Adriamycin extravasation into subcutaneous tissues during intravenous administration results in an intense inflammatory response, which may progress to full thickness skin loss. With increased use of the potent anticancer drug adriamycin, there are increasing numbers of severe local tissue damage at the venous administration sites. We report a case of skin necrosis that was caused by extravasation of adriamycin in the treatment of multiple myeloma. When anticancer drug extravasation occurs, early recognition and adequate management is required.
Administration, Intravenous ; Doxorubicin* ; Multiple Myeloma ; Necrosis* ; Skin* ; Subcutaneous Tissue

BACKGROUNDLiver targeting drug delivery systems can improve the curative effects and relieve the cytotoxicity of the chemotherapy drugs in the treatment of liver diseases. Nanoparticles carrying therapeutic drugs are currently under hot investigation with great clinical significance. This study was aimed to investigate the different tissue distribution of the adriamycin polybutylcyanoacrylate nanoparticle (ADM-PBCA-NP) in the mice body after an injection via lateral tail vein, and to study the liver targeting effects of ADM-PBCA-NP in different diameters on normal mice liver.

METHODSOne hundred and eighty Kunming mice were randomly divided into 6 groups with 30 mice in each group (5 treatment groups of ADM-PBCA-NP in the different diameter ranges, non-conjugated free adriamycin injection was employed as the control group). A single dose of either conjugated or free adriamycin equaled 2 mg/kg of body weight was delivered via the tail vein. Five mice in each trail were sacrificed at 5, 15, 30 minutes, 1, 5 and 12 hours postinjection, respectively. The adriamycin concentrations in the respectively collected liver, kidney, spleen, heart, lung and plasma were demonstrated using a high performance liquid chromatography with fluorescence detector.

RESULTSCompared with the control group, adriamycin was hardly detected in the heart muscle of the treatment groups (P < 0.05). The nanoparticle-conjugated adriamycin was cleaned up quickly from the kidney tissue. The adriamycin concentrations of the mice liver and spleen in the experimental groups were significantly higher than that in the control group, except for the group with the nanoparticles diameters of (22.3 +/- 6.2) nm (P < 0.05). The ADM-PBCA-NP in (101.0 +/- 20.3) nm diameter had the highest liver distribution, and the second highest adriamycin distribution in liver was the group of (143.0 +/- 23.5) nm diameter (P < 0.05). Moreover, adriamycin was released slowly in the liver during the detection period in the experimental groups. ADM-PBCA-NP in (22.3 +/- 6.2) nm diameter was not distributed in the tissue of the liver, kidney, heart, spleen, and lung.

CONCLUSIONSADM-PBCA-NP in 100 - 150 nm diameter range has the best liver targeting with a characteristic of slow medicine release. It also decreases the medicine distribution in the heart, kidney and lung. In the treatment of liver cancer, the polybutylcyanoacrylate nanoparticles system has a good liver targeting ability, which increases the anticancer activity and markedly decreases the toxicity of adriamycin.

Animals ; Antineoplastic Agents ; administration & dosage ; Doxorubicin ; administration & dosage ; Drug Delivery Systems ; Enbucrilate ; administration & dosage ; Liver ; metabolism ; Mice ; Nanostructures ; Tissue Distribution

Advanced Hodgkin's disease is usually treated with six or more cycles of combination chemotherapy. Spontaneous regression of the cancer is very rarely reported in patients with Hodgkin's disease. We present an unusual case of a patient with Hodgkin's disease who experienced complete remission with a single cycle of chemotherapy, followed by pneumonia. The case was a 36-year-old man diagnosed with stage IVB mixed cellularity Hodgkin's disease in November 2000. After treatment with one cycle of COPP-ABV (cyclophosphamide, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, and vinblastine) chemotherapy without bleomycin, the patient developed interstitial pneumonia and was cared in the intensive care unit (ICU) for two months. Follow-up chest computerized tomography (CT), performed during the course of ICU care, revealed markedly improved mediastinal lymphomatous lesions. Furthermore, follow-up whole body CT and 18-fluorodeoxyglucose positron emission tomography showed complete disappearance of the lymphomatous lesions. Four years later, the patient is well and without relapse. This report is followed by a short review of the literature on spontaneous regression of Hodgkin's disease. To the best of our knowledge, this is the first case report of spontaneous remission of Hodgkin's disease in Korea.
Adult ; Antineoplastic Combined Chemotherapy Protocols/*administration & dosage ; Bleomycin/*administration & dosage ; Cyclophosphamide/*administration & dosage ; Doxorubicin/*administration & dosage ; Hodgkin Disease/*complications/*drug therapy ; Humans ; Male ; Pneumonia/*complications ; Prednisone/*administration & dosage ; Procarbazine/*administration & dosage ; Remission, Spontaneous ; Vinblastine/*administration & dosage ; Vincristine/*administration & dosage

