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Journal of Materials Science. Materials... Dec 2021In this study, paclitaxel (PTX)-loaded pH-responsive niosomes modified with ergosterol were developed. This new formulation was characterized in terms of size,...
In this study, paclitaxel (PTX)-loaded pH-responsive niosomes modified with ergosterol were developed. This new formulation was characterized in terms of size, morphology, encapsulation efficiency (EE), and in vitro release at pH 5.2 and 7.4. The in vitro efficacy of free PTX and niosome/PTX was assessed using MCF7, Hela, and HUVEC cell lines. In order to evaluate the in vivo efficacy of niosomal PTX in rats as compared to free PTX, the animals were intraperitoneally administered with 2.5 mg/kg and 5 mg/kg niosomal PTX for two weeks. Results showed that the pH-responsive niosomes had a nanometric size, spherical morphology, 77% EE, and pH-responsive release in pH 5.2 and 7.4. Compared with free PTX, we found markedly lower IC50s when cancer cells were treated for 48 h with niosomal PTX, which also showed high efficacy against human cancers derived from cervix and breast tumors. Moreover, niosomal PTX induced evident morphological changes in these cell lines. In vivo administration of free PTX at the dose of 2.5 mg/kg significantly increased serum biochemical parameters and liver lipid peroxidation in rats compared to the control rats. The situation was different when niosomal PTX was administered to the rats: the 5 mg/kg dosage of niosomal PTX significantly increased serum biochemical parameters, but the group treated with the 2.5 mg/kg dose of niosomal PTX showed fewer toxic effects than the group treated with free PTX at the same dosage. Overall, our results provide proof of concept for encapsulating PTX in niosomal formulation to enhance its therapeutic efficacy.
Topics: Animals; Antineoplastic Agents; Drug Liberation; HeLa Cells; Human Umbilical Vein Endothelial Cells; Humans; Hydrogen-Ion Concentration; Lipid Peroxidation; Liposomes; MCF-7 Cells; Male; Paclitaxel; Rats; Rats, Sprague-Dawley
PubMed: 34862910
DOI: 10.1007/s10856-021-06623-6 -
Molecules (Basel, Switzerland) Apr 2022The problems with anticancer therapy are resistance and toxicity. From 3000 Cisplatin derivatives tested as antitumor agents, most of them have been rejected, due to... (Review)
Review
The problems with anticancer therapy are resistance and toxicity. From 3000 Cisplatin derivatives tested as antitumor agents, most of them have been rejected, due to toxicity. The aim of current study is the comparison of therapeutic combinations of the currently applied in clinical practice: Cisplatin, Carboplatin, Oxaliplatin, Nedaplatin, Lobaplatin, Heptaplatin, and Satraplatin. The literature data show that the strategies for the development of platinum anticancer agents and bypassing of resistance to Cisplatin derivatives and their toxicity are: combination therapy, Pt IV prodrugs, the targeted nanocarriers. The very important strategy for the improvement of the antitumor effect against different cancers is synergistic combination of Cisplatin derivatives with: (1) anticancer agents-Fluorouracil, Gemcitabine, Cytarabine, Fludarabine, Pemetrexed, Ifosfamide, Irinotecan, Topotecan, Etoposide, Amrubicin, Doxorubicin, Epirubicin, Vinorelbine, Docetaxel, Paclitaxel, Nab-Paclitaxel; (2) modulators of resistant mechanisms; (3) signaling protein inhibitors-Erlotinib; Bortezomib; Everolimus; (4) and immunotherapeutic drugs-Atezolizumab, Avelumab, Bevacizumab, Cemiplimab, Cetuximab, Durvalumab, Erlotinib, Imatinib, Necitumumab, Nimotuzumab, Nivolumab, Onartuzumab, Panitumumab, Pembrolizumab, Rilotumumab, Trastuzumab, Tremelimumab, and Sintilimab. An important approach for overcoming the drug resistance and reduction of toxicity of Cisplatin derivatives is the application of nanocarriers (polymers and liposomes), which provide improved targeted delivery, increased intracellular penetration, selective accumulation in tumor tissue, and enhanced therapeutic efficacy. The advantages of combination therapy are maximum removal of tumor cells in different phases; prevention of resistance; inhibition of the adaptation of tumor cells and their mutations; and reduction of toxicity.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Cisplatin; Erlotinib Hydrochloride; Humans; Neoplasms
PubMed: 35458666
DOI: 10.3390/molecules27082466 -
Journal of Functional Biomaterials Aug 2022Cancer is a common disease in dogs, with a growing incidence related to the age of the animal. Nanotechnology is being employed in the veterinary field in the same... (Review)
Review
BACKGROUND
Cancer is a common disease in dogs, with a growing incidence related to the age of the animal. Nanotechnology is being employed in the veterinary field in the same manner as in human therapy.
