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International Journal of Pharmaceutics Mar 2023Osteosarcoma (OS) is the most common malignant tumor of the bone that affects children and adolescents, and its treatment usually involves doxorubicin hydrochloride...
Osteosarcoma (OS) is the most common malignant tumor of the bone that affects children and adolescents, and its treatment usually involves doxorubicin hydrochloride (DOX). However, the drug resistance and side effects caused by high-dose DOX infusion greatly hinder its therapeutic effects. To achieve efficient OS treatment with low toxicity, an injectable rhein (RH)-assisted crosslinked hydrogel (PVA@RH@DOX hydrogel, PRDH) was designed, which was prepared by loading DOX and RH into a polyvinyl alcohol (PVA) solution. The cytotoxicity assay and live/dead staining results showed that the combination of RH and DOX more effectively killed OS cells, producing excellent effects at low concentrations of DOX. The wound healing and transwell test results proved that PRDH could significantly inhibit the metastasis and invasion of OS cells. PRDH showed a long-lasting antitumor effect after injection of a single dose, significantly suppressing the proliferation and metastasis of OS and achieving the strategy of a single administration for long-term treatment. Excitingly, RH facilitated hydrogel formation by assisting with PVA crosslinking. This system provides an alternative regimen and broadens the horizon for the clinical treatment of OS.
Topics: Child; Humans; Adolescent; Hydrogels; Osteosarcoma; Doxorubicin; Bone Neoplasms; Cell Line, Tumor
PubMed: 36702387
DOI: 10.1016/j.ijpharm.2023.122637 -
International Journal of Biological... Jul 2023Hybrid nanoparticles made up of zein and various stabilizers were developed and characterized. In detail, a zein concentration of 2 mg/ml was blended with various...
Hybrid nanoparticles made up of zein and various stabilizers were developed and characterized. In detail, a zein concentration of 2 mg/ml was blended with various amounts of different phospholipids or PEG-derivatives in order to obtain formulations with suitable physico-chemical properties for drug delivery purposes. Doxorubicin hydrochloride (DOX) was used as a model of a hydrophilic compound and its entrapment efficiency, release profile and cytotoxic activity were investigated. Photon correlation spectroscopy showed that the best formulations were obtained using DMPG, DOTAP and DSPE-mPEG2000 as stabilizers of zein nanoparticles, which were characterized by an average diameter of ~100 nm, a narrow size distribution and a significant time- and temperature-dependent stability. The interaction between protein and stabilizers was confirmed through FT-IR analysis, while TEM analysis showed the presence of a shell-like structure around the zein core. The release profiles of the drug from the zein/DSPE-mPEG2000 nanosystems, evaluated at two pHs (5.5 and 7.4), showed a prolonged and constant leakage of the drug. The encapsulation of DOX within zein/DSPE-mPEG2000 nanosystems did not compromise its biological efficacy, demonstrating the potential application of these hybrid nanoparticles as drug carriers.
Topics: Doxorubicin; Zein; Spectroscopy, Fourier Transform Infrared; Drug Delivery Systems; Drug Carriers; Nanoparticles; Particle Size
PubMed: 37285879
DOI: 10.1016/j.ijbiomac.2023.125222 -
ACS Nano Jan 2018A sperm-driven micromotor is presented as a targeted drug delivery system, which is appealing to potentially treat diseases in the female reproductive tract. This system...
A sperm-driven micromotor is presented as a targeted drug delivery system, which is appealing to potentially treat diseases in the female reproductive tract. This system is demonstrated to be an efficient drug delivery vehicle by first loading a motile sperm cell with an anticancer drug (doxorubicin hydrochloride), guiding it magnetically, to an in vitro cultured tumor spheroid, and finally freeing the sperm cell to deliver the drug locally. The sperm release mechanism is designed to liberate the sperm when the biohybrid micromotor hits the tumor walls, allowing it to swim into the tumor and deliver the drug through the sperm-cancer cell membrane fusion. In our experiments, the sperm cells exhibited a high drug encapsulation capability and drug carrying stability, conveniently minimizing toxic side effects and unwanted drug accumulation in healthy tissues. Overall, sperm cells are excellent candidates to operate in physiological environments, as they neither express pathogenic proteins nor proliferate to form undesirable colonies, unlike other cells or microorganisms. This sperm-hybrid micromotor is a biocompatible platform with potential application in gynecological healthcare, treating or detecting cancer or other diseases in the female reproductive system.
