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Synthesis and Characterization of Paclitaxel-Loaded PEGylated Liposomes by the Microfluidics Method.Molecular Pharmaceutics Dec 2023For cancer therapy, paclitaxel (PX) possesses several limitations, including limited solubility and untargeted effects. Loading PX into nanoliposomes to enhance PX...
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.
Topics: Paclitaxel; Liposomes; Microfluidics; Polyethylene Glycols; Lipids; Particle Size
PubMed: 37931072
DOI: 10.1021/acs.molpharmaceut.3c00596 -
Southern Medical Journal Nov 2020Preoperative chemotherapy produces tumor shrinkage in most patients with locally advanced breast cancer, including some pathological complete responses (pCRs). We...
OBJECTIVES
Preoperative chemotherapy produces tumor shrinkage in most patients with locally advanced breast cancer, including some pathological complete responses (pCRs). We attempted this using a much less toxic sequential regimen, given with concurrent bevacizumab.
METHODS
Patients with locally advanced breast cancer received 3 intravenous doses each of preoperative sequential liposome encapsulated doxorubicin 25 mg/m, paclitaxel 175 mg/m, and cyclophosphamide 600 mg/m, with concurrent bevacizumab every 2 weeks without growth factor support.
RESULTS
Between March 2008 and December 2009, 32 patients received treatment. There was no cardiotoxicity, and other toxicity was mild (no grade 4 or 5 toxicity). No long-term toxicity, including cardiotoxicity, has been observed. Every patient had ≥30% reduction in tumor size; 9 of 31 patients who completed chemotherapy had pCR at operation. Seven years later, 22 of 32 patients remain free of recurrence and 27 of 32 are alive.
CONCLUSIONS
The preoperative chemotherapy used appears to be comparably effective, but much less toxic than that used in most conventional regimens and should be studied further. Concurrent treatment with bevacizumab (reported separately) did not provide any additional benefit.
Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Breast Neoplasms; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Female; Humans; Middle Aged; Paclitaxel; Pilot Projects
PubMed: 33140109
DOI: 10.14423/SMJ.0000000000001169 -
Gynecologic Oncology Aug 2022In patients with recurrent/advanced endometrial cancer who have progressed after first-line treatment, there are a lack of real-world data on treatment patterns,...
OBJECTIVES
In patients with recurrent/advanced endometrial cancer who have progressed after first-line treatment, there are a lack of real-world data on treatment patterns, characteristics, and survival outcomes. A novel study was conducted to determine real-world treatment patterns and outcomes in England.
METHODS
This non-interventional study used routine, administrative health data from the National Cancer Registration and Analysis Service in England to identify patients diagnosed with recurrent/advanced endometrial cancer between 1 January 2013 and 31 December 2018, inclusive. A cohort of patients who progressed to second-line treatment were identified as the 'immune checkpoint inhibitor-eligible second-line' cohort. The co-primary objectives were to summarise baseline demographics, disease characteristics, treatments received, and depict overall survival and time-to-next-treatment (a proxy for progression-free survival) from the start of second-line therapy using Kaplan-Meier methodology.
RESULTS
Overall, 12,058 patients were diagnosed with recurrent/advanced endometrial cancer; 999 patients were included in the immune checkpoint inhibitor-eligible second-line cohort and 77.9% (778 of 999) had advanced disease (Stage III/IV). The most common treatments received at second-line were carboplatin plus paclitaxel (27.9%), carboplatin plus liposomal doxorubicin (14.1%), liposomal doxorubicin monotherapy (13.0%), and paclitaxel monotherapy (11.6%). From initiation of second-line therapy, median (95% confidence interval) overall survival was 10.3 months (9.2-11.1), and median time-to-next-treatment was 7.7 months (7.1-8.2).
CONCLUSIONS
Treatments received in the relapsed setting were variable and survival outcomes poor at second-line, highlighting the need for standard of care guidance and innovative therapies to improve patient outcomes in England and in countries with similar treatment patterns.
FUNDING
GSK.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Endometrial Neoplasms; Female; Humans; Immune Checkpoint Inhibitors; Neoplasm Recurrence, Local; Paclitaxel; Retrospective Studies
PubMed: 35752507
DOI: 10.1016/j.ygyno.2022.06.011 -
The Lancet. Global Health Aug 2022The most effective treatment for advanced AIDS-associated Kaposi sarcoma is paclitaxel or pegylated liposomal doxorubicin (PLD); neither is routinely used in sub-Saharan...
