1.Liver targeting and the delayed drug release of the nanoparticles of adriamycin polybutylcyanoacrylate in mice.
Liang-fang SHEN ; Yang-de ZHANG ; Hai-ju SHEN ; Shan ZENG ; Xin WANG ; Cheng WANG ; Yuan LE ; Hong SHEN
Chinese Medical Journal 2006;119(15):1287-1293
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
2.Preparation of paclitaxel-loaded polybutylcyanoacrylate nanoparticles.
Ru-da CHEN ; Fei REN ; Guo-feng LI ; Si-jia LIU
Journal of Southern Medical University 2010;30(4):763-766
OBJECTIVETo evaluate the effect of different preparation methods on the encapsulation efficiency (EE) and drug loading (DL) of paclitaxel-loaded polybutylcyanoacrylate nanoparticles (PTX-PBCA-NPs) and optimize the preparation of PTX-PBCA-NPs.
METHODSWith DL and EE as the major indexes, the qualities of PTX-PBCA-NPs produced by the interfacial polymerization and emulsion polymerization method were compared. The optimized prescription was obtained by orthogonal design.
RESULTSThe ranges of EE of PTX-PBCA-NPs with the two methods were both 94.39%-99.23%. The highest DL with interfacial polymerization was (1.07-/+0.03)%, as compared to (0.86-/+0.01)% with emulsion polymerization. The optimized preparation conditions resulted in the mean size of PTX-PBCA-NPs of 235.6 nm, DL of 0.80%, and EE of 95.71%.
CONCLUSIONThe EE of PTX-PBCA-NPs prepared by the above two methods is consistent with the requirement of the Pharmacopoeia of China, and PTX-PBCA-NPs containing higher DL can be obtained via interfacial polymerization.
Delayed-Action Preparations ; chemical synthesis ; Drug Carriers ; chemistry ; Drug Delivery Systems ; Enbucrilate ; chemistry ; Nanoparticles ; chemistry ; Paclitaxel ; administration & dosage ; Polymerization
3.Percutaneous Transportal Sclerotherapy with N-Butyl-2-Cyanoacrylate for Gastric Varices: Technique and Clinical Efficacy.
Korean Journal of Radiology 2008;9(6):526-533
OBJECTIVE: This study was deigned to evaluate the technique and clinical efficacy of the use of percutaneous transportal sclerotherapy with N-butyl-2-cyanoacrylate (NBCA) for patients with gastric varices. MATERIALS AND METHODS: Seven patients were treated by transportal sclerotherapy with the use of NBCA. For transportal sclerotherapy, portal vein catheterization was performed with a 6-Fr sheath by the transhepatic approach. A 5-Fr catheter was introduced into the afferent gastric vein and a microcatheter was advanced through the 5-Fr catheter into the varices. NBCA was injected through the microcatheter in the varices by use of the continuous single-column injection technique. After the procedure, postcontrast computed tomography (CT) was performed on the next day and then every six months. Gastroendoscopy was performed at one week, three months, and then every six months after the procedure. RESULTS: The technical success rate of the procedure was 88%. In six patients, gastric varices were successfully obliterated with 1-8 mL (mean, 5.4 mL) of a NBCA-Lipiodol mixture injected via a microcatheter. No complications related to the procedure were encountered. As seen on the follow-up endoscopy and CT imaging performed after six months, the presence of gastric varcies was not seen in any of the patients after treatment with the NBCA-Lipiodol mixture and the use of microcoils. Recurrence of gastric varices was not observed during the follow-up period. Worsening of esophageal varices occurred in four patients after transportal sclerotherapy. The serum albumin level increased, the ammonia level decreased and the prothrombin time increased at six months after the procedure (p < 0.05). CONCLUSION: Percutaneous transportal sclerotherapy with NBCA is useful to obliterate gastric varices if it is not possible to perform balloon-occluded retrograde transvenous obliteration.
Aged
;
Catheterization
;
Contrast Media/administration & dosage
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Enbucrilate/*administration & dosage
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Esophageal and Gastric Varices/radiography/*therapy
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Female
;
Fluoroscopy
;
Humans
;
Iodized Oil/administration & dosage
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Male
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Middle Aged
;
Portal Vein
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Sclerotherapy/*methods
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Tissue Adhesives/*administration & dosage
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Tomography, X-Ray Computed
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Ultrasonography, Interventional
4.Ethanol Embolotherapy of Pelvic Arteriovenous Malformations: an Initial Experience.
