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Nanomedicine (London, England) Apr 2022The present study aimed to retrospectively compare the efficacy and safety between liposomal paclitaxel (Lps-P) and nanoparticle albumin-bound paclitaxel (Nab-P) in...
The present study aimed to retrospectively compare the efficacy and safety between liposomal paclitaxel (Lps-P) and nanoparticle albumin-bound paclitaxel (Nab-P) in neoadjuvant systemic treatment (NST) of breast cancer. Two hundred thirty-five patients who were diagnosed with invasive breast cancer and then received dose-dense NST with epirubicin and cyclophosphamide followed by paclitaxel were enrolled. Nab-P has an advantage in improving the total and axillary-only pathologic complete response rate over Lps-P. Although Nab-P can cause a higher incidence and severity of peripheral sensory neuropathy (PSN), most symptoms are temporary and reversible. In the Lps-P group, the proportion of patients with residual irreversible PSN is larger. Nab-P might be superior to Lps-P in NST of breast cancer.
Topics: Albumin-Bound Paclitaxel; Albumins; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Female; Humans; Lipopolysaccharides; Nanoparticles; Neoadjuvant Therapy; Paclitaxel; Retrospective Studies; Treatment Outcome
PubMed: 35393861
DOI: 10.2217/nnm-2022-0025 -
Asian Journal of Pharmaceutical Sciences Sep 2017Paclitaxel (PTX) is an important cancer chemotherapeutic drug. To ameliorate the disadvantages of paclitaxel, this study designed liposomes to load paclitaxel, adding...
Paclitaxel (PTX) is an important cancer chemotherapeutic drug. To ameliorate the disadvantages of paclitaxel, this study designed liposomes to load paclitaxel, adding the acid-sensitive material cholesteryl hemisuccinate (CHEMS) to increase the accumulation of the drug in the tumor site. To begin, we used a high-performance liquid chromatography (HPLC) method to determine the content of PTX and the encapsulation efficiency. Then, we prepared paclitaxel-loaded acid-sensitive liposomes (PTX ASLs) by a thin-film dispersion method. We investigated the physical and chemical properties of the liposomes. The particle size was 210.8 nm, the polydispersity index (PDI) was 0.182 and the ζ-potential was -31.2 mV. The liposome shape was observed by transmission electron microscopy (TEM), and the results showed that the liposomes were round with a homogenous size distribution. The release characteristics of the liposomes were studied via a dynamic dialysis method. The results showed that the prepared liposomes had acid sensitivity and sustained release properties. An cellular uptake assay of MCF-7 cells showed that the cell uptake of coumarin-6-loaded acid-sensitive liposomes was significantly higher than that of free coumarin-6. The cytotoxicity of the PTX ASLs was significantly higher than that of paclitaxel. In conclusion, these results showed that the prepared liposomes had clear acid-sensitive release characteristics and a higher cell uptake rate and cytotoxicity than free PTX. The system is very suitable for targeted cancer therapy with paclitaxel.
PubMed: 32104360
DOI: 10.1016/j.ajps.2017.05.008 -
Pharmaceutical Development and... Jan 2022'One drug- one target' to 'multiple drug- multiple targets' paradigm shifted to produce combination therapies, have found great outcomes to overcome multiple drug... (Review)
Review
'One drug- one target' to 'multiple drug- multiple targets' paradigm shifted to produce combination therapies, have found great outcomes to overcome multiple drug resistance (MDR). MDR is a significant barrier to the delivery of taxane-based anticancer medicines such as docetaxel, paclitaxel, and cabazitaxel. Due to MDR induced by drug efflux transporters, clinical application of these medications is impeded. To date, nanoformulations such as liposomes, micelles, polymeric nanoparticles, and gold nanoparticles have been investigated to deliver taxanes alone and in combination to reverse drug resistance. Despite the fact that various groups have already looked into taxane nano formulations in the literature, there isn't much in the way of polypharmacology and advanced nanoformulations with a focus on MDR. In this overview, we briefly covered the insights regarding MDR, difficulties related to current pharmaceutical products of taxanes, combination therapies of taxanes to combat MDR, all of which can be used to delve into cancer treatment.