BACKGROUND
The most effective treatment for advanced AIDS-associated Kaposi sarcoma is paclitaxel or pegylated liposomal doxorubicin (PLD); neither is routinely used in sub-Saharan Africa due to limited availability and high cost. We examined the clinical impact, costs, and cost-effectiveness of paclitaxel or PLD in Kenya, compared with etoposide or bleomycin-vincristine.
METHODS
In this study, we use the Cost-Effectiveness of Preventing AIDS Complications (CEPAC)-International Model to project clinical outcomes and costs among people living with HIV and advanced Kaposi sarcoma on antiretroviral therapy. We compared four different treatment strategies: etoposide, bleomycin-vincristine, paclitaxel, or PLD. We derived cohort characteristics and costs from the Kenyan Academic Model for Providing Access to Healthcare network, and adverse events, efficacy, and mortality from clinical trials. We projected model outcomes over a lifetime and included life expectancy, per-person lifetime costs, and incremental cost-effectiveness ratios (ICERs). We conducted budget impact analysis for 5-year total costs and did deterministic and probabilistic sensitivity analyses to evaluate the effect of uncertainty in input parameters.
FINDINGS
We found that paclitaxel would be more effective than bleomycin-vincristine and would increase life expectancy by 4·2 years per person. PLD would further increase life expectancy by 0·6 years per person. Paclitaxel would be the most cost-effective strategy (ICER US$380 per year-of-life-saved compared with bleomycin-vincristine) and would remain cost-effective across a range of scenarios. PLD would be cost-effective compared with paclitaxel if its price were reduced to $100 per cycle (base case $180 per cycle). Implementing paclitaxel instead of bleomycin-vincristine would save approximately 6400 life-years and would increase the overall 5-year Kenyan health-care costs by $3·7 million; increased costs would be primarily related to ongoing HIV care given improved survival.
INTERPRETATION
Paclitaxel would substantially increase life expectancy and be cost-effective compared with bleomycin-vincristine for advanced AIDS-associated Kaposi sarcoma in Kenya and should be the standard of care. PLD would further improve survival and be cost-effective with a 44% price reduction.
FUNDING
US National Institutes of Health and Massachusetts General Hospital.
TRANSLATION
For the Swahili translation of the abstract see Supplementary Materials section.
Topics: Acquired Immunodeficiency Syndrome; Bleomycin; Cost-Benefit Analysis; Etoposide; HIV Infections; Humans; Kenya; Paclitaxel; Sarcoma, Kaposi; Vincristine
PubMed: 35839816
DOI: 10.1016/S2214-109X(22)00242-X -
International Journal of Molecular... Sep 2018Tumours are complex systems of genetically diverse malignant cells that proliferate in the presence of a heterogeneous microenvironment consisting of host derived... (Review)
Review
Tumours are complex systems of genetically diverse malignant cells that proliferate in the presence of a heterogeneous microenvironment consisting of host derived microvasculature, stromal, and immune cells. The components of the tumour microenvironment (TME) communicate with each other and with cancer cells, to regulate cellular processes that can inhibit, as well as enhance, tumour growth. Therapeutic strategies have been developed to modulate the TME and cancer-associated immune response. However, modulating compounds are often insoluble (aqueous solubility of less than 1 mg/mL) and have suboptimal pharmacokinetics that prevent therapeutically relevant drug concentrations from reaching the appropriate sites within the tumour. Nanomedicines and, in particular, liposomal formulations of relevant drug candidates, define clinically meaningful drug delivery systems that have the potential to ensure that the right drug candidate is delivered to the right area within tumours at the right time. Following encapsulation in liposomes, drug candidates often display extended plasma half-lives, higher plasma concentrations and may accumulate directly in the tumour tissue. Liposomes can normalise the tumour blood vessel structure and enhance the immunogenicity of tumour cell death; relatively unrecognised impacts associated with using liposomal formulations. This review describes liposomal formulations that affect components of the TME. A focus is placed on formulations which are approved for use in the clinic. The concept of tumour immunogenicity, and how liposomes may enhance radiation and chemotherapy-induced immunogenic cell death (ICD), is discussed. Liposomes are currently an indispensable tool in the treatment of cancer, and their contribution to cancer therapy may gain even further importance by incorporating modulators of the TME and the cancer-associated immune response.
