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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 -
American Journal of Hospital Pharmacy Nov 1979The stability of refrigerated and frozen solutions of doxorubicin hydrochloride was studied. Vials of doxorubicin hydrochloride with lactose (Adriamycin) were...
The stability of refrigerated and frozen solutions of doxorubicin hydrochloride was studied. Vials of doxorubicin hydrochloride with lactose (Adriamycin) were reconstituted with Sterile Water for Injection, USP, to provide a drug concentration of 2 mg/ml. Samples were refrigerated (4 C) for up to one year and frozen (-20C) for 30 days then assayed by high-performance liquid chromatography. One sample was assayed then refrozen each test period. Refrigerated and frozen samples showed no substantial loss of potency after six months and one month of storage, respectively. Filtration through a 0.22-micron filter did not affect potency. Degradation products were not detected, except for an unidentified small peak detected in the sample refrigerated for one year. Doxorubicin hydrochloride, when reconstituted with sterile water for injection, may be refrigerated for six months or frozen for one month without loss of potency.
Topics: Doxorubicin; Drug Stability; Drug Storage; Freezing; Refrigeration; Time Factors
PubMed: 517541
DOI: No ID Found -
International Journal of Molecular... Feb 2022In this study, actively-targeted (CD44-receptors) and dual stimuli (pH/redox)-responsive lipid-polymer nanoparticles were proposed as a delivery vehicle of doxorubicin...
In this study, actively-targeted (CD44-receptors) and dual stimuli (pH/redox)-responsive lipid-polymer nanoparticles were proposed as a delivery vehicle of doxorubicin hydrochloride in triple negative breast cancer cell lines. A phosphatidylcholine lipid film was hydrated with a solution of oxidized hyaluronic acid and doxorubicin, chosen as model drug, followed by a crosslinking reaction with cystamine hydrochloride. The obtained spherical nanoparticles (mean diameter of 30 nm) were found to be efficiently internalized in cancer cells by a receptor-mediated endocytosis process, and to modulate the drug release depending on the pH and redox potential of the surrounding medium. In vitro cytotoxicity assays demonstrated the safety and efficacy of the nanoparticles in enhancing the cytotoxic effect of the free anticancer drug, with the IC values being reduced by two and three times in MDA-MB-468 and MDA-MB-231, respectively. The combination of self-assembled phospholipid molecules with a polysaccharide counterpart acting as receptor ligand, and stimuli-responsive chemical moieties, was carried out on smart multifunctional nanoparticles able to actively target breast cancer cells and improve the in vitro anticancer activity of doxorubicin.
Topics: Antineoplastic Agents; Breast Neoplasms; Cell Line, Tumor; Doxorubicin; Drug Delivery Systems; Drug Liberation; Endocytosis; Female; Humans; Hyaluronan Receptors; Hyaluronic Acid; Hydrogen-Ion Concentration; Lipids; Liposomes; Nanoparticles; Particle Size; Polysaccharides
PubMed: 35216501
DOI: 10.3390/ijms23042386 -
Pharmacological Research Nov 2022Acute myeloid leukemia (AML) is featured with poor prognosis and high mortality, because chemo-resistance, nonspecific distribution and dose-limiting toxicity lead to a...
Acute myeloid leukemia (AML) is featured with poor prognosis and high mortality, because chemo-resistance, nonspecific distribution and dose-limiting toxicity lead to a high rate of relapse and a very low 5-year survival percentage of less than 25%. CXCR4 is a highly expressed chemokine receptor in multiple types of AML cells and closely associated with the drug resistance and relapse. In this work, we integrate a chemically synthesized CXCR4 antagonistic peptide and doxorubicin using DSPE-mPEG2000 micelles (referred to as M-E5-Dox) that is applied to a very challenging refractory AML mouse model as well as human AML cell lines. Results showed that M-E5-Dox can effectively bind to the CXCR4-expressing AML cells, downregulating the signaling proteins mediated by CXCR4/CXCL12 axis and increasing the cellular uptake of Dox. Importantly, M-E5-Dox remarkably decreases the leukemic cells in the peripheral blood and bone marrow, as well as their infiltration in the spleen and liver of the AML mice, which in turn prolongs the survival significantly. Meanwhile, M-E5-Dox did not increase the cardiotoxicity of Dox. In conclusion, M-E5-Dox harnesses the functions of CXCR4 specific binding and CXCR4 antagonism of the peptide and the tumor cell killing capacity of Dox, which displays significant therapeutic effects and promising translational potentials for the treatment of refractory AML.
