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The Journal of Physical Chemistry. B Nov 2023For the design of an efficient drug delivery system utilizing an ionic liquid (IL) as a carrier, it is prudent to gain molecular/atomistic level insights of a drug with...
Comprehensive NMR Investigation of Imidazolium-Based Ionic Liquids [BMIM][OSU] and [BMIM][Cl] Impact on Binding and Dynamics of the Anticancer Drug Doxorubicin Hydrochloride.
For the design of an efficient drug delivery system utilizing an ionic liquid (IL) as a carrier, it is prudent to gain molecular/atomistic level insights of a drug with IL in terms of binding and dynamics. In this scenario, the influence of anionic counterpart of imidazolium-based ILs, namely, 1-butyl-3-methyl-imidazolium octyl sulfate [BMIM][OSU] and 1-butyl-3-methyl-imidazolium chloride [BMIM][Cl] in their submicellar region ([IL] = 20 mM) on the model water-soluble anticancer drug doxorubicin hydrochloride (DOX) was probed by employing an arsenal of nuclear magnetic resonance (NMR) approaches. The salient feature of the present study includes the significant interaction of DOX with [BMIM][OSU], whereas the lack of such an interaction with [BMIM][Cl] is gauged by H NMR translation self-diffusometry and is further corroborated by C chemical shift perturbation. The two-step model was utilized to estimate the bound fraction (p) and equivalent partition coefficient () of DOX with [BMIM][OSU]. A combination of selective and nonselective spin-lattice relaxation rates ( and , respectively) enables to gauze the significant interaction of DOX with [BMIM][OSU] over [BMIM][Cl]. Furthermore, 1D transient and truncated driven nuclear Overhauser enhancement (NOE) data analyses in the initial rate limit permits the evaluation of the cross-relaxation efficacy of DOX with the investigated ILs. An Arrhenius-type temperature dependence of the drug's self-diffusion was observed for DOX, DOX-[BMIM][OSU], and DOX-[BMIM][Cl] aqueous mixtures and the corresponding activation energies were evaluated.
Topics: Ionic Liquids; Doxorubicin; Magnetic Resonance Spectroscopy; Magnetic Resonance Imaging; Water; Antineoplastic Agents
PubMed: 37975332
DOI: 10.1021/acs.jpcb.3c06036 -
Journal of Drug Targeting May 2013High-density lipoprotein (HDL) particles can deliver cholesterol from peripheral tissues to the liver through apolipoprotein A1 (Apo A1), which specifically binds to the...
High-density lipoprotein (HDL) particles can deliver cholesterol from peripheral tissues to the liver through apolipoprotein A1 (Apo A1), which specifically binds to the scavenger receptor class B type 1 (SR-B1) receptor on the surface of hepatocytes. Therefore, ApoA1 can be potentially used to target drugs to the liver. In this study, we successfully loaded doxorubicin hydrochloride (Dox or Dox-HCl), which is a hydrophilic drug used in a wide variety of clinical applications, into the core of reconstituted HDL (rHDL prepared by apoAI and egg phospholipids) to form a doxorubicin-HDL complex (rHDL-Dox). The MTT assays showed that rHDL-Dox particles also had higher cytotoxicity against several cells lines compared to free drug or Dox encapsulated into liposomes. A cellular uptake assay demonstrated that rHDL-Dox had higher absorption in SR-BI receptor positive liver cells. Importantly, in vivo experiments showed that rHDL-Dox can reduce tumor growth more effectively than liposomes. In addition, an in vitro hemolysis assay showed that rHDL-Dox caused only limited hemolysis in the case of high doses. Taken together, our findings indicate that rHDL is a safe and effective drug delivery system for targeting liver.
Topics: Animals; Antibiotics, Antineoplastic; Apolipoprotein A-I; Carrier Proteins; Cell Line, Tumor; Doxorubicin; Drug Carriers; Drug Delivery Systems; Hep G2 Cells; Humans; Hydrophobic and Hydrophilic Interactions; Lipoproteins, HDL; Liposomes; Liver; Male; Mice; Mice, Inbred BALB C; Mice, Nude
PubMed: 23600747
DOI: 10.3109/1061186X.2012.757769 -
Urology Nov 1976The suggested activity of doxorubicin hydrochloride (Adriamycin), cyclophosphamide, and 5-fluorouracil as single agents in the treatment of advanced prostate and/or...
The suggested activity of doxorubicin hydrochloride (Adriamycin), cyclophosphamide, and 5-fluorouracil as single agents in the treatment of advanced prostate and/or transitional cell carcinoma led us to examine the response to these drugs used in combination. Combination chemotherapy has the theoretical advantages of additive antitumor effect without additive toxicity to the host. One of 8 patients with Stage D, endocrine unresponsive prostatic adenocarcinoma achieved an objective response. There were five stable and one subjective responses. Only 1 patient showed progression during the initial six-week trial. Two of 3 patients with transitional cell carcinoma had an objective response. This three-drug combination was well tolerated by elderly patients and on the basis of this small series further trials are warranted.