OBJECTIVETo explore the efficacy and safety of subcutaneous injection of bortezomib in the treatment of de novo multiple myeloma (MM) patients.

METHODSA total of 36 MM patients treated with bortezomib, adriamycin and dexamethasone (PAD) from January 2012 to April 2013 were analyzed. Among them, 18 received improved PAD (improved PAD group) with the subcutaneous injection of bortezomib, another 18 received conventional PAD (PAD group). The efficacy and safety of two groups were analyzed.

RESULTSExcept 4 cases can not be assessed, 32 patients were evaluated. Of 32 cases, 19(59.4%) achieved complete remission (CR) or very good partial remission (VGPR) after induction therapy, which were 61.1% and 57.1% for PAD group and improved PAD group, respectively (P=1.000). No significant difference between the time to achieve maximum effectiveness in two groups was detected. In the PAD group, one patient (5.6%) died of serious lung infection and eight (44.4%) experienced grade 3 or higher adverse events, while only one (5.6%) discontinued treatment in improved PAD group due to similar toxicity. Compared to PAD group, grade 3 or worse adverse events was significantly reduced in improved PAD group, the most common symptoms were leucopenia (33.3% vs 61.1%, P=0.086), thrombocytopenia (50.0% vs 61.1%), anaemia (27.8% vs 16.7%), infection (16.7% vs 50.0%, P=0.075), diarrhea (5.6% vs 33.3%, P=0.088), peripheral neuropathy(0 vs 27.8%, P=0.045).

CONCLUSIONThe improved PAD regimen by changing bortezomib from intravenous administration to subcutaneous injection significantly reduced adverse events, improved the safety of clinical application of bortezomib without affecting curative effect, and had great progress.

Boronic Acids ; administration & dosage ; Bortezomib ; Dexamethasone ; administration & dosage ; Doxorubicin ; administration & dosage ; Humans ; Injections, Subcutaneous ; Multiple Myeloma ; drug therapy ; Pyrazines ; administration & dosage ; Remission Induction

OBJECTIVETo approach the sequential release of antitumor drugs and promote the effect of chemotherapy.

METHODSAdriamycin (ADM) and carboplatin (CBP) were respectively microcapsulated with ethylcellulose by organic phase separation. The morphology and sizes of the microcapsules were observed and measured with light microscope and scanning electromicroscope. The contents and the release rates of ADM and CBP in microcapsules were measured with fluorescence spectrophotometer and high-efficiency phantom chromatic (HPC) spectrum respectively. The antitumor sensitivity test in vitro was devised with MTT assay.

RESULTSThe microcapsules of ADM and CBP were spherical in shape with diameters of 196 +/- 64 micro m and 214 +/- 48 micro m respectively. The contents of one-layer and two-layer CBP and ADM microcapsules were 51.4%, 35.7% and 39.8% respectively, with the release rates in vitro of 62.4%/day, 54.8%/day and 48.2%/8 h. The results of drug sensitivity test in vitro demonstrated that the current preparation has never affected the stability and antitumor activity of CBP and ADM.

CONCLUSIONMicrocapsules with different drugs and different thickness of material have different release rate. Combined arterial chemoembolization with different microcapsules could approach the sequential release and promote the effect of chemotherapy.

