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Journal of Clinical Pharmacy and... Dec 2019The etoposide, doxorubicin hydrochloride, vincristine sulphate, cyclophosphamide and prednisone (EPOCH) chemotherapy regimen is effective in patients with relapsed or...
WHAT IS KNOWN AND OBJECTIVES
The etoposide, doxorubicin hydrochloride, vincristine sulphate, cyclophosphamide and prednisone (EPOCH) chemotherapy regimen is effective in patients with relapsed or refractory non-Hodgkin's lymphoma. However, vincristine and doxorubicin hydrochloride are relatively toxic, leading to neurovirulence and cardiotoxicity, respectively. In this study, we replaced these drugs with vindesine and epirubicin hydrochloride to reduce the cardiotoxicity and evaluated admixtures containing these drugs along with etoposide in a single infusion bag in vitro.
METHODS
The appearance and pH of the admixtures were evaluated, and the number of particles was detected. High-performance liquid chromatography was used to measure the concentration and degradation rates of etoposide, epirubicin hydrochloride and vindesine sulphate in each admixture.
RESULTS AND DISCUSSION
No precipitation occurred when mixing clinically relevant concentrations of etoposide, epirubicin hydrochloride and vindesine sulphate in a 0.9% NaCl injection solution. Furthermore, the delta pH of the admixtures was ≤0.12 throughout the experiment, and the number of particles (≥10 and ≥25 μm) in the solutions over the 24 hours post-preparation period met USP standards. Etoposide, epirubicin hydrochloride and vindesine sulphate were retained at >96% of their initial concentrations in the admixtures at 25°C over the course of the experiment. Etoposide, epirubicin hydrochloride and vindesine sulphate are compatible when mixed in a 0.9% NaCl injection solution, and the admixtures are stable for at least 24 hours when stored in infusion bags.
WHAT IS NEW AND CONCLUSION
This in vitro analysis indicates the suitability of our novel admixtures containing less toxic drug equivalents in a single infusion bag for clinical application.
Topics: Cyclophosphamide; Doxorubicin; Drug Stability; Epirubicin; Etoposide; Humans; Infusion Pumps; Lymphoma, Non-Hodgkin; Prednisone; Vincristine; Vindesine
PubMed: 31529525
DOI: 10.1111/jcpt.13007 -
International Journal of Nanomedicine 2020Synergistic treatment integrating photothermal therapy (PTT) and chemotherapy is a promising strategy for hepatocellular carcinoma (HCC). However, the most commonly used...
INTRODUCTION
Synergistic treatment integrating photothermal therapy (PTT) and chemotherapy is a promising strategy for hepatocellular carcinoma (HCC). However, the most commonly used photothermal agent, IR820, and chemotherapeutic drug, doxorubicin hydrochloride (DOX), are both hydrophilic molecules that suffer from the drawbacks of a short circulation time, rapid elimination and off-target effects.
METHODS AND RESULTS
Herein, a novel nanodrug that combined HCC-targeted IR820 and DOX was developed based on excipient-free co-assembly. First, lactosylated IR820 (LA-IR820) was designed to target HCC. Then, the LA-IR820/DOX nanodrug (LA-IR820/DOX ND) was purely self-assembled without excipient assistance. The physicochemical properties and the chemo-photothermal antitumour activity of the excipient-free LA-IR820/DOX ND were evaluated. More importantly, the obtained LA-IR820/DOX ND exhibited 100% drug loading, remarkable HCC targeting and excellent antitumour efficacy.
CONCLUSION
This excipient-free LA-IR820/DOX ND may be a promising candidate for the synchronous delivery and synergistic targeting of IR820 and DOX as a combined chemo-photothermal therapy.
Topics: Animals; Antineoplastic Agents; Carcinoma, Hepatocellular; Cell Line, Tumor; Doxorubicin; Drug Delivery Systems; Drug Liberation; Drug Synergism; Humans; Indocyanine Green; Lactose; Liver Neoplasms; Mice; Nanoparticles
PubMed: 32606687
DOI: 10.2147/IJN.S247617 -
The Journal of Pharmacy and Pharmacology Apr 2020Zein nanoparticles (Zein NPs) were used as a hydroxyapatite (HA) biomineralization template to generate HA/Zein NPs. Doxorubicin hydrochloride (DOX) was loaded on...