Topics: Acid Phosphatase; Adenocarcinoma; Aged; Carcinoma, Transitional Cell; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Fluorouracil; Humans; Kidney Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Metastasis; Prostatic Neoplasms; Urinary Bladder Neoplasms
PubMed: 982733
DOI: 10.1016/0090-4295(76)90275-2 -
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi =... Mar 2022Objective To investigate the possible mechanism of doxorubicin hydrochloride (DOX) inhibiting the proliferation of HT29 and HCT15 colon cancer cells. Methods The...
Objective To investigate the possible mechanism of doxorubicin hydrochloride (DOX) inhibiting the proliferation of HT29 and HCT15 colon cancer cells. Methods The gradient concentrations of (0, 0.08, 0.16, 0.32, 0.64, 1.28) μmol/L DOX were used to treat HT29 and HCT15 cells for 24, 48 and 72 hours, and the cell proliferation activity was detected by CCK-8 assay to determine the optimal DOX concentration and treatment time. According to different treatments, HT29 and HCT15 cells were divided into 2 groups: control group (only DMSO treatment) and (0.16, 0.32, 0.64, 1.28) μmol/L DOX group. Western blot was used to detect the effect of inhibiting autophagy on apoptosis, with 3-methyladenine (3-MA) group and 3-MA combined with DOX group supplemented. The colony formation of colon cancer cells was detected by colony formation assay, and the expression of cell B-cell lymphoma 2 (Bcl2), Bcl2-associated X protein (BAX), beclin 1, and LC3 protein were detected by Western blot. Results DOX inhibited the proliferation and colony formation of colon cancer cells, and promoted cell apoptosis in a concentration-dependent manner; DOX promoted autophagy in cells, and the expression of beclin 1 and LC3 II increased in a concentration-dependent manner; DOX promoted apoptosis of colon cancer cells, which was improved by inhibiting autophagy. Conclusion DOX inhibits the proliferation of colon cancer cells and promotes their apoptosis, and inhibition of autophagy in colon cancer cells can increase the sensitivity of apoptosis induced by DOX.
Topics: Apoptosis; Autophagy; Cell Line, Tumor; Colonic Neoplasms; Doxorubicin; Humans
PubMed: 35365989
DOI: No ID Found -
Carbohydrate Polymers Oct 2016Chondroitin-4-sulfate (CS), a glycosaminoglycan, was used to prepare CS-capped super-paramagnetic iron oxide nanoparticles, which were further employed for loading a...
Chondroitin-4-sulfate (CS), a glycosaminoglycan, was used to prepare CS-capped super-paramagnetic iron oxide nanoparticles, which were further employed for loading a water-soluble chemotherapeutic agent (doxorubicin hydrochloride, DOX). CS-capped SPIONs have potential biomedical application in cancer targeting. The optimized formulation had a hydrodynamic size of 91.2±0.8nm (PDI; 0.228±0.004) and zeta potential of -49.1±1.66mV. DOX was loaded onto the formulation up to 2% (w/w) by physical interaction with CS. TEM showed nano-sized particles having a core-shell structure. XRD confirmed crystal phase of iron oxide. FT-IR conceived the interaction of iron oxide with CS as bidentate chelation and also confirmed DOX loading. Vibration sample magnetometry confirmed super-paramagnetic nature of nanoparticles, with saturation magnetization of 0.238emug(-1). In vitro release profile at pH 7.4 showed that 96.67% of DOX was released within 24h (first order kinetics). MTT assay in MCF7 cells showed significantly higher (p<0.0001) cytotoxicity for DOX in SPIONs than DOX solution (IC50 values 6.294±0.4169 and 11.316±0.1102μgmL(-1), respectively).
Topics: Antineoplastic Agents; Cell Survival; Chondroitin Sulfates; Doxorubicin; Drug Carriers; Drug Liberation; Humans; MCF-7 Cells; Magnetite Nanoparticles; Microscopy, Electron, Transmission; Particle Size; Spectroscopy, Fourier Transform Infrared; X-Ray Diffraction
PubMed: 27474599
DOI: 10.1016/j.carbpol.2016.05.102 -
Nanomedicine (London, England) May 2017In this study, the effects of liposome characteristics on oral absorption of doxorubicin, as a hydrophilic low-permeability drug, were investigated.
AIM
In this study, the effects of liposome characteristics on oral absorption of doxorubicin, as a hydrophilic low-permeability drug, were investigated.
MATERIALS & METHODS
Different doxorubicin-loaded liposomes were prepared, characterized and orally administered to 18 groups of rats. Plasma concentrations of doxorubicin and its aglycone metabolite were measured, and Caco-2 uptake and transport of optimum liposomes were investigated.
RESULTS
After studying different factors, a fourfold increase in oral bioavailability was achieved with the non-PEGylated, 120-nm-sized positively charged rigid liposomes (lipid to drug ratio = 10). The extent of drug's first-pass metabolism as well as endocytosis of nanoparticles were markedly affected by liposomal formulation.
CONCLUSION
Oral absorption is highly dependent on liposomal properties, and optimum formulations are effective for low-permeability drugs.
