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Therapeutic Delivery Feb 2024This study aims to assess the efficacy of free and niosomes-loaded paclitaxel combined with the anti-diabetic drug metformin. Paclitaxel was successfully encapsulated...
This study aims to assess the efficacy of free and niosomes-loaded paclitaxel combined with the anti-diabetic drug metformin. Paclitaxel was successfully encapsulated in all niosome formulations, using microfluidic mixing, with a maximum encapsulation efficiency of 11.9%. The half maximal inhibitory concentration (IC) for free paclitaxel in T47D cells was significantly reduced from 0.2 to 0.048 mg/ml when combined with metformin 40 mg. The IC of paclitaxel was significantly reduced when loaded in niosomes to less than 0.06 mg/ml alone or with metformin. Paclitaxel combination (free or loaded into niosomes) with metformin significantly improved the anticancer efficacy of paclitaxel, which can serve as a method to reduce the paclitaxel dose and its associated side effects.
Topics: Paclitaxel; Liposomes; Metformin; Drug Compounding; Cell Line, Tumor
PubMed: 38214106
DOI: 10.4155/tde-2023-0089 -
Frontiers in Bioengineering and... 2023Nowadays, it is still quite difficult to combat glioblastoma, which is one of the most lethal cancers for human beings. Combinatory therapy, which could not only improve...
Light-activatable and hyperthermia-sensitive "all-in-one" theranostics: NIR-II fluorescence imaging and chemo-photothermal therapy of subcutaneous glioblastoma by temperature-sensitive liposome-containing AIEgens and paclitaxel.
Nowadays, it is still quite difficult to combat glioblastoma, which is one of the most lethal cancers for human beings. Combinatory therapy, which could not only improve therapeutic efficacy and overcome multiple drug resistance but also decrease the threshold therapeutic drug dosage and minimize side effects, would be an appealing candidate for glioblastoma treatment. Herein, we report fluorescence imaging in the second near-infrared window (NIR-II)-guided combinatory photothermal therapy (PTT) and chemotherapy of glioblastoma with a newly formulated nanomedicine termed . It is composed of temperature-sensitive liposome (TSL) carriers, NIR-II emissive and photothermal aggregation-induced emission (AIE) dyes, and chemotherapeutic paclitaxel (PTX) as well. shows spherical morphology with diameters of approximately 55 and 85 nm by transmission electron microscopy and laser light scattering, respectively, a zeta potential of -14.83 mV, good stability in both size and photoactivity, strong light absorption with a peak of approximately 770 nm, and bright emission from 900 nm to 1,200 nm. After excitation with an 808-nm laser with good spatiotemporal controllability, emits bright NIR-II fluorescence signals for tumor diagnosis , exhibits high photothermal conversion efficiency (68.8%), and triggers drug release of PTX under hypothermia, which assists in efficient tumor ablation and . This research demonstrates that "all-in-one" theranostics with NIR-II fluorescence imaging-guided combinatory PTT and chemotherapy is an efficient treatment paradigm for improving the prognosis of brain cancers.
PubMed: 38213575
DOI: 10.3389/fbioe.2023.1343694 -
Journal of Oncology Pharmacy Practice :... Mar 2024Paclitaxel is an effective chemotherapeutic agent against a variety of cancer types. However, the clinical utility of paclitaxel is restricted by its poor solubility in... (Review)
Review
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.
Topics: Humans; Micelles; Antineoplastic Agents, Phytogenic; Albumin-Bound Paclitaxel; Paclitaxel; Drug Delivery Systems; Polymers; Drug Carriers
PubMed: 38204196
DOI: 10.1177/10781552231208978 -
JAMA Network Open Jan 2024The NAPOLI 3 trial showed the superiority of fluorouracil, leucovorin, liposomal irinotecan, and oxaliplatin (NALIRIFOX) over the combination of gemcitabine and... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
The NAPOLI 3 trial showed the superiority of fluorouracil, leucovorin, liposomal irinotecan, and oxaliplatin (NALIRIFOX) over the combination of gemcitabine and nab-paclitaxel (GEM-NABP) as first-line treatment of metastatic pancreatic ductal adenocarcinoma (PDAC). Analyses comparing NALIRIFOX and GEM-NABP with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) have not yet been reported.