Topics: Antineoplastic Agents; Doxorubicin; Drug Carriers; Drug Delivery Systems; Drug Liberation; Female; Genital Neoplasms, Female; HeLa Cells; Humans; Male; Spermatozoa
PubMed: 29202221
DOI: 10.1021/acsnano.7b06398 -
ACS Biomaterials Science & Engineering Oct 2021Iron-based metal-organic frameworks (MOFs) have been reported to have great potential for encapsulating doxorubicin hydrochloride (DOX), which is a frequently used...
Iron-based metal-organic frameworks (MOFs) have been reported to have great potential for encapsulating doxorubicin hydrochloride (DOX), which is a frequently used anthracycline anticancer drug. However, developing a facile approach to realize high loading capacity and efficiency as well as controlled release of DOX in MOFs remains a huge challenge. Herein, we synthesized water-stable MIL-101(Fe)-CH through a microwave-assisted method. It was found the nano-MOFs acted as nanosponges when soaked in a DOX alkaline aqueous solution with a loading capacity experimentally up to 24.5 wt %, while maintaininga loading efficiency as high as 98%. The mechanism of the interaction between DOX and nanoMOFs was investigated by absorption spectra and density functional theory (DFT) calculations, which revealed that the deprotonated DOX was electrostatically adsorbed to the unsaturated FeOCl(COO)·HO (named Fe trimers). In addition, the as-designed poly(ethylene glycol--propylene glycol) (F127) modified nanoparticles (F127-DOX-MIL) could be decomposed under the stimulation of glutathione (GSH) and ATP. As a result, DOX and Fe(III) ions were released, and they could undergo a Fenton-like reaction with the endogenous HO to generate the highly toxic hydroxyl radical (·OH). The in vitro experiments indicated that F127-DOX-MIL could cause remarkable Hela cells inhibition through chemotherapy and chemodynamic therapy. Our study provides a new strategy to design a GSH/ATP-responsive drug-delivery nanosystem for chemo/chemodynamic therapy.
Topics: Doxorubicin; Ferric Compounds; HeLa Cells; Humans; Hydrogen Peroxide; Metal-Organic Frameworks
PubMed: 34550683
DOI: 10.1021/acsbiomaterials.1c00874 -
Analytica Chimica Acta Jan 2024Liposomal formulations have traditionally been considered the most therapeutically effective drug delivery systems (DDS). However, their pharmacokinetics study and...
Liposomal formulations have traditionally been considered the most therapeutically effective drug delivery systems (DDS). However, their pharmacokinetics study and efficacy assessment are still challenging given size heterogeneity and unknown forms in vivo. The pharmacodynamic evaluation that solely analyzes total drug concentration is unfit for the liposomal formulation study. Hence, it is crucial to develop effective strategies for the separation and analysis of different forms of liposomal formulations in order to contribute to the study of pharmacokinetic profiles associated with both liposome-incorporated and non-liposomal drugs. (84) RESULTS: A laboratory-built circular nonuniform electric field gel electrophoresis (CNEFGE) system was developed in this study for simultaneous separation and analysis of various forms of doxorubicin hydrochloride (DOX•HCl) liposomes. Liposomes were effectively fractionized based on their size and higher concentration in situ in the concentration zone, obtaining liposome recovery >95 % and a 3.04 concentration factor. It was found that the technique could be used to evaluate not only the size distribution of liposomes but also the drug loading capacity related to size. The charge-to-size-based separation mechanism has also allowed the simultaneous separation of liposome-entrapped drugs, protein-bound drugs, and free drugs in various forms, and the technique has been successfully employed in serum. Moreover, the quantification analysis of liposomes incubated with serum for 72 h showed that the proportion of the ratio of DOX•HCl in liposome-entrapped drugs, protein-bound drugs, and free drugs is approximately 97:2:1. (143) SIGNIFICANCE: Using the separation principle of gel electrophoresis and the electrification characteristics of drug carriers, this study developed and implemented an efficient approach for the simultaneous separation and concentration of multiple forms of drug liposomes in vivo. This approach offers a wide range of applications in the pharmacokinetics, efficacy, and safety evaluation of drug carriers and liposomes. (56).