AIM
This review focuses on the application of biocompatible nanocarriers for the treatment of canine cancer, paying attention to the experimental studies performed on dogs with spontaneously occurring cancer.
METHODS
The most important experimental investigations based on the use of lipid and non-lipid nanosystems proposed for the treatment of canine cancer, such as liposomes and polymeric nanoparticles containing doxorubicin, paclitaxel and cisplatin, are described and their in vivo fate and antitumor features discussed.
CONCLUSIONS
Dogs affected by spontaneous cancers are useful models for evaluating the efficacy of drug delivery systems containing antitumor compounds.
PubMed: 35997454
DOI: 10.3390/jfb13030116 -
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 -
Asian Pacific Journal of Cancer... Sep 2023Addressing both the initial treatment response and subsequent paclitaxel resistance is a pivotal concern. Nano drug delivery, an emerging approach, presents a...
OBJECTIVE
Addressing both the initial treatment response and subsequent paclitaxel resistance is a pivotal concern. Nano drug delivery, an emerging approach, presents a cutting-edge alternative to conventional chemotherapy.
METHODS
This investigation synthesized PEGylated nanoparticles (NPs) via the Reverse Phase Evaporation technique for liposomal NPs. Characteristics such as zeta potential, size, drug release and polydispersity index (PDI) were subjected to evaluation. Subsequently, cytotoxicity assays were conducted on gastric cancer cells (AGS) following 24 and 48-hour incubation periods.
RESULTS
In this study, the liposomal NPs had a zeta potential of -22 mV and a particle size of 285 nm. The Entrapment efficiency was determined as 41% that occurred physically. Additionally, the liposomal NPs demonstrated a high drug retention rate (39% remained after 72 hours), and they exhibited significantly increased cytotoxicity compared to the free drug, confirming their effectiveness as a suitable carrier for paclitaxel during both incubation periods (P<0.05).
CONCLUSION
These findings collectively advocate the potential of liposomal NPs as promising contenders for effective nano-drug application in propelling chemotherapy forward.
Topics: Humans; Stomach Neoplasms; Antineoplastic Agents; Paclitaxel; Liposomes; Nanoparticles; Particle Size; Drug Carriers
PubMed: 37774084
DOI: 10.31557/APJCP.2023.24.9.3291 -
Gels (Basel, Switzerland) Mar 2021The discovery of paclitaxel (PTX) has been a milestone in anti-cancer therapy and has promoted the development and marketing of various formulations that have... (Review)
Review
The discovery of paclitaxel (PTX) has been a milestone in anti-cancer therapy and has promoted the development and marketing of various formulations that have revolutionized the therapeutic approach towards several malignancies. Despite its peculiar anti-cancer activity, the physico-chemical properties of PTX compromise the administration of the compound in polar media. Because of this, since the development of the first Food and Drug Administration (FDA)-approved formulation (Taxol), consistent efforts have been made to obtain suitable delivery systems able to preserve/increase PTX efficacy and to overcome the side effects correlated to the presence of some excipients. The exploitation of natural polymers as potential materials for drug delivery purposes has favored the modulation of the bioavailability and the pharmacokinetic profiles of the drug, and in this regard, several formulations have been developed that allow the controlled release of the active compound. In this mini-review, the recent advances concerning the design and applications of natural polymer-based hydrogels containing PTX-loaded biocompatible nanocarriers are discussed. The technological features of these formulations as well as the therapeutic outcome achieved following their administration will be described, demonstrating their potential role as innovative systems to be used in anti-tumor therapy.