OBJECTIVE
To derive survival, response, and toxic effects data from phase 3 clinical trials and compare NALIRIFOX, FOLFIRINOX, and GEM-NABP.
DATA SOURCES
After a systematic search of PubMed, Scopus, Embase, and American Society of Clinical Oncology and European Society for Medical Oncology meetings' libraries, Kaplan-Meier curves were extracted from phase 3 clinical trials conducted from January 1, 2011, until September 12, 2023.
STUDY SELECTION
Phase 3 clinical trials that tested NALIRIFOX, FOLFIRINOX, or GEM-NABP as first-line treatment of metastatic PDAC and reported overall survival (OS) and progression-free survival (PFS) curves were selected. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses of Individual Participant Data reporting guidelines.
DATA EXTRACTION AND SYNTHESIS
Individual patient OS and PFS data were extracted from Kaplan-Meier plots of original trials via a graphic reconstructive algorithm. Overall response rates (ORRs) and grade 3 or higher toxic effects rates were also collected. A pooled analysis was conducted, and results were validated via a network meta-analysis.
MAIN OUTCOMES AND MEASURES
The primary end point was OS. Secondary outcomes included PFS, ORR, and toxic effects rates.
RESULTS
A total of 7 trials with data on 2581 patients were analyzed, including 383 patients treated with NALIRIFOX, 433 patients treated with FOLFIRINOX, and 1756 patients treated with GEM-NABP. Median PFS was longer in patients treated with NALIRIFOX (7.4 [95% CI, 6.1-7.7] months) or FOLFIRINOX (7.3 [95% CI, 6.5-7.9] months; [HR], 1.21 [95% CI, 0.86-1.70]; P = .28) compared with patients treated with GEM-NABP (5.7 [95% CI, 5.6-6.1] months; HR vs NALIRIFOX, 1.45 [95% CI, 1.22-1.73]; P < .001). Similarly, GEM-NABP was associated with poorer OS (10.4 [95% CI, 9.8-10.8]; months) compared with NALIRIFOX (HR, 1.18 [95% CI, 1.00-1.39]; P = .05], while no difference was observed between FOLFIRINOX (11.7 [95% CI, 10.4-13.0] months) and NALIRIFOX (11.1 [95% CI, 10.1-12.3] months; HR, 1.06 [95% CI, 0.81-1.39]; P = .65). There were no statistically significant differences in ORR among NALIRIFOX (41.8%), FOLFIRINOX (31.6%), and GEM-NABP (35.0%). NALIRIFOX was associated with lower incidence of grade 3 or higher hematological toxic effects (eg, platelet count decreased 1.6% vs 11.8% with FOLFIRINOX and 10.8% with GEM-NABP), but higher rates of severe diarrhea compared with GEM-NABP (20.3% vs 15.7%).
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis, NALIRIFOX and FOLFIRINOX were associated with similar PFS and OS as first-line treatment of advanced PDAC, although NALIRIFOX was associated with a different toxicity profile. Careful patient selection, financial toxic effects consideration, and direct comparison between FOLFIRINOX and NALIRIFOX are warranted.