Topics: Liposomes; Drug Carriers; Drug Delivery Systems; Doxorubicin; Electrophoresis
PubMed: 38182347
DOI: 10.1016/j.aca.2023.342110 -
Environmental Toxicology Jun 2021Colorectal cancer (CC) is an important human malignancy with high cancer related death worldwide. The chemotherapy using doxorubicin hydrochloride is one of the most...
Colorectal cancer (CC) is an important human malignancy with high cancer related death worldwide. The chemotherapy using doxorubicin hydrochloride is one of the most common cancer therapeutic methods. However, drug resistance lowers the treatment efficacy in CC patients. The combination therapies seem to be more promising by taking the advantage of synergistic effects. The present study aimed to evaluate a new strategy to enhance the anticancer activity of doxorubicin in Caco-2 CC cell line by co-administration of melatonin. The effects of doxorubicin, melatonin, and their combinations (Dox-Mel) were investigated on the proliferation and viability, morphological alterations, and tumor spheroid formation. Flow cytometry was employed to compare the apoptotic situation of the cells in study groups. Changes in metastatic potential of the cells were assessed by wound healing assay and trans-well migration assays. Moreover, expression of BAX, SMAC, BCL-2, SURVIVIN, MMP-2, and MMP-9 genes were evaluated by quantitative real time PCR and western blotting. Our study showed that doxorubicin, melatonin, and Dox-Mel significantly decreased the proliferation and viability, tumor spheroid formation, invasion, and migration. Furthermore, the changes were in a concentration and time dependent manner. There was an increase in apoptosis rate in the treatment groups. Expression of genes involved in apoptosis and cell motility were altered significantly. It was observed that anticancer activity of Dox-Mel combination was significantly more than doxorubicin and melatonin treatments alone. We showed an enhanced apoptotic and anticancer activity of doxorubicin and melatonin combination chemotherapy on CC cell line than doxorubicin or melatonin treatments alone. This combination could promote the treatment efficiency and alleviate the un-intended side effects by lowering the dose of doxorubicin prescription.
Topics: Apoptosis; Caco-2 Cells; Cell Line, Tumor; Cell Proliferation; Colorectal Neoplasms; Doxorubicin; Humans; Melatonin
PubMed: 33507000
DOI: 10.1002/tox.23105 -
Drug Delivery and Translational Research Dec 2022Limited targeted therapies are available for triple-negative breast cancer (TNBC). Thus, the current research focused on developing a targeted protein nanoparticle for...
Limited targeted therapies are available for triple-negative breast cancer (TNBC). Thus, the current research focused on developing a targeted protein nanoparticle for TNBC. First, the doxorubicin hydrochloride (Dox)-loaded genipin-crosslinked whey protein nanoparticles (WD) were prepared and optimised by the QbD method using BBD. The hydrodynamic diameter of WD was found to be 364.38 ± 49.23 nm, zeta potential -27.59 ± 1.038 mV, entrapment 63.03 ± 3.625% and Dox loading was found to be 1.419 ± 0.422%. The drug recovery after 18 months of storage was 69%. Then, it was incubated with NAC to obtain modified WD (CyWD). WD followed first-order release kinetics, whereas CyWD followed the Higuchi model. Hemagglutination and hemolysis were not found qualitatively in WD and CyWD. Upon injecting the nanoformulations to 4T1-induced mice, the highest efficacy was found to be in CyWD followed by WD and Dox injection. Upon histopathological observance, it was found that the CyWD group gave the most significant damage to the 4T1 tumour tissue. Thus, NAC-modified protein nanoparticles carrying chemotherapeutic agents can be an excellent targeted therapeutic system against TNBC.