Topics: Animals; Antineoplastic Agents; Cell Death; Drug Delivery Systems; Humans; Liposomes; Neoplasms; T-Lymphocytes; Tumor Microenvironment
PubMed: 30261606
DOI: 10.3390/ijms19102922 -
The Journal of International Medical... Sep 2023To compare the efficacy of paclitaxel liposomes combined with carboplatin and paclitaxel combined with carboplatin in the treatment of advanced ovarian cancer and assess... (Observational Study)
Observational Study
OBJECTIVE
To compare the efficacy of paclitaxel liposomes combined with carboplatin and paclitaxel combined with carboplatin in the treatment of advanced ovarian cancer and assess their effects on serum human epididymis protein 4 (HE4), CA125, CA199, matrix metalloproteinase-2 (MMP2), MMP-7, and MMP-9 levels.
METHODS
In this observational study, 102 patients with advanced ovarian cancer were assigned to receive paclitaxel liposomes combined with carboplatin (Group A) or paclitaxel combined with carboplatin (Group B). Clinical efficacy; serum HE4, CA125, CA199, MMP-2, MMP-7, and MMP-9 levels; and the occurrence of adverse reactions were compared between the groups.
RESULTS
The overall response rate was significantly higher in Group A than in Group B. After chemotherapy, serum HE4, CA125, CA199, MMP-2, MMP-7, and MMP-9 levels were lower in Group A than in Group B. The incidence of myalgia, dyspnea, nausea and vomiting, facial flushing, peripheral neuropathy, and skin rash was lower in Group A than in Group B.
CONCLUSION
Paclitaxel liposomes combined with carboplatin displayed better efficacy in the treatment of advanced ovarian cancer than paclitaxel combined with carboplatin, which might be attributable to reductions in serum marker levels and the occurrence of adverse events.
Topics: Female; Humans; Matrix Metalloproteinase 2; Carboplatin; Liposomes; Matrix Metalloproteinase 7; Matrix Metalloproteinase 9; Paclitaxel; CA-125 Antigen; Carcinoma, Ovarian Epithelial; Ovarian Neoplasms
PubMed: 37756606
DOI: 10.1177/03000605231200267 -
International Journal of Nanomedicine 2024Most solid tumors are not diagnosed and treated until the advanced stage, in which tumors have shaped mature self-protective power, leading to off-target drugs and...
BACKGROUND
Most solid tumors are not diagnosed and treated until the advanced stage, in which tumors have shaped mature self-protective power, leading to off-target drugs and nanomedicines. In the present studies, we established a more realistic large tumor model to test the antitumor activity of a multifunctional ginsenoside Rh2-based liposome system (Rh2-lipo) on advanced breast cancer.
METHODS
Both cholesterol and PEG were substituted by Rh2 to prepare the Rh2-lipo using ethanol-water system and characterized. The effects of Rh2-lipo on cell uptake, penetration of the tumor spheroid, cytotoxicity assay was investigated with 4T1 breast cancer cells and L929 fibroblast cells. The 4T1 orthotopic-bearing large tumor model was established to study the targeting effect of Rh2-lipo and inhibitory effect of paclitaxel loaded Rh2-lipo (PTX-Rh2-lipo) on advanced breast tumors.
RESULTS
Rh2-lipo exhibit many advantages that address the limitations of current liposome formulations against large tumors, such as enhanced uptake in TAFs and tumor cells, high targeting and penetration capacity, cytotoxicity against TAFs, normalization of the vessel network, and depletion of stromal collagen. In in vivo study, PTX-Rh2-lipo effectively inhibiting the growth of advanced breast tumors and outperformed most reported PTX formulations, including Lipusu and Abraxane.
CONCLUSION
Rh2-lipo have improved drug delivery efficiency and antitumor efficacy in advanced breast cancer, which offers a novel promising platform for advanced tumor therapy.
Topics: Humans; Female; Liposomes; Breast Neoplasms; Drug Delivery Systems; Paclitaxel; Cell Line, Tumor; Ginsenosides
PubMed: 38525007
DOI: 10.2147/IJN.S437733 -
International Journal of Nanomedicine 2017Breast cancer is the most common malignant disease in women worldwide, but the current drug therapy is far from optimal as indicated by the high death rate of breast... (Review)
Review
Breast cancer is the most common malignant disease in women worldwide, but the current drug therapy is far from optimal as indicated by the high death rate of breast cancer patients. Nanomedicine is a promising alternative for breast cancer treatment. Nanomedicine products such as Doxil and Abraxane have already been extensively used for breast cancer adjuvant therapy with favorable clinical outcomes. However, these products were originally designed for generic anticancer purpose and not specifically for breast cancer treatment. With better understanding of the molecular biology of breast cancer, a number of novel promising nanotherapeutic strategies and devices have been developed in recent years. In this review, we will first give an overview of the current breast cancer treatment and the updated status of nanomedicine use in clinical setting, then discuss the latest important trends in designing breast cancer nanomedicine, including passive and active cancer cell targeting, breast cancer stem cell targeting, tumor microenvironment-based nanotherapy and combination nanotherapy of drug-resistant breast cancer. Researchers may get insight from these strategies to design and develop nanomedicine that is more tailored for breast cancer to achieve further improvements in cancer specificity, antitumorigenic effect, antimetastasis effect and drug resistance reversal effect.