Sooho BAE ; Young Soo DO ; Sung Wook SHIN ; Kwang Bo PARK ; Dong Ik KIM ; Young Wook KIM ; Sung Ki CHO ; Sung Wook CHOO ; In Wook CHOO
Korean Journal of Radiology 2008;9(2):148-154
OBJECTIVE: We retrospectively assessed the results of performing ethanol embolization for pelvis arteriovenous malformations (AVMs). MATERIALS AND METHODS: During the past 10 years, eight patients (8 females, age range: 27-52 years) with AVMs in the pelvic wall (n = 3) and uterus (n = 5) underwent staged ethanol embolizations (range: 1-5, mean: 2.5) under general anesthesia. Ethanol embolization was performed by the use of the transcatheter and/or direct puncture techniques. Clinical follow-up was performed for all of the patients, and imaging follow-up was available for seven patients. The therapeutic outcomes were established by evaluating the clinical outcome of the signs and symptoms, as well as the degree of devascularization observed on post-procedural angiography. RESULTS: During the 20 sessions of ethanol embolization, the solitary transarterial approach was used 14 times, the transvenous approach was used three times and direct puncture was used once. For two patients, the transarterial and transvenous or direct puncture approaches were used together in one session. For four patients, ethanol and coils were used as embolic agents, and n-butyl cyanoacrylate (NBCA) and ethanol were used in one patient. Seven (88%) of eight patients were cured of their AVMs and one patient (12%) displayed improvement. Major complications were seen in two patients (25%). CONCLUSION: Ethanol embolization is effective for the treatment of pelvic arteriovenous malformations, though there is a chance of a major complication.
Adult
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Arteriovenous Malformations/*therapy
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Embolization, Therapeutic/adverse effects/*methods
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Enbucrilate/administration & dosage
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Ethanol/administration & dosage
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Female
;
Humans
;
Middle Aged
;
Pelvis/*blood supply
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Retrospective Studies
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Solvents/administration & dosage
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Tissue Adhesives/administration & dosage
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Uterus/*blood supply
5.Stroke from Delayed Embolization of Polymerized Glue Following Percutaneous Direct Injection of a Carotid Body Tumor.
Thamburaj KRISHNAMOORTHY ; Arun Kumar GUPTA ; Jayadevan E RAJAN ; Bejoy THOMAS
Korean Journal of Radiology 2007;8(3):249-253
A 52-year-old male with right carotid body tumor underwent direct percutaneous glue (n-butylcyanoacrylate [NBCA]) embolization. Several hours later, he developed left hemiparesis from embolization of the polymerized glue cast. Migration of glue during percutaneous tumor embolization is presumed to occur only in the liquid state, which may lead to stroke or cranial nerve deficits. To the best of our knowledge, this is the first report of delayed glue embolization from a treated hypervascular tumor of the head and neck.
Carotid Body Tumor/blood supply/*therapy
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Cyanoacrylates/administration & dosage/*adverse effects
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Embolization, Therapeutic/*methods
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Enbucrilate
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Foreign-Body Migration/*complications
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Humans
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Injections, Intralesional
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Male
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Middle Aged
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Stroke/*etiology
6.Transcatheter Arterial Embolization of Arterial Esophageal Bleeding with the Use of N-Butyl Cyanoacrylate.
Ji Hoon PARK ; Hyo Cheol KIM ; Jin Wook CHUNG ; Hwan Jun JAE ; Jae Hyung PARK
Korean Journal of Radiology 2009;10(4):361-365
OBJECTIVE: To evaluate the clinical efficacy and safety of a transcatheter arterial embolization (TAE) with N-butyl cyanoacrylate (NBCA) for the treatment of arterial esophageal bleeding. MATERIALS AND METHODS:Between August 2000 and April 2008, five patients diagnosed with arterial esophageal bleeding by conventional angiography, CT-angiography or endoscopy, underwent a TAE with NBCA. We mixed NBCA with iodized oil at ratios of 1:1 to 1:4 to supply radiopacity and achieve a proper polymerization time. After embolization, we evaluated the angiographic and clinical success, recurrent bleeding, and procedure-related complications. RESULTS: The bleeding esophageal artery directly originated from the aorta in four patients and from the left inferior phrenic artery in one patient. Although four patients had an underlying coagulopathy at the time of the TAE, angiographic and clinical success was achieved in all five patients. In addition, no procedure-related complications such as esophageal infarction were observed during this study. CONCLUSION: NBCA can be an effective and feasible embolic agent in patients with active arterial esophageal bleeding, even with pre-existing coagulopathy.