Topics: Humans; Mice; Animals; Doxorubicin; Triple Negative Breast Neoplasms; Whey Proteins; Acetylcysteine; Cell Line, Tumor; Nanoparticles
PubMed: 35499714
DOI: 10.1007/s13346-022-01169-8 -
Journal of Nanobiotechnology Sep 2022Poor in vivo targeting of tumors by chemotherapeutic drugs reduces their anti-cancer efficacy in the clinic. The discovery of over-expressed components on the tumor cell...
BACKGROUND
Poor in vivo targeting of tumors by chemotherapeutic drugs reduces their anti-cancer efficacy in the clinic. The discovery of over-expressed components on the tumor cell surface and their specific ligands provide a basis for targeting tumor cells. However, the differences in the expression levels of these receptors on the tumor cell surface limit the clinical application of anti-tumor preparations modified by a single ligand. Meanwhile, toxicity of chemotherapeutic drugs leads to poor tolerance to anti-tumor therapy. The discovery of natural active products antagonizing these toxic side effects offers an avenue for relieving cancer patients' pain during the treatment process. Since the advent of nanotechnology, interventions, such as loading appropriate drug combinations into nano-sized carriers and multiple tumor-targeting functional modifications on the carrier surface to enhance the anti-tumor effect and reduce toxic and side effects, have been widely used for treating tumors.
RESULTS
Nanocarriers containing doxorubicin hydrochloride (DOX) and salvianolic acid A (Sal A) are spherical with a diameter of about 18 nm; the encapsulation efficiency of both DOX and salvianolic acid A is greater than 80%. E-[c(RGDfK)]/folic acid (FA) co-modification enabled nanostructured lipid carriers (NLC) to efficiently target a variety of tumor cells, including 4T1, MDA-MB-231, MCF-7, and A549 cells in vitro. Compared with other preparations (Sal A solution, NLC-Sal A, DOX solution, DOX injection, Sal A/DOX solution, NLC-DOX, NLC-Sal A/DOX, and E-[c(RGDfK)]/FA-NLC-Sal A/DOX) in this experiment, the prepared E-[c(RGDfK)]/FA-NLC-Sal A/DOX had the best anti-tumor effect. Compared with the normal saline group, it had the highest tumor volume inhibition rate (90.72%), the highest tumor weight inhibition rate (83.94%), led to the highest proportion of apoptosis among the tumor cells (61.30%) and the lowest fluorescence intensity of proliferation among the tumor cells (0.0083 ± 0.0011). Moreover, E-[c(RGDfK)]/FA-NLC-Sal A/DOX had a low level of nephrotoxicity, with a low creatinine (Cre) concentration of 52.58 μmoL/L in the blood of mice, and no abnormalities were seen on pathological examination of the isolated kidneys at the end of the study. Sal A can antagonize the nephrotoxic effect of DOX. Free Sal A reduced the Cre concentration of the free DOX group by 61.64%. In NLC groups, Sal A reduced the Cre concentration of the DOX group by 42.47%. The E-[c(RGDfK)]/FA modification reduced the side effects of the drug on the kidney, and the Cre concentration was reduced by 46.35% compared with the NLC-Sal A/DOX group. These interventions can potentially improve the tolerance of cancer patients to chemotherapy.
CONCLUSION
The E-[c(RGDfK)]/FA co-modified DOX/Sal A multifunctional nano-drug delivery system has a good therapeutic effect on tumors and low nephrotoxicity and is a promising anti-cancer strategy.
Topics: Animals; Antibiotics, Antineoplastic; Caffeic Acids; Cell Line, Tumor; Creatinine; Doxorubicin; Drug Carriers; Drug Combinations; Folic Acid; Lactates; Ligands; Lipids; Mice; Mice, Inbred BALB C; Saline Solution
PubMed: 36153589
DOI: 10.1186/s12951-022-01628-x -
AAPS PharmSciTech Jul 2020The adverse side effects and toxicity caused by the non-targeted delivery of doxorubicin has emphasized the demand of emerging a targeted delivery system. The goal of...