Topics: Albumin-Bound Paclitaxel; Antineoplastic Agents; Breast Neoplasms; Doxorubicin; Drug Delivery Systems; Female; Humans; Molecular Targeted Therapy; Nanomedicine; Neoplastic Stem Cells; Polyethylene Glycols; Receptor, ErbB-2; Tumor Microenvironment
PubMed: 28860754
DOI: 10.2147/IJN.S123437 -
International Journal of Molecular... Mar 2021Biocompatible nanoparticles (NPs) containing polymers, lipids (liposomes and micelles), dendrimers, ferritin, carbon nanotubes, quantum dots, ceramic, magnetic... (Review)
Review
Biocompatible nanoparticles (NPs) containing polymers, lipids (liposomes and micelles), dendrimers, ferritin, carbon nanotubes, quantum dots, ceramic, magnetic materials, and gold/silver have contributed to imaging diagnosis and targeted cancer therapy. However, only some NP drugs, including Doxil (liposome-encapsulated doxorubicin), Abraxane (albumin-bound paclitaxel), and Oncaspar (PEG-Asparaginase), have emerged on the pharmaceutical market to date. By contrast, several phytochemicals that were found to be effective in cultured cancer cells and animal studies have not shown significant efficacy in humans due to poor bioavailability and absorption, rapid clearance, resistance, and toxicity. Research to overcome these drawbacks by using phytochemical NPs remains in the early stages of clinical translation. Thus, in the current review, we discuss the progress in nanotechnology, research milestones, the molecular mechanisms of phytochemicals encapsulated in NPs, and clinical implications. Several challenges that must be overcome and future research perspectives are also described.
Topics: Animals; Antineoplastic Agents, Phytogenic; Drug Delivery Systems; Humans; Mononuclear Phagocyte System; Nanoparticles; Nanotechnology; Nanotubes, Carbon; Neoplasms; Phytochemicals; Quantum Dots
PubMed: 33808235
DOI: 10.3390/ijms22073571 -
3 Biotech Mar 2022Breast cancer is a heterogeneous disease with different intrinsic subtypes. The conventional treatment of surgical resection, chemotherapy, immunotherapy and... (Review)
Review
Breast cancer is a heterogeneous disease with different intrinsic subtypes. The conventional treatment of surgical resection, chemotherapy, immunotherapy and radiotherapy has not shown significant improvement in the survival rate of breast cancer patients. The therapeutics used cause bystander toxicities deteriorating healthy tissues. The breakthroughs of nanotechnology have been a promising feat in selective targeting of tumor site thus increasing the therapeutic gain. By the application of nanoenabled carriers, nanomedicines ensure targeted delivery, stability, enhanced cellular uptake, biocompatibility and higher apoptotic efficacy. The present review focuses on breakthrough of nanoscale intervention in targeted drug delivery as novel class of therapeutics. Nanoenabled carriers like polymeric and metallic nanoparticles, dendrimers, quantum dots, liposomes, solid lipid nanoparticles, carbon nanotubes, drug-antibody conjugates and exosomes revolutionized the targeted therapeutic delivery approach. These nanoassemblies have shown additional effect of improving the solubility of drugs such as paclitaxel, reducing the dose and toxicity. The present review provides an insight on the different drug conjugates employed/investigated to curb breast cancer using nanocarrier mediated targeted drug delivery. However, identification of appropriate biomarkers to target, clearer insight of the biological processes, batch uniformity, reproducibility, nanomaterial toxicity and stabilities are the hurdles faced by nanodrugs. The potential of nano-therapeutics delivery necessitates the agglomerated efforts of research community to bridge the route of nanodrugs for scale-up, commercialization and clinical applications.
PubMed: 35223356
DOI: 10.1007/s13205-022-03121-6