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Langmuir : the ACS Journal of Surfaces... Jan 2017Azobenzene-contained glycolipids GlyAzoCns, newly structured azobenzene derivatives, which have an azobenzene moiety between the galactosyl and carbon chains of various...
Azobenzene-contained glycolipids GlyAzoCns, newly structured azobenzene derivatives, which have an azobenzene moiety between the galactosyl and carbon chains of various sizes, have been synthesized. The GlyAzoCns undergo reversible photoinduced isomerization in both ethanol solution (free state) and liposomal bilayer (restricted state) upon irradiation with UV and vis light alternately. The drug release of Liposome@Gly induced by isomerization was found to be an instantaneous behavior. The photoinduced control of DOX release from liposome was investigated in various modes. The Liposome@Glys have been found to keep the entrapped DOX stably in the dark with less than 10% leakage in 10 h but release nearly 100% of cargos instantaneously with UV irradiation. The molecular structure of GlyAzoCns and the property of the liposomal bilayer were considered as important factors influencing drug release. Among the synthesized GlyAzoCns, GlyAzoC7 was shown to be the most efficient photosensitive actuator for controlling drug release. A lower proportion of cholesterol in Liposome@Glys was conducive to promote the release amount. Results indicated that the synthesized GlyAzoCns could act as a role of smart actuators in the liposome bilayer and control the drug to release temporarily and quantitatively.
Topics: Azo Compounds; Cholesterol; Doxorubicin; Drug Liberation; Glycolipids; Liposomes; Time Factors; Ultraviolet Rays
PubMed: 27668306
DOI: 10.1021/acs.langmuir.6b03051 -
Annals of Oncology : Official Journal... Jul 2007Palmar-plantar erythrodysesthesia (PPE), also called hand-foot syndrome or hand-to-foot syndrome, is a distinctive and relatively frequent dermatologic toxic reaction... (Review)
Review
Palmar-plantar erythrodysesthesia (PPE), also called hand-foot syndrome or hand-to-foot syndrome, is a distinctive and relatively frequent dermatologic toxic reaction associated with certain chemotherapeutic agents. Pegylated liposomal doxorubicin (PLD), a long-circulating formulation of doxorubicin in which doxorubicin hydrochloride is encapsulated within pegylated liposomes, is approved to treat patients with metastatic breast cancer, advanced ovarian cancer, and acquired immunodeficiency syndrome-related Kaposi's sarcoma. The incidence of PPE is increased in patients receiving PLD compared with conventional doxorubicin. In studies that utilized the currently approved dose of PLD (50 mg/m(2) every 4 weeks), approximately 50% of all patients receiving PLD experienced PPE, and approximately 20% experienced grade 3 PPE. The pathophysiology of PPE, as it occurs with any drug with which it is associated, is not well understood. Studies evaluating the development of PPE specifically associated with PLD have not fully elucidated the mechanism; however, data support the roles of drug excretion in sweat and local pressure as contributors. When PPE develops, clinical interventions with respect to altering PLD administration include dose reduction, less frequent dosing, and ultimately, drug withdrawal with several consequences on treatment efficacy. This article will review the available data regarding the etiology and potential management strategies of PPE associated with PLD.
Topics: Antineoplastic Agents; Doxorubicin; Female; Foot; Hand; Humans; Ovarian Neoplasms; Polyethylene Glycols; Skin Diseases
PubMed: 17229768
DOI: 10.1093/annonc/mdl477 -
Technology in Cancer Research &... Apr 2016Our study aimed to investigate the effect of ultrasonic thermotherapy on the targeted delivery of liposomal doxorubicin to superficial tumors, local drug concentrations...
Our study aimed to investigate the effect of ultrasonic thermotherapy on the targeted delivery of liposomal doxorubicin to superficial tumors, local drug concentrations in tumor tissue, and the curative effect of chemotherapy. Twenty rabbits with VX2 tumors transplanted into the superficial muscle of the hind limb were randomly assigned to the following 4 treatment groups: (1) free doxorubicin, (2) liposomal doxorubicin hydrochloride, (3) liposomal doxorubicin hydrochloride plus 41 °C thermotherapy, and (4) liposomal doxorubicin hydrochloride plus 43 °C thermotherapy. Ultrasonic thermotherapy was delivered at 41 °C to 43 °C. Plasma, tumor, and organ/tissue homogenates were analyzed by high-pressure liquid chromatography to determine doxorubicin concentrations. The drug concentration in plasma and tumor tissue was significantly higher in the liposomal doxorubicin hydrochloride plus thermotherapy group than in the liposomal doxorubicin hydrochloride and free doxorubicin groups, but there were no significant differences among the 4 groups in the concentration in heart or kidney tissue. Combining thermotherapy with liposomal doxorubicin hydrochloride chemotherapy significantly increased the concentration of the drug in tumor tissue. The doxorubicin concentration was significantly higher in the liposomal doxorubicin hydrochloride plus 41 °C thermotherapy group.