OBJECTIVES
Zein nanoparticles (Zein NPs) were used as a hydroxyapatite (HA) biomineralization template to generate HA/Zein NPs. Doxorubicin hydrochloride (DOX) was loaded on HA/Zein NPs (HA/Zein-DOX NPs) to improve its pH-sensitive release, bioavailability and decrease cardiotoxicity.
METHODS
HA/Zein-DOX NPs were prepared by phase separation and biomimetic mineralization method. Particle size, polydispersity index (PDI), Zeta potential, transmission electron microscope, X-ray diffraction and Fourier-transform infrared spectroscopy of HA/Zein-DOX NPs were characterized. The nanoparticles were then evaluated in vitro and in vivo.
KEY FINDINGS
The small PDI and high Zeta potential demonstrated that HA/Zein-DOX NPs were a stable and homogeneous dispersed system and that HA was mineralized on Zein-DOX NPs. HA/Zein-DOX NPs showed pH-sensitive release. Compared with free DOX, HA/Zein-DOX NPs increased cellular uptake which caused 7 times higher in-vitro cytotoxicity in 4T1 cells. Pharmacokinetic experiments indicated the t and AUC of HA/Zein-DOX NPs were 2.73- and 3.12-fold higher than those of DOX solution, respectively. Tissue distribution exhibited HA/Zein-DOX NPs reduced heart toxicity with lower heart targeting efficiency (18.58%) than that of DOX solution (37.62%).
CONCLUSION
In this study, HA/Zein-DOX NPs represented an antitumour drug delivery system for DOX in clinical tumour therapy with improved bioavailability and decreased cardiotoxicity.
Topics: Animals; Biological Availability; Cell Line; Cell Survival; Doxorubicin; Drug Carriers; Drug Delivery Systems; Drug Liberation; Durapatite; Mice; Nanoparticles; Rats; Rats, Sprague-Dawley; Tissue Distribution; Zein
PubMed: 31975457
DOI: 10.1111/jphp.13223 -
International Journal of Pharmaceutics May 2024Doxorubicin hydrochloride (DOX) is an anticancer agent used in cancer chemotherapy. The purpose of this study was to design nanostructured lipid carriers (NLCs) of DOX...
Doxorubicin hydrochloride (DOX) is an anticancer agent used in cancer chemotherapy. The purpose of this study was to design nanostructured lipid carriers (NLCs) of DOX as smart chemotherapy to improve its photostability and anticancer efficacy. The characteristics of DOX and DOX-loaded NLCs were investigated using UV-Vis spectroscopy, Fourier transform infrared (FTIR) spectroscopy, particle size, and zeta potential study. The cytotoxicity of DOX was evaluated against three cancer cell lines (HeLa, A549, and CT-26). The particle size and zeta potential were in the range 58.45-94.08 nm and -5.80 mV - -18.27 mV, respectively. The chemical interactions, particularly hydrogen bonding and van der Waals forces, between DOX and the main components of NLCs was confirmed by FTIR. NLCs showed the sustained release profile of DOX. The photostability results revealed that the NLC system improved the photostability of DOX. Cytotoxicity results using the three cell lines showed that all formulations improved the anticancer efficacy of free DOX, and the efficacy was dependent on cell type and particle size. These results suggest that DOX-loaded NLCs are promising chemotherapeutic agents for cancer treatment.
Topics: Doxorubicin; Humans; Drug Carriers; Nanoparticles; Lipids; Cell Line, Tumor; Particle Size; Drug Liberation; Cell Survival; Antibiotics, Antineoplastic; Nanostructures; Drug Stability; HeLa Cells; A549 Cells; Antineoplastic Agents
PubMed: 38537925
DOI: 10.1016/j.ijpharm.2024.124048 -
Carbohydrate Polymers Feb 2016A doxorubicin conjugated prodrug incorporated acid-sensitive linkage between drug and Pluronic F127-chitosan (F127-CS) polymer was successfully synthesized. Subsequently...