PubMed: 33804970
DOI: 10.3390/gels7020033 -
Turkish Journal of Pharmaceutical... Mar 2023Paclitaxel (PTX) is used as a viable cancer medication in the chemotherapy of breast, ovarian, lung, bladder, neck, head, and esophageal tumors. The focus of this review...
Paclitaxel (PTX) is used as a viable cancer medication in the chemotherapy of breast, ovarian, lung, bladder, neck, head, and esophageal tumors. The focus of this review is to survey various folate-targeting PTX-loaded nanopreparations in both research and clinical applications. There are diverse nanopreparations, including liposomes, micelles, polymeric nanopreparations, lipid nanopreparations, lipoprotein nanocarriers, and other inorganic nanopreparations for folate-associated PTX tumor targeting. Here, the folate targeting PTX-loaded nanopreparations, which have promising results in the constructive treatment of cancer by reducing toxic side-effects and/or improving effectiveness, was mainly reviewed.
PubMed: 36864596
DOI: 10.4274/tjps.galenos.2021.26529 -
Evidence-based Complementary and... 2022The aim of this study is to investigate the effect of paclitaxel combined with doxorubicin hydrochloride liposome injection (DHLI) in the treatment of osteosarcoma and...
OBJECTIVE
The aim of this study is to investigate the effect of paclitaxel combined with doxorubicin hydrochloride liposome injection (DHLI) in the treatment of osteosarcoma and the MRI changes before and after treatment.
METHODS
A total of 108 osteosarcoma patients treated in our hospital (January 2020-April 2022) were selected to carry out a single-center retrospective study. Among them, 54 patients receiving the combination chemotherapy (MDT) with high-dose methotrexate, ifosfamide, cisplatin, and ADM were selected as the control group (COG), while 54 patients receiving MDT with high-dose methotrexate, ifosfamide, cisplatin, paclitaxel, and DHLI were chosen as the study group (STG). The COG and STG had the same dose intensity and chemotherapy cycles, and clinical and MRI evaluations were performed after treatment.
RESULTS
The evaluation of postoperative clinical efficacy showed that the disease control rate (DCR) of the STG was markedly higher than that of the COG ( < 0.05). The incidence of cardiac toxicity was remarkably lower in the STG than that in the COG ( < 0.05), with no between-group differences in the incidence of fever, abnormal liver function, myelosuppression, stomatitis, and alopecia ( > 0.05). Obvious differences were found in the semiquantitative parameters of MRI in the STG before and after chemotherapy ( < 0.05) and were also found in the SI, TTP, SEE, PPE, WOR, and values in the COG before and after chemotherapy ( < 0.05). After chemotherapy, statistical differences were observed in the semiquantitative parameters of MRI between the two groups, with lower parameters such as Slope, SI, SEE, and values and higher parameters such as TTP, PPE, and WOR values in the STG than those in the COG ( < 0.05).
CONCLUSION
Paclitaxel combined with DHLI has definite efficacy in osteosarcoma chemotherapy, which is conducive to narrowing the lesion, controlling the disease, and reducing the occurrence of cardiac-related risk events. In addition, the semiquantitative parameters of dynamic contrast-enhanced MRI (DCE-MRI) have a high predictive value for the efficacy of chemotherapy, which can reflect the degree of tumor necrosis and contribute to a timely and objective assessment of the efficacy of osteosarcoma chemotherapy.