Topics: Administration, Oral; Animals; Antibiotics, Antineoplastic; Biological Availability; Caco-2 Cells; Doxorubicin; Humans; Liposomes; Male; Rats; Rats, Sprague-Dawley
PubMed: 28447868
DOI: 10.2217/nnm-2017-0007 -
Carbohydrate Polymers Feb 2020An ultrafast (e.g. 75 s) synthesis of carboxymethyl xanthan gum (CMXG) capped gold nanoparticles (AuNPs) (CMXG@AuNPs) was developed using microwave irradiation (MWI)...
An ultrafast (e.g. 75 s) synthesis of carboxymethyl xanthan gum (CMXG) capped gold nanoparticles (AuNPs) (CMXG@AuNPs) was developed using microwave irradiation (MWI) method. The synthesis of AuNPs was optimized by varying CMXG amount, gold ion concentration, and MWI time. The CMXG@AuNPs exhibited a spherical shape, high crystallinity, and narrow size distribution (i.e. 8-10 nm). The electrostatic interaction-mediated the loading of doxorubicin (DOX) onto CMXG@AuNPs. The release of DOX, loaded on CMXG@AuNPs was extensive in an acidic condition but negligible at physiological pH value. The in vitro anticancer efficacy of DOX loaded on CMXG@AuNPs (i.e. DOX@CMXG@AuNPs) in the presence of an ionophore (i.e. nigericin) was about 4.6 folds higher than that of free DOX. Flow cytometry revealed that DOX@CMXG@AuNPs exhibited a higher cellular uptake under an acidic condition than free DOX. CMXG@AuNPs showed unique excellence in the pH-responsive DOX-releasing property and the cancer cell-killing capability.
Topics: Antineoplastic Agents; Biological Transport; Cell Line, Tumor; Chemistry Techniques, Synthetic; Doxorubicin; Drug Carriers; Drug Liberation; Gold; Humans; Metal Nanoparticles; Microwaves; Polysaccharides, Bacterial
PubMed: 31826400
DOI: 10.1016/j.carbpol.2019.115511 -
Molecules (Basel, Switzerland) Jul 2018A heterobifunctional reactive oxygen species (ROS)-responsive linker for directed drug assembly onto and delivery from a quantum dot (QD) nanoparticle carrier was...
A heterobifunctional reactive oxygen species (ROS)-responsive linker for directed drug assembly onto and delivery from a quantum dot (QD) nanoparticle carrier was synthesized and coupled to doxorubicin using -(3-dimethylaminopropyl)-'-ethylcarbodiimide hydrochloride (EDC)/sulfo⁻NHS coupling. The doxorubicin conjugate was characterized using ¹H NMR and LC-MS and subsequently reacted under conditions of ROS formation (Cu/H₂O₂) resulting in successful and rapid thioacetal oxidative cleavage, which was monitored using ¹H NMR.
Topics: Doxorubicin; Magnetic Resonance Spectroscopy; Molecular Structure; Nanoparticles; Oxidation-Reduction; Peptides; Quantum Dots; Reactive Oxygen Species
PubMed: 30037071
DOI: 10.3390/molecules23071809 -
Colloids and Surfaces. B, Biointerfaces Oct 2019In an ideal delivery system, carrier nanoparticles are used as a promising alternative with minimized adverse effects to treat a variety of diseases. The purpose of this...
In an ideal delivery system, carrier nanoparticles are used as a promising alternative with minimized adverse effects to treat a variety of diseases. The purpose of this study was to create a targeted delivery system for doxorubicin hydrochloride (DOX-HCl), using FeO-L@HSA-β-cyclodextrin (β-CD)/Allyl amine nanoparticles. In this study, magnetite nanoparticles (FeO) were produced by co-precipitation, while albumin nanoparticles (HSA) were produced by the desolvation method. The properties of the nanoparticles were studied by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), and vibrating sample magnetometer (VSM). To evaluate the loading of the drug on the synthesized nanoparticles, ultraviolet-visible spectrophotometry (UV-Vis) and atomic force microscopy (AFM) were used. DOX-HCl loading was studied by two experiments: an optimization method (OM) and a one-factor-at-a-time method (OFATM). Response surface methodology (RSM) was utilized to optimize the parameters. The optimal conditions for drug loading of nanoparticles in OM and OFATM methods were 81.46% and 77%, respectively. The release of DOX-HCl drug from the synthesized nanoparticles at a temperature of 37 °C and specific time in pH 5.3 and pH 7.4 was 83.35% and 38.39%, respectively. To examine the cytotoxicity of nanoparticles with drugs, the MTT assay was performed using MCF-7 cancer cells. Finally, cell uptake was tested using inductively coupled plasma-mass spectrometry (ICP-MS).
Topics: Antibiotics, Antineoplastic; Cell Survival; Doxorubicin; Drug Carriers; Drug Liberation; Endocytosis; Factor Analysis, Statistical; Ferrosoferric Oxide; Humans; Kinetics; Lysine; MCF-7 Cells; Magnetite Nanoparticles; Serum Albumin, Human; beta-Cyclodextrins
PubMed: 31362156
DOI: 10.1016/j.colsurfb.2019.110368 -
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