A doxorubicin conjugated prodrug incorporated acid-sensitive linkage between drug and Pluronic F127-chitosan (F127-CS) polymer was successfully synthesized. Subsequently a pH-sensitive polymeric micelle system was designed based on the conjugated prodrugs (F127-CS-DOX) to co-deliver doxorubicin and paclitaxel. Paclitaxel (PTX) was physically entrapped in the hydrophobic inner core of the micelles simultaneously. The structures of conjugates were analyzed by means of (1)H NMR and UV-vis spectrum. Size distribution and morphology of the micelles were observed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The results indicated that obtained micelles had good dispersity and the diameter was between 56.3 and 403.4 nm. The loading of PTX into the micelle increased with higher DOX content. DOX and PTX release from polymeric micelles followed an acid-triggered manner. Furthermore, in vivo pharmacokinetic study also showed that the area under the plasma concentration time curve (AUC0-∞) values of PTX and DOX for PTX-loaded F127-CS-DOX micelles in rats were 3.97 and 4.38-fold higher than those for PTX plus DOX solution. These results suggested the PTX-loaded F127-CS-DOX micelles would be a promising carrier for co-delivering DOX and PTX.
Topics: Animals; Doxorubicin; Hydrogen-Ion Concentration; Magnetic Resonance Spectroscopy; Male; Micelles; Microscopy, Electron, Transmission; Paclitaxel; Polymers; Rats; Rats, Wistar; Spectroscopy, Fourier Transform Infrared
PubMed: 26686101
DOI: 10.1016/j.carbpol.2015.10.050 -
Journal of Biomaterials Science.... Feb 2023To achieve efficient delivery and precise release of chemotherapy drugs at tumor sites, an active targeting multi-responsive drug delivery platform was developed. Here,...
To achieve efficient delivery and precise release of chemotherapy drugs at tumor sites, an active targeting multi-responsive drug delivery platform was developed. Here, doxorubicin hydrochloride (DOX) was loaded onto polydopamine (PDA), which were coated by the cystamine-modified hyaluronic acid (HA-Cys), designated as DOX@PDA-HA (PDH). The combination of PDA and HA-Cys endowed the nanoplatform photothermal conversion, tumor-targeting, and pH/redox/NIR sensitive drug release capacity. Moreover, HA could be degraded by the excess hyaluronidase (HAase) in the tumor microenvironment (TME), promoting DOX release, and further enhancing the effect of chemotherapy. Experimental results demonstrated PDH good biocompatibility, high loading rate, targeted drug delivery, and efficient tumor cell killing ability. This ingenious strategy based on PDH showed huge potential in photothermal/chemotherapy combination treatment of cancer.
Topics: Humans; Neoplasms; Drug Delivery Systems; Doxorubicin; Nanoparticles; Cell Line, Tumor; Drug Liberation; Tumor Microenvironment
PubMed: 35943449
DOI: 10.1080/09205063.2022.2112310 -
International Journal of Pharmaceutics May 2017Analytical ultracentrifugation (AUC) is a powerful tool for the study of particle size distributions and interactions with high accuracy and resolution. In this work, we...
Analytical ultracentrifugation (AUC) is a powerful tool for the study of particle size distributions and interactions with high accuracy and resolution. In this work, we show how the analysis of sedimentation velocity data from the AUC can be used to characterize nanocarrier drug delivery systems used in nanomedicine. Nanocarrier size distribution and the ratio of free versus nanoparticle-encapsulated drug in a commercially available liposomal doxorubicin formulation are determined using interference and absorbance based AUC measurements and compared with results generated with conventional techniques. Additionally, the potential of AUC in measuring particle density and the detection of nanocarrier sub-populations is discussed as well. The unique capability of AUC in providing reliable data for size and composition in a single measurement and without complex sample preparation makes this characterization technique a promising tool both in nanomedicine product development and quality control.
Topics: Antibiotics, Antineoplastic; Doxorubicin; Nanomedicine; Particle Size; Polyethylene Glycols; Ultracentrifugation
PubMed: 28342788
DOI: 10.1016/j.ijpharm.2017.03.046 -
Carbohydrate Polymers Dec 2022High swelling hydrogel networks (HSHNs) are materials with the ability to high swelling and outstanding candidates for sustained drug delivery systems (DDSs). The...
