Drug-eluting Microspheres Research Articles

A review of conventional and drug-eluting chemoembolization in the treatment of colorectal liver metastases: principles and proof.

The management of colorectal liver metastasis has undergone a significant change since the development of novel ablation and embolization. Drug-eluting microsphere platforms, designed to deliver targeted concentrations of systemic therapy directly into the tumor via its arterial vasculature, have garnered interest and gained in popularity in recent years. Based on in vitro and in vivo data, multiple factors contribute to locoregional exposure including carrier base, smaller particle size (larger surface area), chemotherapeutic and chemotherapeutic intensity. Based on the current published clinical data, therapy appears well tolerated but the questions remain as to the ideal technique, patient population and overall efficacy. The purpose of this article is to provide a perspective on the scientific basis, and clinical review of the current data supporting the use of this platform in the setting of metastatic colorectal carcinoma.

Preparation and structure of drug-carrying biodegradable microspheres designed for transarterial chemoembolization therapy

Biodegradable poly(D,L-lactic acid) drug-eluting microspheres containing anti-tumor drugs, cisplatin, and sorafenib tosylate have been prepared by the emulsion solvent evaporation method with diameter between 200 and 400 μm. Scanning electron microscopy showed that cisplatin microspheres had smooth surfaces, while sorafenib tosylate microspheres and cisplatin + sorafenib tosylate microspheres were porous at the surface and the pits of the latter were larger than those of the former. Notably, cisplatin + sorafenib tosylate microspheres had a fast drug release rate compared with microspheres containing one drug alone. In vitro cytotoxicity experiments and classical matrigel endothelial tube assay certificated the maintaining bioactivity of cisplatin and sorafenib tosylate released from the microspheres, respectively. This work provides a useful approach for the fabrication of drug-eluting beads used in transarterial chemoembolization.

Sunitinib-eluting beads for chemoembolization: Methods for in vitro evaluation of drug release

Drug-eluting microspheres are used for embolization of hypervascular tumors and allow for local controlled drug release. Although the drug release from the microspheres relies on fast ion-exchange, so far only slow-releasing in vitro dissolution methods have been correlated to in vivo data. Three in vitro release methods are assessed in this study for their potential to predict slow in vivo release of sunitinib from chemoembolization spheres to the plasma, and fast local in vivo release obtained in an earlier study in rabbits. Release in an orbital shaker was slow (t50%=4.5h, 84% release) compared to fast release in USP 4 flow-through implant cells (t50%=1h, 100% release). Sunitinib release in saline from microspheres enclosed in dialysis inserts was prolonged and incomplete (t50%=9days, 68% release) due to low drug diffusion through the dialysis membrane. The slow-release profile fitted best to low sunitinib plasma AUC following injection of sunitinib-eluting spheres. Although limited by lack of standardization, release in the orbital shaker fitted best to local in vivo sunitinib concentrations. Drug release in USP flow-through implant cells was too fast to correlate with local concentrations, although this method is preferred to discriminate between different sphere types.

Chemoembolization with drug-eluting microspheres (DEM-TACE) for hepatocellular carcinoma: single-center review of safety and efficacy.

PurposeThis study examines the safety and efficacy of transarterial chemoembolization using doxorubicin-loaded 30–60 µm QuadraSphere microspheres (DEM-TACE) for the treatment of hepatocellular carcinoma.Materials and methodsOver 10 weeks, patients with hepatocellular carcinoma. (Child–Pugh A/B: 65%/35%) were embolized with 30–60 µm QuadraSphere microspheres. Excluded patients had previous locoregional therapy, macrovascular invasion, extrahepatic disease, Child–Pugh score >B7, ECOG performance status >0, and total bilirubin >3 mg/dL. Technical success, minor and major complications, 30-day hospital readmission rate, and 30-day mortality were assessed. α-Fetoprotein levels before and after treatment were compared. Local response was evaluated by radiologic tumor response per modified Response Evaluation Criteria in Solid Tumors 1 month after treatment.ResultsThirty tumors (mean size, 2.3 cm; range, 1.0–4.9 cm) were treated in 20 patients (16 male and 4 female; mean age, 64.7 years). There were no major complications. Thirty-day mortality was 0%. Minor complications included postembolization syndrome in 16.7% of cases and transient rise in liver enzymes requiring no therapy. Mean α-fetoprotein levels trended down following treatment (71.8±201.9 ng/mL vs 53.4±116.7 ng/mL), but were not statistically significant. Complete response was achieved in 30% of patients, partial response in 35%, stable disease in 30%, and progression of disease in 5%. Overall objective response was 65%. Mean follow-up was 10.4 months (range, 2–16.4 months).ConclusionDEM-TACE with doxorubicin-loaded 30–60 µm QuadraSpheres is feasible, well tolerated, and associated with promising tumor response in early and intermediate stage disease.