Antineoplastic Agents ; administration & dosage ; chemistry ; Carboplatin ; administration & dosage ; Cellulose ; administration & dosage ; analogs & derivatives ; Chemoembolization, Therapeutic ; Doxorubicin ; administration & dosage ; Drug Delivery Systems ; Humans ; Tumor Cells, Cultured

Magnetic chitosan (CS) nano-spheres were prepared by the modified suspension cross-linking technique. The results demonstrated that the magnetic drug nano-spheres are mainly spherical in form with a size of 200 to 800 nm, and show good magnetic responsivity. Here, Doxorubicin was used as exam drug. Glutaraldehyde connects Doxorubicin to CS by the chemical bond (-N = C-), and the drug content is in range of 1% to 15% (w/w). The chemical bond is broken depending on pH, so pH is the important factor for the release of doxorubicin. The doxorubicin release was 22.0%, 13.4%, and 4.1% in the space of 7d, when pH was 1, 2, 4. So the nano-spheres are pH-sensitive magnetic targeting drug micro-spheres.
Chitosan ; chemistry ; Doxorubicin ; administration & dosage ; Drug Carriers ; chemical synthesis ; Drug Delivery Systems ; methods ; Magnetics ; Nanospheres ; chemistry

OBJECTIVE: To determine the short and mid-term effect of paravertebral adriamycin injection under CT guidance on intractable postherpetic neuralgia (PHN). METHODS: From January 2010 to May 2012, 68 patients with intractable PHN receiving paravertebral adriamycin injection under CT guidance were enrolled. The outcome included the Quality of Life Score (QLS), Visual Analogue Score (VAS) (average, the worst and the least VAS), pain relief rate at the time before and after the injection, and 1 year after discharge. RESULTS: Lower VAS was observed after the injection than that before the injection [(3.5 ± 1.5) vs (7.9 ± 1.3) on average; (2.1 ± 0.9) vs (6.5 ± 1.7) at least and (4.5 ± 1.4) vs (9.2 ± 1.1) at worst, P<0.05]. Lower VAS at 1 year after discharge was found than that before the injection [(2.2 ± 1.8) vs (7.9 ± 1.3) on average; (1.5 ± 0.8) vs (6.5 ± 1.7) at least; (3.2 ± 1.6) vs (9.2 ± 1.1) at worst ] and that after the injection [(3.5 ± 1.5) vs (2.2 ± 1.8) on average; (1.5 ± 0.8) vs (2.1 ± 0.9) at least and (3.2 ± 1.6) vs (4.5 ± 1.4) at worst, P<0.05]. The pain relief rate after the injection was (68 ± 23)%. The pain relief rate at 1 year after discharge (81 ± 22)% was higher than that at discharge (68 ± 23)% (P<0.05). The quality of life evaluation index scale after the injection (daily life, diet, general activities, sleep, work and social activities) was significantly improved than that before the injection [(10.1 ± 2.2) vs (14.2 ± 1.9), P<0.05]. The quality of life evaluation index scale at 1 year after discharge was significantly improved than that before the injection [(7.0 ± 2.1) vs (14.2 ± 1.9)] and that after the injection [(7.0 ± 2.1) vs (10.1 ± 2.2), P<0.05]. No complication was observed when the patients were discharged and 1 year after discharge. CONCLUSION Paravertebral adriamycin injection under CT guidance for intractable PHN can effectively relieve the patient's pain, improve the quality of sleep and life without obvious complications. It is safe and effective for intractable PHN.
Doxorubicin ; administration & dosage ; therapeutic use ; Humans ; Neuralgia, Postherpetic ; drug therapy ; Pain Measurement ; Quality of Life

We evaluated the prophylactic efficacy of intravesical irrigation with distilled water immediately after transurethral resection(IUR) of superficial bladder tumor patients. Control group(n=30), with normal saline irrigation immediately after TUR(=15 min.) and continuous intravesical instillation of adriamycin 150mg with 3000ml normal saline for 2 days postoperatively. Distilled water group(n=28), with the same modality as control group, except for distilled water as the irrigation solution. The overall recurrence rates were 35.7% in distilled water group, which were more effective than 60.0% in control group. The 2 yeas tumor free rates by Kaplan-Meier method was higher in distilled water group ( 71.4% ) than control group (46.4% ), respectively with statistical significance. But, the mean time to recurrence were 13.3 months in control group and 14.1 months in distilled water group, without significant differences between two groups. These results support that the reasonable benefits of distilled water for prophylaxis of recurrence in superficial bladder tumor.
Administration, Intravesical ; Doxorubicin ; Humans ; Recurrence ; Urinary Bladder Neoplasms* ; Urinary Bladder* ; Water*

OBJECTIVETo develop polyethylenimine-Doxorubicin-montmorillonite (PEI-Dox-MTT) as a novel multifunction delivery system.