Topics: Antineoplastic Agents; Drug Resistance, Neoplasm; Gold; Metal Nanoparticles; Micelles; Nanotechnology; Neoplasms; Paclitaxel; Taxoids
PubMed: 34806547
DOI: 10.1080/10837450.2021.2009861 -
Drug Discovery Today Feb 2022The diterpenoid molecule paclitaxel (PTX), extracted from the Western yew tree, Taxus brevifolia, is a promising anticancer drug specifically in clinical use for ovarian... (Review)
Review
The diterpenoid molecule paclitaxel (PTX), extracted from the Western yew tree, Taxus brevifolia, is a promising anticancer drug specifically in clinical use for ovarian and breast cancers. However, its wider use is hampered by adverse effects and emerging resistance in cancer cells. Micelles, liposomes, cubosomes, and lipid nanoparticles (LNPs) have the potential to reduce or even remove complications associated with the use of PTX. Herein, we provide an overview of micro- and nanoformulations of PTX based on micelles, liposomes, cubosomes and LNPs to improve the therapeutic effects of this drug both in vitro and in vivo.
Topics: Cell Line, Tumor; Drug Carriers; Humans; Liposomes; Micelles; Nanoparticles; Paclitaxel; Polyethylene Glycols
PubMed: 34688912
DOI: 10.1016/j.drudis.2021.10.007 -
Journal of Controlled Release :... Jun 2019Chemotherapy-induced peripheral neuropathy (CIPN) is a major adverse effect of paclitaxel. Several liposome-based products have been approved and demonstrated superior...
Chemotherapy-induced peripheral neuropathy (CIPN) is a major adverse effect of paclitaxel. Several liposome-based products have been approved and demonstrated superior efficacy and safety profiles for other drugs. The first objective of this work was to evaluate the effect of liposome formulation of paclitaxel (L-PTX) on neurotoxicity in-vitro and in-vivo in comparison to the standard Taxol® formulation. The second aim was to investigate the effect of formulation on paclitaxel biodistribution following intravenous administration in an animal model. Free paclitaxel was toxic to cell of neuronal origin (IC50 = 18.4 μg/mL) at a lower concentration than to lung cancer cells (IC50 = 59.1 μg/mL), and L-PTX demonstrated a comparable toxicity in both cell lines (IC50 = 31.8 and 33.7 μg/mL). Administration of L-PTX at 2 mg/kg per dose for a total of 4 doses on day 0, 2, 4, and 6 to rats did not result in increased sensitivity in response to mechanical or thermal stimulation of hind paws, in comparison to Taxol® administration at the same dose level that resulted in neuropathy. Paclitaxel biodisposition was evaluated for two formulations in plasma, liver, lung, brain, spinal cord, skin and muscle of rats after single intravenous dose at 6 mg/kg. The exposure to paclitaxel in brain, spinal cord, muscle, and skin was lower in the L-PTX group compared to Taxol® group. PEGylated liposomes containing paclitaxel were successfully developed and demonstrated reduced neurotoxicity in-vitro in neuronal cells and prevented development of peripheral neuropathy in-vivo. This proof of concept study showed that formulation in nanoparticles is a promising approach for reducing (or preventing) neurotoxicity caused by cancer drugs.
Topics: Animals; Antineoplastic Agents, Phytogenic; Brain; Cell Line, Tumor; Drug Compounding; Humans; Liposomes; Liver; Lung; Male; Muscles; Nanoparticles; Paclitaxel; Peripheral Nervous System Diseases; Rats, Sprague-Dawley; Skin; Spinal Cord; Tissue Distribution
PubMed: 30981814
DOI: 10.1016/j.jconrel.2019.04.013 -
Lakartidningen Jul 2017Nanoparticles for cancer therapy Nanoparticles carry a big promise in oncology, for diagnosis/imaging, therapy, or both (theragnostics). As common in medical history,...