Adult
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Aged
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Angiography
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Arteries
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Catheterization
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Embolization, Therapeutic/*methods
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Enbucrilate/administration & dosage/*therapeutic use
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Esophageal Diseases/radiography/*therapy
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Female
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Gastrointestinal Hemorrhage/radiography/*therapy
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Humans
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Male
;
Middle Aged
7.Percutaneous Transabdominal Approach for the Treatment of Endoleaks after Endovascular Repair of Infrarenal Abdominal Aortic Aneurysm.
Sun Young CHOI ; Jong Yun WON ; Do Yun LEE ; Donghoon CHOI ; Won Heum SHIM ; Kwang Hun LEE
Korean Journal of Radiology 2010;11(1):107-114
OBJECTIVE: The purpose of this study was to evaluate the technical feasibility and clinical efficacy of percutaneous transabdominal treatment of endoleaks after endovascular aneurysm repair. MATERIALS AND METHODS: Between 2000 and 2007, six patients with type I (n = 4) or II (n = 2) endoleaks were treated by the percutaneous transabdominal approach using embolization with N-butyl cyanoacrylate with or without coils. Five patients underwent a single session and one patient had two sessions of embolization. The median time between aneurysm repair and endoleak treatment was 25.5 months (range: 0-84 months). Follow-up CT images were evaluated for changes in the size and shape of the aneurysm sac and presence or resolution of endoleaks. The median follow-up after endoleak treatment was 16.4 months (range: 0-37 months) RESULTS: Technical success was achieved in all six patients. Clinical success was achieved in four patients with complete resolution of the endoleak confirmed by follow-up CT. Clinical failure was observed in two patients. One eventually underwent surgical conversion, and the other was lost to follow-up. There were no procedure-related complications. CONCLUSION: The percutaneous transabdominal approach for the treatment of type I or II endoleaks, after endovascular aneurysm repair, is an alternative method when conventional endovascular methods have failed.
Aged
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Aged, 80 and over
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Aortic Aneurysm, Abdominal/*surgery
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*Blood Vessel Prosthesis Implantation
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Embolization, Therapeutic/*methods
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Enbucrilate/*administration & dosage
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Female
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Humans
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Male
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Middle Aged
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Postoperative Complications/*therapy
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Punctures
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*Stents
8.Observe the curative effect of n-Butyl cyanoacrylate injection in treating laryngopharynx hemangioma.
Weimin LI ; Bo FENG ; Jialing WANG ; Wenming WU ; Liangfa LIU ; Rongguang WANG ; Dongyan HUANG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2008;22(24):1120-1122
OBJECTIVE:
To evaluate the clinical effectiveness of injection n-Butyl cyanoacrylate (NBCA) in treating laryngopharynx hemangioma.
METHOD:
Thirty cases of laryngopharynx hemangioma who received NBCA injection were obtained from our department 1998-2007. Twenty-five cases had tracheotomy under General anesthesia, and NBCA was injected into hemangioma by direct laryngoscopy. NBCA was mixed with iodide, and the concentration was 25.00% to 33.33%, NBCA dosage was 0.5 ml to 2.0 ml. There were 5 cases whose hemangioma confined to oropharynx didn't have tracheotomy, and they were injected straightly with the speculum oris. We observed the shedding of hemangioma in different time.
RESULT:
Hemangioma with diameter less than 1 cm, shedded in about 1 month. However, hemangioma with diameter more than 4 cm, shedded in a period more than 3.5 month. No recurrence was observed in the follow up of 3 months to seven years.
CONCLUSION
Avoiding dissection of neck and repetitious operation, NBCA injection could be a safe, simple and effective therapy for laryngopharynx hemangioma.
Adolescent
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Adult
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Aged
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Child
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Embolization, Therapeutic
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Enbucrilate
;
administration & dosage
;
therapeutic use
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Female
;
Hemangioma
;
therapy
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Humans
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Laryngoscopy
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Male
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Middle Aged
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Pharyngeal Neoplasms
;
therapy
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Treatment Outcome
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Young Adult
9.Cyst Ablation Using a Mixture of N-Butyl Cyanoacrylate and Iodized Oil in Patients with Autosomal Dominant Polycystic Kidney Disease: the Long-Term Results.