High swelling hydrogel networks (HSHNs) are materials with the ability to high swelling and outstanding candidates for sustained drug delivery systems (DDSs). The present paper demonstrates three different chitosan nanohydrogel networks (CNHN I-III) prepared through covalent and non-covalent interactions. These hydrogels have a high swelling ratio (up to 38-fold their dry weight) in various conditions. Two types of these hydrogels (CNHN I and II), swelled rapidly in an acidic environment, were able to successfully load an extraordinary amount (up to 95 %) of a model drug doxorubicin hydrochloride (DOX.HCl) at a 1:1 ratio (wt./wt.). The CNHN III had substantial swelling in pH 7.4, with a loading capacity of 92 % 5-fluorouracil (5-FU) at a 1:1 ratio (wt./wt.). The CNHN I and II have been considered for systemic drug delivery, while the CNHN III is one of the best candidates for oral drug delivery.
Topics: Chitosan; Doxorubicin; Drug Carriers; Drug Delivery Systems; Drug Liberation; Fluorouracil; Hydrogels; Hydrogen-Ion Concentration
PubMed: 36241333
DOI: 10.1016/j.carbpol.2022.120143 -
International Journal of Biological... Sep 2018In the present study, the potential of doxorubicin hydrochloride (DOX)-loaded electrospun chitosan/cobalt ferrite/titanium oxide nanofibers was studied to investigate...
In the present study, the potential of doxorubicin hydrochloride (DOX)-loaded electrospun chitosan/cobalt ferrite/titanium oxide nanofibers was studied to investigate the simultaneous effect of hyperthermia and chemotherapy against melanoma cancer B16F10 cell lines. The cobalt ferrite nanoparticles were synthesized via microwave heating method. The titanium oxide nanoparticles were mixed with cobalt ferrite to control the temperature rise. The synthesized nanoparticles and nanofibers were characterized using X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), and vibrating sample magnetometer (VSM) analysis. The DOX loading efficiency and in vitro drug release of DOX from nanofibers were investigated at both physiological and acidic conditions by an alternating of magnetic field and without magnetic field effect. The fastest release of DOX from prepared magnetic nanofibers was observed at acidic pH by alternating of magnetic field. The antitumor activity of synthesized nanofibers was also investigated on the melanoma cancer B16F10 cell lines. The obtained results revealed that the DOX loaded-electrospun chitosan/cobalt ferrite/titanium oxide nanofibers can be used for localized cancer therapy.
Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Chitosan; Cobalt; Delayed-Action Preparations; Doxorubicin; Drug Liberation; Ferric Compounds; Magnetics; Melanoma, Experimental; Mice; Nanofibers; Nanoparticles; Temperature; Titanium
PubMed: 29723626
DOI: 10.1016/j.ijbiomac.2018.04.161 -
Journal of Nanoscience and... May 2021Hierarchical nanoparticles are of great interest because they possess unique physicochemical properties and multiple functionalities, providing a wealth of possibilities...
Hierarchical nanoparticles are of great interest because they possess unique physicochemical properties and multiple functionalities, providing a wealth of possibilities for various applications. In this work, we have developed a well-designed method to prepare hierarchical magnetic nanoparticles Fe₃O₄@mSiO₂@CS by integrating a solvothermal method for synthesizing the Fe₃O₄ core, a dualtemplating micelle system for preparing a layer of mesoporous silica (mSiO₂) shell, and a silane coupling method via -glycidoxypropyltrimethoxysilane for binding a chitosan (CS) layer on the silica surface. The porous hierarchical nanoparticles were characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), dynamic light scattering nanoparticle size analyzer, and specific surface area and pore size analyzer. The loading capacity and the release behavior of the as-prepared nanoparticles for doxorubicin hydrochloride were studied, and it was found that the drug release rate was faster at pH 6.0 than at pH 7.4, revealing the pH-responsive property of the nanoparticles.
Topics: Chitosan; Doxorubicin; Drug Carriers; Drug Delivery Systems; Drug Liberation; Hydrogen-Ion Concentration; Nanoparticles; Silicon Dioxide; Spectroscopy, Fourier Transform Infrared
PubMed: 33653475
DOI: 10.1166/jnn.2021.19154