PubMed: 35942377
DOI: 10.1155/2022/5651793 -
The Cochrane Database of Systematic... Jul 2022Ovarian cancer is the seventh most frequent cancer diagnosis worldwide, and the eighth leading cause of cancer mortality. Epithelial ovarian cancer is the most common... (Review)
Review
BACKGROUND
Ovarian cancer is the seventh most frequent cancer diagnosis worldwide, and the eighth leading cause of cancer mortality. Epithelial ovarian cancer is the most common kind, accounting for 90% of cases. First-line therapy for women with epithelial ovarian cancer consists of a combination of cytoreductive surgery and platinum and taxane-based chemotherapy. However, more than 50% of women with epithelial ovarian cancer will experience a relapse and require further chemotherapy and at some point develop resistance to platinum-based drugs. Currently, guidance on the use of most chemotherapy drugs, including taxanes, is unclear for women whose epithelial ovarian cancer has recurred. Paclitaxel, topotecan, pegylated liposomal doxorubicin hydrochloride, trabectedin and gemcitabine are all licensed for use in the UK at the discretion of clinicians, following discussion with the women as to potential adverse effects. Taxanes can be given in once-weekly regimens (at a lower dose) or three-weekly regimens (at a higher dose), which may have differences in the severity of side effects and effectiveness. As relapsed disease suggests incurable disease, it is all the more important to consider side effects and the impact of treatment schedules, as well as quality of life, and not only the life-prolonging effects of treatment.
OBJECTIVES
To assess the efficacy and toxicity of different taxane monotherapy regimens for women with recurrent epithelial ovarian, tubal or primary peritoneal cancer.
SEARCH METHODS
We searched CENTRAL, MEDLINE and Embase, up to 22 March 2022. Other related databases and trial registries were searched as well as grey literature and no additional studies were identified. A total of 1500 records were identified.
SELECTION CRITERIA
We included randomised controlled trials of taxane monotherapy for adult women diagnosed with recurrent epithelial ovarian, tubal or primary peritoneal cancer, previously treated with platinum-based chemotherapy. We included trials comparing two or more taxane monotherapy regimens. Participants could be experiencing their first recurrence of disease or any line of recurrence.
DATA COLLECTION AND ANALYSIS
Two review authors screened, independently assessed studies, and extracted data from the included studies. The clinical outcomes we examined were overall survival, response rate, progression-free survival, neurotoxicity, neutropenia, alopecia, and quality of life. We performed statistical analyses using fixed-effect and random-effects models following standard Cochrane methodology. We rated the certainty of evidence according to the GRADE approach.
MAIN RESULTS
Our literature search yielded 1500 records of 1466 studies; no additional studies were identified by searching grey literature or handsearching. We uploaded the search results into Covidence. After the exclusion of 92 duplicates, we screened titles and abstracts of 1374 records. Of these, we identified 24 studies for full-text screening. We included four parallel-group randomised controlled trials (RCTs). All trials were multicentred and conducted in a hospital setting. The studies included 981 eligible participants with recurrent epithelial ovarian cancer, tubal or primary peritoneal cancer with a median age ranging between 56 to 62 years of age. All participants had a WHO (World Health Organization) performance status of between 0 to 2. The proportion of participants with serous histology ranged between 56% to 85%. Participants included women who had platinum-sensitive (71%) and platinum-resistant (29%) relapse. Some participants were taxane pre-treated (5.6%), whilst the majority were taxane-naive (94.4%). No studies were classified as having a high risk of bias for any of the domains in the Cochrane risk of bias tool. We found that there may be little or no difference in overall survival (OS) between weekly paclitaxel and three-weekly paclitaxel, but the evidence is very uncertain (risk ratio (RR) of 0.94, 95% confidence interval (CI) 0.66 to 1.33, two studies, 263 participants, very low-certainty evidence). Similarly, there may be little or no difference in response rate (RR of 1.07, 95% CI 0.78 to 1.48, two studies, 263 participants, very low-certainty evidence) and progression-free survival (PFS) (RR of 0.83, 95% CI 0.46 to 1.52, two studies, 263 participants, very low-certainty evidence) between weekly and three-weekly paclitaxel, but the evidence is very uncertain. We found differences in the chemotherapy-associated adverse events between the weekly and three-weekly paclitaxel regimens. The weekly paclitaxel regimen may result in a reduction in neutropenia (RR 0.51, 95% 0.27 to 0.95, two studies, 260 participants, low-certainty evidence) and alopecia (RR 0.58, 95% CI 0.46 to 0.73, one study, 205 participants, low-certainty evidence). There may be little or no difference in neurotoxicity, but the evidence was very low-certainty and we cannot exclude an effect (RR 0.53, 95% CI 0.19 to 1.45, two studies, 260 participants). When examining the effect of paclitaxel dosage in the three-weekly regimen, the 250 mg/m paclitaxel regimen probably causes more neurotoxicity compared to the 175 mg/m regimen (RR 0.41, 95% CI 0.21 to 0.80, one study, 330 participants, moderate-certainty evidence). Quality-of-life data were not extractable from any of the included studies.