See Hyung KIM ; Seung Hyup KIM ; Jeong Yeon CHO
Korean Journal of Radiology 2009;10(4):377-383
OBJECTIVE: We wanted to assess the long-term results of cyst ablation with using N-butyl cyanoacrylate (NBCA) and iodized oil in patients with autosomal dominant polycystic kidney disease (ADPKD) and symptomatic cysts. MATERIALS AND METHODS:Cyst ablation using a mixture of NBCA and iodized oil was performed in 99 cysts from 21 patients who had such symptoms as abdominal distension and pain. The collapse or reaccumulation of the ablated cysts after the procedure was assessed during the follow-up period of 36 to 90 months. The treatment effects, including symptom relief, and the clinical data such as the blood pressure and serum creatinine levels were also assessed, together with the complications. RESULTS: The procedure was technically successful in all 99 cysts from the 21 patients. Any procedure-related significant complications were not detected. Seventy-seven of 99 cysts (78%) were successfully collapsed on the follow-up CT. Twenty-two cysts showed reaccumulation during long-term follow-up period. The clinical symptoms were relieved in 17 of the 21 patients (76%). Four of 12 patients (33%) with hypertension and two of six patients (33%) with azotemia were improved. End stage renal disease (ESRD) occurred in six of the 21 patients (28%) during the follow-up period. The mean age of ESRD in our patients was 57 years. The mean time interval for the development of ESRD was 19 months. CONCLUSION: Ablation using a mixture of NBCA and iodized oil may be an effective, safe method for obtaining symptom relief in patients with ADPKD.
Adult
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Aged
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Enbucrilate/administration & dosage/*therapeutic use
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Female
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Follow-Up Studies
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Humans
;
Iodized Oil/administration & dosage/*therapeutic use
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Male
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Middle Aged
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Polycystic Kidney, Autosomal Dominant/*surgery
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Sclerosing Solutions/administration & dosage/*therapeutic use
10.Effect of diameter of adriamycin polybutylcyanoacrylate nanoparticles on liver targeting.
Liang-fang SHEN ; Xin WANG ; Cheng WANG ; Kai ZHAO ; Xin-ju LIU ; Hai-ju SHEN
Journal of Central South University(Medical Sciences) 2006;31(5):732-741
OBJECTIVE:
To observe the different tissue distributions of the adriamycin polybutylcyanoacrylate nanoparticle (ADM-PBCA-NP) in the mice body after the injection via lateral tail vein, and to study the liver targeting effects of ADM-PBCA-NP in different diameters on normal mice livers.
METHODS:
One hundred and eighty mice were randomly divided into 6 groups with 30 mice in each group: non-conjugated free ADM (Group 1); (22.3+/-6.2) nm in diameter ADM-PBCA-NP group (Group 2); (48.6+/-9.2) nm ADM-PBCA-NP group (Group 3); (101.9+/-20.3) nm ADM-PBCA-NP group (Group 4); (143.5+/-23.5) nm ADM-PBCA-NP group (Group 5), and (194.2+/-28.4) nm ADM-PBCA-NP group (Group 6). 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 after the injection, respectively. The adriamycin concentrations in the collected livers, kidneys, spleens, hearts, lungs and plasma were demonstrated using a high performance liquid chromatography with fluorescence detector.
RESULTS:
Compared with that of the control group, adriamycin was hardly detected in the heart muscles of the treatment groups (P<0.05). The nanoparticle-conjugated adriamycin was cleaned up quickly from the kidney tissues. The adriamycin concentrations of the mice liver and spleen in the experimental groups was significantly higher than those 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 (101.9+/-20.3) nm diameter had the highest liver distribution, and the second highest adriamycin distribution in the liver was the group of (143.5+/-23.5) nm diameter (P<0.05). 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 tissues of the livers, kidneys, hearts, spleens, and lungs.
CONCLUSION
ADM-PBCA-NP with a 100 - 150 nm diameter range has the best liver targeting with slow medicine release. It also decreases the medicine distribution in the heart and other organs. In the treatment of liver cancer, the polybutylcyanoacrylate nanoparticle system has a good liver targeting ability, which increases the anticancer activity and markedly decreases the toxicity of adriamycin.
Animals
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Antibiotics, Antineoplastic
;
administration & dosage
;
pharmacokinetics
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Doxorubicin
;
administration & dosage
;
pharmacokinetics
;
Drug Carriers
;
Drug Delivery Systems
;
Enbucrilate
;
administration & dosage
;
pharmacokinetics
;
Liver
;
metabolism
;
Male
;
Mice
;
Nanoparticles
;
Particle Size
;
Random Allocation
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Tissue Distribution