Nanoparticles for cancer therapy Nanoparticles carry a big promise in oncology, for diagnosis/imaging, therapy, or both (theragnostics). As common in medical history, there is a huge gap between the exciting experimental possibilities and data and clinical studies making use of it. Of the cell-containing nanoparticles, only one formulation using gene-directed enzyme prodrug therapy (GDEPT) with CYP2B1 and ifosfamide was used in early clinical studies. Of the cell-free nanoparticles, some drug-releasing (doxorubicin) ones are in clinical use for trans-arterial chemo-embolization (TACE) in liver tumors and metastasis. Using liposomes, both paclitaxel and irinotecan have been used in pancreatic cancer as the model indication. Nanoparticle-albumin-bound paclitaxel (NAB-paclitaxel) has also been developed and is now registered as a drug for first-line therapy of pancreatic cancer, as is the liposomal irinotecan. The novel nanoparticle formulations carry a big promise for even better performance, both in diagnosis and therapy; however, few of these has entered the clinic as of today.
Topics: Antineoplastic Agents; Humans; Liposomes; Nanocapsules; Nanomedicine; Nanoparticles; Neoplasms; Pancreatic Neoplasms
PubMed: 28675414
DOI: No ID Found -
Journal of Liposome Research Mar 2019This study aimed to develop novel temperature-sensitive liposomes loading paclitaxel (PTX-TSL) and evaluate them in vitro to improve the delivery efficiency and...
This study aimed to develop novel temperature-sensitive liposomes loading paclitaxel (PTX-TSL) and evaluate them in vitro to improve the delivery efficiency and targeting of PTX. K237 peptide was conjugated to the terminal NHS of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[hydroxyl succinimidyl (polyethylene glycol)-(DSPE-PEG-NHS), and K237-modified PTX-TSL (K237-PTX-TSL) was prepared using a film dispersion method. K237-TSL encapsulation with calcein was synthesized and used to determine the cellular uptake of TSL. The morphology of K237-PTX-TSL was observed using a transmission electron microscope. The particle size and potential were measured using a laser particle size analyzer. The phase transition temperature was detected using the differential scanning calorimetry. The Cell Counting Kit-8 assay and flow cytometry were used to evaluate the effects of K237-PTX-TSL on the proliferation and cell cycle of cell lines SKOV-3 and human umbilical vein endothelial cell (HUVEC). The encapsulation efficiency of K237-PTX-TSL was 94.23% ± 0.76%. The particle diameter was 88.3 ± 4.7 nm. K237-PTX-TSL showed a fast release profile at 42 °C, while it was stable at 37 °C. PTX-TSL combined with hyperthermia significantly inhibited the cell proliferation of SKOV-3 cells and HUVECs due to increased cell arrest in the G2/M phase. The half-minimal inhibitory concentration value of K237-PTX-TSL on SKOV-3 cells and HUVECs was 13.61 ± 1.81 and 5.54 ± 0.95 nmol/L, respectively, which were significantly lower than those with PTX-TSL (p < 0.01). K237 modification could increase the targeting efficiency of TSL to cancer cells and vascular endothelial cells, thus resulting in higher cytotoxicities compared with PTX-TSL, which might be a potential formulation for targeting cancer therapy.
Topics: Animals; Antineoplastic Agents, Phytogenic; Cell Line; Humans; Liposomes; Oligopeptides; Paclitaxel; Phosphatidylethanolamines; Polyethylene Glycols; Transition Temperature
PubMed: 29671386
DOI: 10.1080/08982104.2018.1458863 -
Molecules (Basel, Switzerland) Nov 2022A series of novel paclitaxel derivatives modified by boronic acid according to the characteristics of the interaction between RB(OH)2 and different strapping agents of...