Topics: Humans; Pancreatic Neoplasms; Irinotecan; Antineoplastic Combined Chemotherapy Protocols; Leucovorin; Oxaliplatin; Gemcitabine; Fluorouracil; Adenocarcinoma
PubMed: 38190183
DOI: 10.1001/jamanetworkopen.2023.50756 -
Urologic Oncology Apr 2024Nanocarriers (NCs) are a form of nanotechnology widely investigated in cancer treatment to improve the safety and efficacy of systemic therapies by increasing tumor... (Review)
Review
Nanocarriers (NCs) are a form of nanotechnology widely investigated in cancer treatment to improve the safety and efficacy of systemic therapies by increasing tumor specificity. Numerous clinical trials have explored the use of NCs in urologic cancers since the approval of the first NCs for cancer treatment over 20 years ago. The objective of this systematic review is to examine the effectiveness and safety of NCs in treating urological cancers. This paper summarizes the state of the field by investigating peer-reviewed, published results from 43 clinical trials involving the use of NCs in bladder, prostate, and kidney cancer patients with a focus on safety and efficacy data. Among the 43 trials, 16 were phase I, 20 phase II, and 4 phase I/II. No phase III trials have been reported. While both novel and classic NCs have been explored in urologic cancers, NCs already approved for the treatment of other cancers were more widely represented. Trials in prostate cancer and mixed trials involving both urologic and non-urologic cancer patients were the most commonly reported trials. Although NCs have demonstrable efficacy with adequate safety in non-urologic cancer patient populations, current clinical stage NC options appear to be less beneficial in the urologic cancer setting. For example, nab-paclitaxel and liposomal doxorubicin have proven ineffective in the treatment of urologic cancers despite successes in other cancers. However, several ongoing pre-clinical studies using targeted and locally applied improved NCs may eventually improve their utility.
Topics: Male; Humans; Urologic Neoplasms; Prostatic Neoplasms
PubMed: 38161104
DOI: 10.1016/j.urolonc.2023.11.022 -
Langmuir : the ACS Journal of Surfaces... Jan 2024Chemotherapy is the most widely used cancer treatment, but it has several drawbacks such as adverse side effects and low bioavailability. To address these limitations,...
Chemotherapy is the most widely used cancer treatment, but it has several drawbacks such as adverse side effects and low bioavailability. To address these limitations, various drug delivery systems have been investigated, including liposomes, micelles, and emulsions. These drug delivery technologies have been improving the efficacy and safety of conventional chemotherapy. This study presents an emerging drug delivery technology for targeted chemotherapy using drug-loaded ultrasound-responsive emulsion (URE) as a drug carrier and ultrasound technology for external activation. URE was designed to be responsive to ultrasound energy and fabricated by using an emulsification technique. To investigate this technology, paclitaxel, as a model drug, was used and encapsulated into URE. The size distribution, morphology, and drug release behavior of paclitaxel-loaded URE (PTX-URE) were characterized, and the echogenicity of PTX-URE was assessed by using ultrasound imaging equipment. The cellular uptake and cytotoxicity of PTX-URE with ultrasound were evaluated in breast cancer cells (MDA-MB-231). Our results indicate that the combination of PTX-URE and ultrasound significantly enhanced cellular uptake by 10.6-fold and improved cytotoxicity by 24.1% compared to PTX alone. These findings suggest that the URE platform combined with ultrasound is a promising technology to improve the drug delivery efficiency for chemotherapy.
Topics: Paclitaxel; Emulsions; Cell Line, Tumor; Drug Delivery Systems; Ultrasonography; Drug Carriers; Micelles
PubMed: 38146661
DOI: 10.1021/acs.langmuir.3c02005 -
Archiv Der Pharmazie Mar 2024It is well known that bone-related diseases are difficult to treat due to the relatively low blood flow. Therefore, targeting the delivery of drugs to bone may not only...