Topics: Humans; Mice; Animals; Leukemia, Myeloid, Acute; Doxorubicin; Signal Transduction; Peptides; Recurrence; Receptors, CXCR4
PubMed: 36241000
DOI: 10.1016/j.phrs.2022.106503 -
Drug Development and Industrial Pharmacy Nov 2013In this study, we propose a new solution for the nanoencapsulation of hydrophilic anticancer drug, doxorubicin hydrochloride (DOX). The drug molecules are solubilized in... (Comparative Study)
Comparative Study
In this study, we propose a new solution for the nanoencapsulation of hydrophilic anticancer drug, doxorubicin hydrochloride (DOX). The drug molecules are solubilized in the core of aqueous nanoreservoirs, so-called aqueous core nanocapsules (ACN) recently developed by our team, and dispersed in aqueous bulk media. Since it is well acknowledged that the nanoencapsulation of DOX has many advantages, like reducing the sides effects (e.g. cardiac toxicity), we propose through the present study a novel formulation solution for this purpose. After focusing on the formulation process for optimizing the drug encapsulation yield, the DOX-release profiles were followed up and analyzed. Different physicochemical and in vitro characterization were performed, and complement activation experiments. ACN were shown efficient to encapsulate DOX reaching yields as high as 80%, followed by a sustained release governed by a diffusion-controlled mechanism. The loaded nanocarriers showed low levels of complement activation, compatible with stealth properties. To summarize, this study brings out a new tool for the nanoencapsulation of hydrophilic anticancers and could open new doors for the administration of this particular class of drugs.
Topics: Antibiotics, Antineoplastic; Chemical Phenomena; Complement Activation; Delayed-Action Preparations; Diffusion; Doxorubicin; Drug Compounding; Drug Delivery Systems; Drug Stability; Emulsions; Humans; Hydrophobic and Hydrophilic Interactions; Kinetics; Mineral Oil; Nanocapsules; Particle Size; Pentanes; Pharmaceutical Vehicles; Polyethylene Glycols; Solubility; Surface Properties; Surface-Active Agents
PubMed: 23289391
DOI: 10.3109/03639045.2012.730526 -
European Journal of Pharmaceutics and... Sep 2008The release behavior of a water-soluble small molecule drug from the drug-loaded nanofibers prepared by emulsion-electrospinning was investigated. Doxorubicin...
The release behavior of a water-soluble small molecule drug from the drug-loaded nanofibers prepared by emulsion-electrospinning was investigated. Doxorubicin hydrochloride (Dox), a water-soluble anticancer agent, was used as the model drug. The laser scanning confocal microscopic images indicated that the drug was well incorporated into amphiphilic poly(ethylene glycol)-poly(L-lactic acid) (PEG-PLA) diblock copolymer nanofibers, forming "core-sheath" structured drug-loaded nanofibers. The drug release behavior of this drug-loaded system showed a three-stage diffusion-controlled mechanism, in which the release rate of the first stage was slower than that of the second stage, but both obeyed Fick's second law. Based on these results, it is concluded that the Dox-loaded fibers prepared by emulsion-electrospinning represent a reservoir-type delivery system in which the Dox release rate decreases with the increasing Dox content in the fibers.
Topics: Antibiotics, Antineoplastic; Chemistry, Pharmaceutical; Delayed-Action Preparations; Diffusion; Doxorubicin; Drug Carriers; Drug Compounding; Emulsions; Kinetics; Lactates; Models, Chemical; Nanostructures; Polyethylene Glycols; Solubility; Surface Properties; Technology, Pharmaceutical
PubMed: 18472256
DOI: 10.1016/j.ejpb.2008.03.010 -
ACS Applied Materials & Interfaces Jun 2017Conventional organic and inorganic drug nanocarriers suffer from serious drawbacks such as low drug-storage capacity and uncontrolled release. Moreover, multidrug...
Rational Design of Metal Organic Framework Nanocarrier-Based Codelivery System of Doxorubicin Hydrochloride/Verapamil Hydrochloride for Overcoming Multidrug Resistance with Efficient Targeted Cancer Therapy.
Conventional organic and inorganic drug nanocarriers suffer from serious drawbacks such as low drug-storage capacity and uncontrolled release. Moreover, multidrug resistance (MDR) has been one of the primary causes leading to chemotherapy failure for cancers. The main reason for MDR is the overexpressed active efflux transporters such as P-glycoprotein. Here, zeolitic imidazolate framework ZIF-8, as one of the biocompatible metal organic frameworks (MOFs), is reported for the first time as the multidrug carrier to realizing the efficient codelivery of verapamil hydrochloride (VER) as the P-glycoprotein inhibitor as well as doxorubicin hydrochloride (DOX) as an anticancer drug to overcome the MDR in addition to realize the active targeted ability for an efficient anticancer effect. Uniform ZIF-8 nanoparticles encapsulating DOX and VER are achieved by a facile one-pot process, in which the VER is used to overcome the multidrug resistance. Furthermore, methoxy poly(ethylene glycol)-folate (PEG-FA) is used to stabilize the (DOX+VER)@ZIF-8 to realize prolonged circulations and an active targeting drug delivery. In particular, the ZIF-8 exhibits high drug loading content up to ∼40.9% with a pH-triggered release behavior. Importantly, the PEG-FA/(DOX+VER)@ZIF-8 shows enhanced therapeutic efficiencies with much safety compared with the direct administration of free DOX both in vitro and in vivo. Near infrared fluorescent (NIRF) imaging indicates that the PEG-FA/(DOX+VER)@ZIF-8 can increase the drug accumulations in tumors for targeted cancer therapy. Therefore, the PEG-FA/(DOX+VER)@ZIF-8 multidrug delivery system can be used as a promising efficient formulation in reversing the multidrug resistance for targeted cancer therapy.