A series of novel paclitaxel derivatives modified by boronic acid according to the characteristics of the interaction between RB(OH)2 and different strapping agents of intraliposomal aqueous phase were designed and synthesized, which were then used to develop remote poorly water-soluble drugs loading into liposomes. Meanwhile, we screened nineteen paclitaxel boronic acid derivatives for their cytotoxic activities against three cancer cell lines (A549, HCT-116 and 4T1) and one normal cell line (LO2), and performed liposome formulation screening of active compounds. Among all the compounds, the liposome of 4d, with excellent drug-encapsulated efficiency (>95% for drug-to-lipid ratio of 0.1 w/w), was the most stable. Furthermore, the liposomes of compound 4d (8 mg/kg, 4 times) and higher dose of compound 4d (24 mg/kg, 4 times) showed better therapeutic effect than paclitaxel (8 mg/kg, 4 times) in the 4T1 tumor model in vivo, and the rates of tumor inhibition were 74.3%, 81.9% and 58.5%, respectively. This study provided a reasonable design strategy for the insoluble drugs to improve their drug loading into liposomes and anti-tumor effect in vivo.
Topics: Liposomes; Paclitaxel; Drug Stability; Boronic Acids
PubMed: 36432067
DOI: 10.3390/molecules27227967 -
Journal of Materials Chemistry. B Sep 2023Photodynamic therapy is an effective method for the treatment of several types of cancerous and noncancerous diseases. The key to the success of this treatment method is... (Review)
Review
Photodynamic therapy is an effective method for the treatment of several types of cancerous and noncancerous diseases. The key to the success of this treatment method is effective drug delivery to the site of action, for instance, a tumor. This ensures not only the high effectiveness of the therapy but also the suppression of side effects. But how to achieve effective targeted delivery? Lately, much attention has been paid to systems based on the so-called Trojan horse model, which is gaining increasing popularity. The principle of this model is that the effective drug is hidden in the internal structure of a nanoparticle, liposome, or nanoemulsion and is released only at the site of action. In this review article, we focus on drugs from the group of mitotic poisons, taxanes, and their use with photosensitizers in combined therapy. Here, we discuss the possibilities of how to improve the paclitaxel and docetaxel bioavailability, as well as their specific targeting for use in combined photo- and chemotherapy. Moreover, we also present the state of the art multifunctional drugs based on cabazitaxel which, owing to a suitable combination with photosensitizers, can be used besides photodynamic therapy and also in photoacoustic imaging or sonodynamic therapy.
Topics: Photosensitizing Agents; Photochemotherapy; Drug Delivery Systems; Taxoids; Paclitaxel
PubMed: 37615658
DOI: 10.1039/d2tb02147a -
Journal of Materials Chemistry. B May 2021Nanozymes, as a kind of artificial mimic enzymes, have superior catalytic capacity and stability. As lack of O2 in tumor cells can cause resistance to drugs, we designed...
Nanozymes, as a kind of artificial mimic enzymes, have superior catalytic capacity and stability. As lack of O2 in tumor cells can cause resistance to drugs, we designed drug delivery liposomes (MnO2-PTX/Ce6@lips) loaded with catalase-like nanozymes of manganese dioxide nanoparticles (MnO2 NPs), paclitaxel (PTX) and chlorin e6 (Ce6) to consume tumor's native H2O2 and produce O2. Based on the catalysis of MnO2 NPs, a large amount of oxygen was produced by MnO2-PTX/Ce6@lips to burst the liposomes and achieve a responsive release of the loaded drug (paclitaxel), and the released O2 relieved the chemoresistance of tumor cells and provided raw materials for photodynamic therapy. Subsequently, MnO2 NPs were decomposed into Mn2+ in an acidic tumor environment to be used as contrast agents for magnetic resonance imaging. The MnO2-PTX/Ce6@lips enhanced the efficacy of chemotherapy and photodynamic therapy (PDT) in bearing-tumor mice, even achieving complete cure. These results indicated the great potential of MnO2-PTX/Ce6@lips for the modulation of the TME and the enhancement of chemotherapy and PDT along with MRI tracing in the treatment of tumors.
Topics: Animals; Antineoplastic Agents, Phytogenic; Cell Survival; Chlorophyllides; Contrast Media; Humans; Hydrogen Peroxide; Light; Liposomes; Magnetic Resonance Imaging; Manganese Compounds; Mice; Nanoparticles; Nanostructures; Neoplasms; Oxides; Oxygen; Paclitaxel; Photochemotherapy; Photosensitizing Agents; Porphyrins; Theranostic Nanomedicine
PubMed: 33942817
DOI: 10.1039/d0tb02791j