Topics: Animals; Antibiotics, Antineoplastic; Carcinoma, Squamous Cell; Cell Line, Tumor; Combined Modality Therapy; Doxorubicin; Drug Screening Assays, Antitumor; Hyperthermia, Induced; Neoplasm Transplantation; Polyethylene Glycols; Rabbits; Tissue Distribution; Treatment Outcome; Tumor Burden
PubMed: 25882881
DOI: 10.1177/1533034615580441 -
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 -
PloS One 2019Doxorubicin (DOX) is a widely used chemotherapeutic anticancer drug. Its intrinsic fluorescence properties enable investigation of tumor response, drug distribution and...
Doxorubicin (DOX) is a widely used chemotherapeutic anticancer drug. Its intrinsic fluorescence properties enable investigation of tumor response, drug distribution and metabolism. First phantom studies in vitro showed optoacoustic property of DOX. We therefore aimed to further investigate the optoacoustic properties of DOX in biological tissue in order to explore its potential as theranostic agent. We analysed doxorubicin hydrochloride (Dox·HCl) and liposomal encapsulated doxorubicin hydrochloride (Dox·Lipo), two common drugs for anti-cancer treatment in clinical medicine. Optoacoustic measurements revealed a strong signal of both doxorubicin substrates at 488 nm excitation wavelength. Post mortem analysis of intra-tumoral injections of DOX revealed a detectable optoacoustic signal even at three days after the injection. We thereby demonstrate the general feasibility of doxorubicin detection in biological tissue by means of optoacoustic tomography, which could be applied for high resolution imaging at mesoscopic depths dictated by effective penetration of visible light into the biological tissues.
Topics: Animals; Cell Line, Tumor; Disease Models, Animal; Doxorubicin; Feasibility Studies; Female; Humans; Injections, Intralesional; Mice; Neoplasms; Photoacoustic Techniques; Pilot Projects; Polyethylene Glycols; Theranostic Nanomedicine; Tomography
PubMed: 31150471
DOI: 10.1371/journal.pone.0217576 -
Leukemia & Lymphoma Jun 2018
Randomized Controlled Trial
Topics: Analysis of Variance; Antibiotics, Antineoplastic; Doxorubicin; Humans; Multiple Myeloma; Polyethylene Glycols; Therapeutic Equivalency; Treatment Outcome
PubMed: 28994344
DOI: 10.1080/10428194.2017.1382692 -
Journal of Nanoscience and... Oct 2018The doxorubicin hydrochloride (DOX)-loaded poly(L-lactic acid)/hydroxyapatite/gelatin (PLLA/a-HA/gelatin) particle was prepared by emulsion/solvent evaporation method...
The doxorubicin hydrochloride (DOX)-loaded poly(L-lactic acid)/hydroxyapatite/gelatin (PLLA/a-HA/gelatin) particle was prepared by emulsion/solvent evaporation method using CH2Cl2 as a solvent. HA nanoparticles were prepared via a facile chemical precipitate method and HA nanoparticles were functionalized by adding aminopropyltriethoxysilane (APTS) under microwave radiation. The physical and chemical properties of HA and modified HA were characterized by XRD, TEM, FT-IR, and XPS. Furthermore, the release of DOX from PLLA/a-HA/gelatin was also estimated. Results indicated that HA was successfully functionalized via APTS and functionalized HA has primary amino groups on its surface which improved the surface chemical compatibility between HA and PLLA matrix. The prepared PLLA/a-HA/gelatin was considered as a drug release carrier to study sustained release behavior of doxorubicin hydrochloride (DOX). The PLLA/a-HA/gelatin can effectively prolong the release time of DOX and exhibits a stable and sustainable drug release which indicates that the PLLA/a-HA/gelatin nanocomposite material could serve as a potential carrier for novel drug release system.
Topics: Antibiotics, Antineoplastic; Delayed-Action Preparations; Doxorubicin; Drug Liberation; Durapatite; Gelatin; Polyesters; Propylamines; Silanes
PubMed: 29954564
DOI: 10.1166/jnn.2018.15507 -
International Journal of Pharmaceutics Feb 2012The present study discusses design of doxorubicin hydrochloride (Dox) loaded lipid based nanocarrier (LIPOMER) for oral delivery. High entrapment (>90 %) and high...
The present study discusses design of doxorubicin hydrochloride (Dox) loaded lipid based nanocarrier (LIPOMER) for oral delivery. High entrapment (>90 %) and high loading (38.11 ± 0.37 %w/w) of hydrophilic Dox in lipid nanocarrier of polyglyceryl-6-distearate was achieved using poly(methyl vinyl ether-co-maleic anhydride) (Gantrez AN 119) and a modified nanoprecipitation method. Dox-LIPOMER revealed nanosize (314 ± 16.80 nm) and negative zeta potential (-25.00 ± 2.41 mV). Dox-LIPOMER exhibits sustained release in vitro and was influenced by ionic strength of dissolution medium. DSC and XRD studies suggested amorphous nature of Dox in LIPOMER. TEM revealed spherical morphology of Dox-LIPOMER. Dox-LIPOMER was stable up to 12 months at 25 °C/60 % RH. A 384 % enhancement in oral bioavailability compared to Dox solution was observed following Dox-LIPOMER administration at 10 mg/kg body weight. Superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) assay data of heart and kidney tissues of rats treated with Dox-LIPOMER were comparable with untreated rats. Dox-LIPOMER represents a potential safe drug delivery system for oral administration.