Topics: Doxorubicin; Drug Resistance, Multiple; Humans; Metal-Organic Frameworks; Neoplasms; Verapamil
PubMed: 28530401
DOI: 10.1021/acsami.7b05142 -
International Journal of Nanomedicine 2021Glioblastoma multiforme (GBM) poorly responds to chemotherapy owing to the existence of blood-brain barriers (BBB). It has been a long desire to develop BBB-permeable...
PURPOSE
Glioblastoma multiforme (GBM) poorly responds to chemotherapy owing to the existence of blood-brain barriers (BBB). It has been a long desire to develop BBB-permeable vehicles to facilitate drug targeting to GBM.
METHOD AND RESULTS
Here, we report that doxorubicin hydrochloride loaded in ApoE peptide-functionalized reduction-sensitive polymersomes (ApoE-PS-DOX) induces potent therapy of orthotopic U-87 MG model in nude mice. ApoE-PS-DOX with varying amount of ApoE (10~30 mol%) all had stable DOX loading and small sizes (< 90 nm). As revealed by flow cytometry, confocal microscopy, apoptosis and MTT assays, ApoE-PS-DOX with 20 mol.% ApoE induced the best cellular uptake and inhibitory effect to U-87 MG cells, which were much better than the non-targeted PS-DOX and liposomal doxorubicin (Lipo-DOX) used in the clinic. ApoE-PS-DOX revealed a pharmacokinetic profile comparable to PS-DOX but induced considerably better growth inhibition of orthotopically xenografted U-87 MG tumors in nude mice than PS-DOX and Lipo-DOX, leading to significant survival benefits with a median survival time of 44 days, which was almost doubled relative to the phosphate-buffered saline (PBS) group. Moreover, in contrast to mice treated with Lipo-DOX and PS-DOX, ApoE-PS-DOX group exhibited little body weight loss, signifying that ApoE-PS-DOX not only has low side effects but also can effectively inhibit glioblastoma invasion.
CONCLUSION
This ApoE-docked multifunctional polymersomal doxorubicin induces potent and safe chemotherapy of orthotopic U-87 MG model in nude mice offering an alternative treatment modality for GBM.
Topics: Animals; Apolipoproteins E; Blood-Brain Barrier; Cell Line, Tumor; Cell Transformation, Neoplastic; Doxorubicin; Drug Carriers; Glioblastoma; Humans; Mice; Mice, Nude; Oxidation-Reduction; Polymers
PubMed: 34163162
DOI: 10.2147/IJN.S314895 -
Pediatric Blood & Cancer Aug 2004
Clinical Trial
Topics: Adolescent; Antibiotics, Antineoplastic; Child, Preschool; Doxorubicin; Female; Humans; Male; Polyethylene Glycols; Sarcoma; Treatment Outcome
PubMed: 15236282
DOI: 10.1002/pbc.20029 -
International Journal of Pharmaceutics Nov 2016Novel enoxaparin sodium-PLGA hybrid nanocarries (EPNs) were successfully designed for sustained delivery of hydrophilic cationic doxorubicin hydrochloride (DOX) and to...
Novel enoxaparin sodium-PLGA hybrid nanocarries (EPNs) were successfully designed for sustained delivery of hydrophilic cationic doxorubicin hydrochloride (DOX) and to overcome multidrug resistance (MDR). By incorporation of the negative polymer of enoxaparin sodium (ES), DOX was highly encapsulated into EPNs with an encapsulation efficiency of 92.49%, and ES effectively inhibited the proliferation of HUVEC cell lines. The in vivo pharmacokinetics study after intravenous injection indicated that DOX-loaded EPNs (DOX-EPNs) exhibited a higher area under the curve (AUC) and a longer half-life (t) in comparison with DOX solution (DOX-Sol). The biodistribution study demonstrated that DOX-EPNs increased the DOX level in plasma and decreased the accumulation of DOX in liver and spleen. Compared with DOX-Sol, DOX-EPNs increased the cytotoxicity in P-gp over-expressing MCF-7/Adr cells, attributed to the higher intracellular efficiency of DOX produced by the EPNs. DOX-EPNs entered into resistant tumor cells by multiple endocytosis pathways, which resulted in overcoming the multidrug resistance of MCF-7/Adr cells by escaping the efflux induced by P-gp transporters.
Topics: Animals; Antineoplastic Agents; Caco-2 Cells; Cell Proliferation; Cell Survival; Doxorubicin; Drug Carriers; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Endocytosis; Enoxaparin; Human Umbilical Vein Endothelial Cells; Humans; Lactic Acid; MCF-7 Cells; Mice; Nanostructures; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Rats; Rats, Sprague-Dawley
PubMed: 27628785
DOI: 10.1016/j.ijpharm.2016.09.037