It is well known that bone-related diseases are difficult to treat due to the relatively low blood flow. Therefore, targeting the delivery of drugs to bone may not only improve the therapeutic effect but also reduce the dose. To prepare liposomes, a series of novel multivalent glutamic hexapeptide derivatives were designed and synthesized as liposome ligands, which can effectively deliver paclitaxel (PTX) to bone. The liposomes were prepared and their encapsulation efficiency, particle size, stability, zeta potential, hemolysis, and release behavior were characterized. The results indicated that the coated liposomes, PTX-Glu6 -Lip, PTX-Glu6 -Lip, PTX-Glu6 -Lip, and PTX-Glu6 -Lip, showed remarkable bone-targeting activity. Compared with the other coated liposomes, PTX-Glu6 -Lip showed prominent targeting ability and anti-bone metastasis activity on the basis of in vitro and in vivo evaluations. Our study may contribute to the field of design of bone-targeting drugs.
Topics: Liposomes; Structure-Activity Relationship; Drug Delivery Systems; Paclitaxel
PubMed: 38133558
DOI: 10.1002/ardp.202300620 -
Oncology Letters Jan 2024Lung cancer is the most common type of cancer worldwide. Lung adenocarcinoma, a type of non-small cell lung cancer (NSCLC), is a common type of lung cancer. In recent...
Lung cancer is the most common type of cancer worldwide. Lung adenocarcinoma, a type of non-small cell lung cancer (NSCLC), is a common type of lung cancer. In recent years, immunotherapy has become the primary method of treatment for several solid cancers, including NSCLC. In the present study, the case of a patient with NSCLC following left superior lobectomy is reported. Different systemic therapies failed, such as a pemetrexed + carboplatin regimen, paclitaxel liposome + cisplatin and pembrolizumab, and albumin-bound paclitaxel + toripalimab, but long-term survival was achieved following targeted therapy and anti-programmed cell death protein-1 (PD-1) immunotherapy. The patient survived for >4 years following lung cancer progression, which is notably longer than expected for patients with advanced lung cancer. In conclusion, the present case demonstrated the efficacy of targeted therapy and anti-PD-1 immunotherapy for the treatment of advanced lung cancer following the occurrence of drug resistance and progressive disease.
PubMed: 38108071
DOI: 10.3892/ol.2023.14166 -
The European Physical Journal. E, Soft... Dec 2023Paclitaxel (PTX) is a hydrophobic small-molecule cancer drug that loads into the membrane (tail) region of lipid carriers such as liposomes and micelles. The development...
Paclitaxel (PTX) is a hydrophobic small-molecule cancer drug that loads into the membrane (tail) region of lipid carriers such as liposomes and micelles. The development of improved lipid-based carriers of PTX is an important objective to generate chemotherapeutics with fewer side effects. The lipids 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and glyceryl monooleate (GMO) show propensity for fusion with other lipid membranes, which has led to their use in lipid vectors of nucleic acids. We hypothesized that DOPE and GMO could enhance PTX delivery to cells through a similar membrane fusion mechanism. As an important measure of drug carrier performance, we evaluated PTX solubility in cationic liposomes containing GMO or DOPE. Solubility was determined by time-dependent kinetic phase diagrams generated from direct observations of PTX crystal formation using differential-interference-contrast optical microscopy. Remarkably, PTX was much less soluble in these liposomes than in control cationic liposomes containing univalent cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC), which are not fusogenic. In particular, PTX was not substantially soluble in GMO-based cationic liposomes. The fusogenicity of DOPE and GMO is related to the negative spontaneous curvature of membranes containing these lipids, which drives formation of nonlamellar self-assembled phases (inverted hexagonal or gyroid cubic). To determine whether PTX solubility is governed by lipid membrane structure or by local intermolecular interactions, we used synchrotron small-angle X-ray scattering. To increase the signal/noise ratio, we used DNA to condense the lipid formulations into lipoplex pellets. The results suggest that local intermolecular interactions are of greater importance and that the negative spontaneous curvature-inducing lipids DOPE and GMO are not suitable components of liposomal carriers for PTX delivery.
Topics: Paclitaxel; Liposomes; Solubility; Antineoplastic Agents; Micelles; Neoplasms
PubMed: 38099960
DOI: 10.1140/epje/s10189-023-00388-2