The adverse side effects and toxicity caused by the non-targeted delivery of doxorubicin has emphasized the demand of emerging a targeted delivery system. The goal of this study is to enhance the delivery of doxorubicin by formulating an aptamer-labeled liposomal nanoparticle delivery system that will carry and deliver doxorubicin specifically into Her-2+ breast cancer cells. Twelve liposomal batches were prepared using different saturated (HSPC and DPPC) and unsaturated (POPC and DOPC) lipids by thin film hydration. The liposomes were characterized for their particle size, zeta potential, and drug encapsulation efficiency. The particles were also assessed for in vitro toxicity and DOX delivery into the breast cancer cells. The formulations, F1 through F12, had a small particle size of less than 200 nm and a high entrapment efficiency of about 88 ± 5%. The best formulation, F5, had a particle size of 101 ± 14nm, zeta potential of + 5.63 ± 0.46 mV, and entrapment efficiency of ≈ 93%. The cytotoxicity studies show that the DOX-loaded liposomal formulations are more effective in killing cancer cells than the free DOX in both MCF-7 and SKBR-3 cells. The uptake studies show a significant increase in the uptake of the aptamer-labeled liposomes (i.e., F5) by more than 60% into Her-2+ MCF-7 and SKBR-3 breast cancer cells compare to non-aptamer-labeled nanoparticles. F5 also shows ≈ 1.79-fold increase in uptake of DOX in the Her-2+ cells compared to the Her-2- cells. This preliminary study indicates that aptamer-labeled F5 nanoparticles among several batches showed the highest uptake as well as the targeted delivery of doxorubicin into Her-2+ breast cancer cells. Thus, aptamer targeted approach results in substantial reduction in the dose of DOX and improves the therapeutic benefits by promoting the target specificity.
Topics: Animals; Antibiotics, Antineoplastic; Breast Neoplasms; Cell Line, Tumor; Doxorubicin; Drug Delivery Systems; Female; Humans; Liposomes; Nanoparticles; Polyethylene Glycols; Receptor, ErbB-2
PubMed: 32696338
DOI: 10.1208/s12249-020-01743-8 -
Materials Science & Engineering. C,... Jan 2021Nanogel based on polysaccharides has attracted the tremendous interest due to its unique performance as drug carrier for in vivo release. In this work, the...
Nanogel based on polysaccharides has attracted the tremendous interest due to its unique performance as drug carrier for in vivo release. In this work, the multi-responsive nanogels were developed based on the tailor-modified sugarcane bagasse cellulose (SBC). In the presence of crosslinking agent cystamine bisacrylamide (CBA), the in-situ free radical copolymerization of methacrylated monocarboxylic sugarcane bagasse cellulose (MAMC-SBC) and N-isopropylacrylamide (NIPAM) in aqueous phase was conducted, thus leading to redox, pH and thermal-responsive nanogels. The results obtained from FT-IR, SEM and particle sizer showed that the nanogels were highly stable with the desired particle size ranging from 90 to 180 nm and contained targeted polymeric segments and linkage for multi-responsivity. Doxorubicin hydrochloride (DOX) as a model drug was effectively loaded into the nanogels, partly driven by strong electrostatic association; and the loading efficiency reached up to 82.7%. Moreover, the drug release could be readily manipulated by the addition of reducing agent, pH and temperature, which is attributed to the multi-responsive behavior of nanogels as carrier and synergetic effects. The performance of nanogels was also governed by the ratio of reactive MAMC-SBC and NIPAM during polymerization; and the ratio at 1:1(wt) led to the optimal structure of nanogels.
Topics: Cellulose; Doxorubicin; Drug Carriers; Hydrogen-Ion Concentration; Nanogels; Saccharum; Spectroscopy, Fourier Transform Infrared
PubMed: 33254977
DOI: 10.1016/j.msec.2020.111357