Topics: Administration, Oral; Animals; Antibiotics, Antineoplastic; Biological Availability; Calorimetry, Differential Scanning; Catalase; Chemical Precipitation; Chemistry, Pharmaceutical; Crystallography, X-Ray; Doxorubicin; Drug Carriers; Drug Compounding; Drug Stability; Female; Glycerol; Heart; Hydrophobic and Hydrophilic Interactions; Kidney; Lipids; Maleates; Malondialdehyde; Microscopy, Electron, Transmission; Myocardium; Nanoparticles; Nanotechnology; Osmolar Concentration; Oxidative Stress; Polymers; Polyvinyls; Powder Diffraction; Rats; Rats, Sprague-Dawley; Solubility; Superoxide Dismutase; Technology, Pharmaceutical
PubMed: 22155412
DOI: 10.1016/j.ijpharm.2011.11.035 -
International Journal of Biological... Aug 2017Controlled release of drugs has been widely researched in biomedical area. Nanoparticles (NPs) as ideal drug carriers are often used to facilitate improvements in the...
Controlled release of drugs has been widely researched in biomedical area. Nanoparticles (NPs) as ideal drug carriers are often used to facilitate improvements in the therapeutic index of drugs. In this study, natural polymers carboxymethyl chitosan (CMC) and lysozyme (LY) were mixed to prepare CMC-LY NPs by electrostatic self-assembly interactions. In addition, layered silicate rectorite (REC) was introduced into NPs to explore the effect on the encapsulation efficacy and controlled release of doxorubicin hydrochloride (DOX). It was confirmed that the average size of NPs increased with the addition of REC, and the interlayer distance of REC in NPs was enlarged because of the intercalation with polymer chains. Besides, the encapsulation efficiency and loading capacity of DOX in NPs increased markedly with the accretion of REC. The incorporation of REC into NPs could reduce the initial burst release and prolong the therapeutic time. Such results suggest that the REC-intercalated NPs are promising anticancer drug carriers for efficient cancer therapy.
Topics: Aluminum Silicates; Chitosan; Delayed-Action Preparations; Doxorubicin; Drug Carriers; Drug Liberation; Minerals; Models, Molecular; Molecular Conformation; Muramidase; Nanoparticles
PubMed: 28315438
DOI: 10.1016/j.ijbiomac.2017.03.059 -
Journal of Oncology Pharmacy Practice :... Jun 2019The EPOCH regimen, consisting of vincristine sulfate, doxorubicin hydrochloride, and etoposide phosphate, is typically administered by continuous infusion over four days...
Stability of vincristine sulfate, doxorubicin hydrochloride and etoposide phosphate admixtures in polyisoprene elastomeric pump supporting transition of the EPOCH regimen to outpatient care.
BACKGROUND
The EPOCH regimen, consisting of vincristine sulfate, doxorubicin hydrochloride, and etoposide phosphate, is typically administered by continuous infusion over four days to oncology inpatients. If the EPOCH regimen was available to be administered through portable elastomeric pumps, chemotherapy could be transitioned to an outpatient setting, reducing inpatient bed days and overall healthcare costs. However, a lack of stability data for the admixtures in the elastomeric infusion devices currently prevents the transition of the regime to an outpatient setting. The purpose of this study is to determine the physical and chemical stability of the admixture in polyisoprene elastomeric pumps under different storage conditions to support the transition of the EPOCH regime to an outpatient setting.
METHODS
The physico-chemical stability of three admixtures at a range of clinically relevant concentrations compounded in polyisoprene elastomeric infusors was determined when refrigerated at 2-6℃ over a 14-day period followed by 35℃ up to 7 days in the dark, and under standardized fluorescent light to simulate scenarios in clinical practice.
RESULTS
All tested admixtures were compatible and the drugs were stable in the elastomeric infusors for up to 14 days when stored at 2-6℃ followed by 7 days at 35℃ in the dark, with nominal losses of <5%. The major degradant of etoposide phosphate was its active form etoposide. There was no degradation (<1% loss) found when the admixture was exposed to a standardized fluorescent light dose of 80 klux-h (25℃) for 10 h. The temperature and light conditions the infusors were exposed to during the stability study were more severe than the conditions determine during clinical administration.
CONCLUSION
The extended stability of the three infusional admixtures compounded in elastomeric infusion pumps demonstrated herein permits advance preparation and storage of these drugs, reducing pharmacy compounding resources. The demonstrated stability at 35℃ and under light exposure, conditions more severe than those experienced during clinical practice, support continuous infusions for up to seven days from the elastomeric infusors without a loss of potency. The proven stability of the EPOCH regimens in the tested elastomeric infusion device supports the transition of treatment to an outpatient setting which will reduce inpatient bed days and overall healthcare costs.
Topics: Ambulatory Care; Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Drug Stability; Elastomers; Etoposide; Humans; Infusion Pumps; Organophosphorus Compounds; Vincristine
PubMed: 29540104
DOI: 10.1177/1078155218764285