg3 was used to formulate unique Rg3-based liposomes loaded with PTX to establish Rg3-PTX-LPs, which were prepared by the thin-film hydration method. The stability of the Rg3-PTX-LPs was evaluated by particle size analysis through dynamic light scattering. The active targeting effect of Rg3-based liposomes was examined in an MCF-7/T xenograft model by an in a vivo imaging system. To evaluate the antitumor activity and mechanism of Rg3-PTX-LP, MTT, apoptosis assays, TAM regulation, and TME remodeling were performed in MCF-7/T cells in vitro and in vivo.
RESULTS
Rg3-PTX-LPs could specifically distribute to MCF7/T cancer cells and TME simultaneously, mainly through the recognition of GLUT-1. The drug resistance reversing capability and in vivo antitumor effect of Rg3-PTX-LPs were significantly improved compared with conventional cholesterol liposomes. The TME remodeling mechanisms of Rg3-PTX-LPs included inhibiting IL-6/STAT3/p-STAT3 pathway activation to repolarize protumor M2 macrophages to antitumor M1 phenotype, suppressing myeloid-derived suppressor cells (MDSCs), decreasing tumor-associated fibroblasts (TAFs) and collagen fibers in TME, and promoting apoptosis of tumor cells. Hence, through the dual effects of targeting tumor cells and TME remodeling, Rg3-PTX-LPs achieved a high tumor inhibition rate of 90.3%.
CONCLUSION
Our multifunctional Rg3-based liposome developed in the present study offered a promising strategy for rescuing the drug resistance tumor treatment.
Topics: Humans; Paclitaxel; Liposomes; Ginsenosides; Tumor Microenvironment; Lipopolysaccharides; Neoplasms
PubMed: 36167294
DOI: 10.1016/j.jare.2022.09.007 -
Cancer Medicine Mar 2023This single-center retrospective clinical study aimed to evaluate the efficacy and feasibility of chemoradiotherapy with paclitaxel liposome plus cisplatin for locally...
PURPOSE
This single-center retrospective clinical study aimed to evaluate the efficacy and feasibility of chemoradiotherapy with paclitaxel liposome plus cisplatin for locally advanced esophageal squamous cell carcinoma (ESCC).
METHODS
Patients with locally advanced ESCC treated with paclitaxel-liposome-based chemoradiotherapy between 2016 and 2019 were retrospectively analyzed. Overall survival (OS) and progression-free survival (PFS) were evaluated using Kaplan-Meier analysis.
RESULTS
Thirty-nine patients with locally advanced ESCC were included in this study. The median follow-up time was 31.5 months. The median OS time was 38.3 (95% confidence interval [CI]: 32.1-45.1) months, and the 1-, 2-, and 3-year OS rates were 84.6%, 64.1%, and 56.2%, respectively. The median PFS time was 32.1 (95% CI: 25.4-39.0) months, and the 1-, 2-, and 3-year PFS rates were 71.8%, 43.6%, and 43.6%, respectively. The most common Grade IV toxicity was neutropenia (30.8%) followed by lymphopenia (20.5%). There were no cases of Grade III/IV radiation pneumonia, and four patients (10.3%) had Grade III/IV esophagitis.
CONCLUSION
Chemoradiotherapy using paclitaxel liposome and cisplatin is a well-tolerated and effective treatment regimen for locally advanced ESCC.
Topics: Humans; Esophageal Squamous Cell Carcinoma; Cisplatin; Esophageal Neoplasms; Retrospective Studies; Liposomes; Carcinoma, Squamous Cell; Disease-Free Survival; Paclitaxel; Chemoradiotherapy; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37012831
DOI: 10.1002/cam4.5416