AUTHORS' CONCLUSIONS
Fewer people may experience neutropenia when given weekly rather than three-weekly paclitaxel (low-certainty evidence), although it may make little or no difference to the risk of developing neurotoxicity (very low-certainty evidence). This is based on the participants receiving lower doses of drug more often. However, our confidence in this result is low and the true effect may be substantially different from the estimate of the effect. Weekly paclitaxel probably reduces the risk of alopecia, although the rates in both arms were high (46% versus 79%) (low-certainty evidence). A change to weekly from three-weekly chemotherapy could be considered to reduce the likelihood of toxicity, as it may have little or no negative impact on response rate (very low-certainty evidence), PFS (very low-certainty evidence) or OS (very low-certainty evidence). Three-weekly paclitaxel, given at a dose of 175 mg/m compared to a higher dose,probably reduces the risk of neurotoxicity.We are moderately confident in this result; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. A change to 175 mg/m paclitaxel (from a higher dose), if a three-weekly regimen is used, probably has little or no negative impact on PFS or OS (very low-certainty evidence).
Topics: Adult; Alopecia; Bridged-Ring Compounds; Carcinoma, Ovarian Epithelial; Female; Humans; Middle Aged; Neoplasm Recurrence, Local; Neutropenia; Ovarian Neoplasms; Paclitaxel; Taxoids
PubMed: 35866378
DOI: 10.1002/14651858.CD008766.pub3 -
Biomedicine & Pharmacotherapy =... Dec 2021Combination therapy between paclitaxel (PTX) and doxorubicin (DXR) is applied as the first-line treatment of breast cancer. Co-administration of drugs at synergistic... (Comparative Study)
Comparative Study
Combination therapy between paclitaxel (PTX) and doxorubicin (DXR) is applied as the first-line treatment of breast cancer. Co-administration of drugs at synergistic ratio for treatment is facilitated with the use of nanocarriers, such as liposomes. However, despite the high response rate of solid tumors to this combination, a synergism of cardiotoxicity may limit the use. Thus, the objective of this work was to investigate the toxicity of long-circulating and fusogenic liposomes co-encapsulating PTX and DXR at the synergistic molar ratio (1:10) (LCFL-PTX/DXR). For this, clinical chemistry, histopathological analysis and electrocardiographic exams were performed on female Balb/c mice that received a single intravenous dose of LCFL-PTX/DXR. The results of the study indicated that the LD50 dose range (lethal dose for 50% of animals) of the LCFL-PTX/DXR treatment (28.9-34.7 mg/kg) is much higher than that found for free PTX/DXR treatment (20.8-23.1 mg/kg). In addition, liposomes promoted cardiac protection by not raising CK-MB levels in animals, keeping cardiomyocytes without injury or electrocardiographic changes. After 14 days of treatment, free PTX/DXR caused prolongation of the QRS interval when compared to LCFL-PTX/DXR treatment at the same dose (37.0 ± 5.01 ms and 30.83 ± 2.62 ms, respectively, with p = 0.017). The survival rate of animals treated with LCFL-PTX/DXR was three times higher than that of those treated with free drugs. Thus, it was established that the toxicity of LCFL-PTX/DXR is reduced compared to the combination of free PTX/DXR and this platform has advantages for the clinical treatment of breast cancer.
Topics: Action Potentials; Administration, Intravenous; Animals; Antineoplastic Combined Chemotherapy Protocols; Cardiotoxicity; Doxorubicin; Drug Compounding; Drug Synergism; Electrocardiography; Female; Heart Diseases; Lethal Dose 50; Lipids; Liposomes; Mice, Inbred BALB C; Myocytes, Cardiac; Paclitaxel; Mice
PubMed: 34653762
DOI: 10.1016/j.biopha.2021.112307