METHODSDox was intercalated into montmorillonite, PEI covered to the surface of Dox/MMT to make the nano-particle. XRD, FT-IR and TGA were used to confirm chemical property of the nano-particle. SEM was used to observe the morphology. The capability of drug release was investigated by PBS buffer solution (pH 7.4). The DNA binding ability of nano-particle was detected by gel electrophoresis retardation assay. The cell viability in COS-7 and SKOV3 cell lines was tested using MTT assay. The gastric mucosa protection was evaluated in vitro.

RESULTSXRD image showed that Dox was intercalated into montmorillonite, inter space of which increased to 31.3Å; the FT-IR spectra showed the vibration bands of PEI at 1 560 cm(-1) and 2 850 cm(-1), the vibration band of Dox at 1 350 cm(-1). Size analysis and SEM revealed that the size of nano-particle was 600 nm, and the zeta-potential was 30 mV. Drug release experiment explored that the nano-particle stably released drug in range of 6 X10(-4) ≊ 8 X10(-4) mg/ml within 72 h. MTT assay showed that the cell viability was over 80% in experiment condition in COS-7 and SKOV3 cell lines. 0.3 mg PEI-MMT nano-particle was able to protect gastric mucosa from alcohol.

CONCLUSIONMultifunction system of PEI/Dox/MMT has been prepared successfully.

Bentonite ; Cell Line ; Doxorubicin ; administration & dosage ; Drug Delivery Systems ; Genetic Vectors ; Humans ; Polyethyleneimine

OBJECTIVE: To prepare ion exchange doxorubicin-loaded poly (acrylic acid) microspheres (DPMs) and evaluate the properties of these chemoembolic agents. METHODS: Poly (acrylic acid) microspheres (PMs) without drug were prepared by inverse suspension polymerization method and then doxorubicin was loaded by ion exchange mechanism to prepare DPMs. Optical microscope was used to investigate the morphology and particle size distribution of PMs and DPMs; fluorescence microscope and confocal microscope were used to observe the distribution of doxorubicin after drug loading. Elasticities of both the microspheres were evaluated by texture analyzer. High performance liquid chromatography (HPLC) method was established to determine the drug loading behavior of PMs and releasing behavior of DPMs. The in vivo embolic property was evaluated by embolizing the hepatic artery of a rabbit with 0.1 mL of DPMs. RESULTS: PMs and DPMs were both spherical in shape, smooth in surface and dispersed well. Doxorubicin was mainly in the outer area inside of DPMs and distributed evenly. The average particle size of PMs and DPMs were (283±136) μm and (248±149) μm, respectively. PMs and DPMs both had good compression ability with the Young's modulus of (62.63±1.65) kPa and (93.94±1.10) kPa separately. PMs reached the drug loading balance at 12 h, and the entrapment efficiency was greater than 99%. Drug loading of PMs in doxorubicin solution at the concentration of 5.0 g/L and 12.5 g/L was (19.78±0.27) g/L and (49.45±0.37) g/L, respectively. Doxorubicin released slowly from DPMs in PBS and the accumulative release percentages of DPMs with corresponding drug loading were 6.82%±0.02% and 2.83%±0.10% after 24 h, respectively. Arterial angiograms showed that the hepatic artery of the rabbit was successfully embolized with DPMs. CONCLUSION DPMs with good performance of loading doxorubicin could be a potential embolic agent for transcatheter arterial chemoembolization.
Acrylates ; Animals ; Doxorubicin/administration & dosage* ; Embolization, Therapeutic/methods* ; Microspheres ; Particle Size ; Rabbits