Pharmacokinetics and Antitumor Efficacy of Chemoembolization Using 40 µm Irinotecan-Loaded Microspheres in a Rabbit Liver Tumor Model

PurposeTo evaluate the pharmacokinetics and antitumor efficacy of 40 μm irinotecan-loaded drug-eluting microspheres (Embozene TANDEM Microspheres; CeloNova BioSciences, Inc, San Antonio, Texas) (TANDEM-IRI). Materials and MethodsThe following three groups included eight VX2 rabbits each: group 1, full-loaded (50 mg irinotecan/1 mL TANDEM)/high-dose injection (1 mg irinotecan/kg); group 2, full-loaded (50 mg irinotecan/1 mL TANDEM)/low-dose injection (0.5 mg irinotecan/kg); and group 3, half-loaded (25 mg irinotecan/1 mL TANDEM)/low-dose injection (0.5 mg irinotecan/kg). Irinotecan and SN-38 in the plasma and tumors were measured within 72 hours. Histologic examinations were conducted on days 1, 3, and 7. ResultsSerum irinotecan levels remained near the maximum concentration for 180 minutes after transarterial chemoembolization; in group 1, levels were 351.4 ng/mL at 30 minutes, 329.0 ng/mL at 60 minutes, and 333.5 ng/mL at 180 minutes. The area under the curve for 0–24 hours of irinotecan in group 1 was approximately two times higher than the same value in groups 2 and 3. High irinotecan and SN-38 concentrations in the tumors were measured at 24 hours and 72 hours. After transarterial chemoembolization, levels of liver enzymes aspartate aminotransferase and alkaline phosphatase were significantly higher in group 1 compared with groups 2 and 3. Histologic findings showed microspheres had deeply penetrated into tumors. Significantly higher tumor necrosis ratios were observed in groups 1 (86.6%–90.0%) and 3 (90.0%–100%) compared with group 2 (63.3%–70%) (P = .031 and P = .016). ConclusionsSlow drug release with high drug concentration in tumors can be provided with 40 μm TANDEM-IRI. When complete arterial embolization is performed, the dose of irinotecan loaded on 40 μm TANDEM microspheres can be reduced while maintaining efficacy.

Transarterial chemoembolization for hepatocellular carcinoma with drug-eluting microspheres

PurposeTo investigate the efficacy of transarterial chemoembolization (TACE) with microspheres (HepaSphere) loaded with doxorubicin in patients with hepatocellular carcinoma (HCC). Materials and methodsFrom April to December 2013, 50 patients with HCC were treated by selective TACE using HepaSphere microspheres loaded with doxorubicin. The size of the lesions was from 2 to 9cm (mean 5.2). ResultsAll of the procedures were technically successful, and there were no major complications. At 1-month follow-up, there was complete tumor response in 48%, partial response in 42%, stable disease in 10%, and there were no cases of disease progression. At 3-month follow-up, complete tumor response was observed in 42%, partial response in 38%, stable disease in 16%, and progressive disease in 4%. At 6-month follow-up, there was complete response in 40%, partial response in 36%, stable disease in 10% and progressive disease in 14%.Within the initial 6-month follow-up, TACE with HepaSphere was successfully repeated once in 3 patients, whereas 2 patients underwent the procedure twice. ConclusionChemoembolization using doxorubicin-loaded HepaSphere is a safe and effective treatment of HCC as demonstrated by the low complication rate, and increased tumor response. When complete tumor response is not achieved, additional treatments can be performed without difficulties.

Multidisciplinary management of hepatocellular carcinoma: a model for therapy

A multidisciplinary model is a useful approach in the management of hepatocellular carcinoma (HCC) to coordinate, individualize, and optimize care. The HCC Multidisciplinary Team (MDT) at Temple University Hospital was established in 2008 and comprises hepatologists, interventional radiologists, transplant surgeons, oncologists, residents, midlevel providers, and support staff. Patients may be enrolled by referral from (1) oncologists at Temple, (2) the hepatitis screening clinic recently established at Temple and staffed by hepatology residents, or (3) community practices. MDT conferences are held weekly, during which cases are discussed (based on medical history, interpretation of images, and laboratory analyses) and treatment plans are formulated. The Temple treatment algorithm follows current standards of care, guided by tumor volume and morphology, but the novel multidisciplinary interaction challenges members to tailor therapy to achieve the best possible outcomes. Patients with a solitary lesion ≤ 2 cm may receive no treatment until eligible for transplantation or locoregional therapy or resection, with imaging every 3 to 6 months to monitor tumor progression. In patients with tumors > 2 cm and ≤ 5 cm, microwave ablation therapy is used if lesions are discrete and accessible. Conventional transarterial chemoembolization (TACE) or drug-eluting bead TACE (DEB-TACE) or yttrium-90 microspheres are utilized in multifocal disease. Patients with lesions > 5 cm are candidates for TACE for downstaging the tumor. Sorafenib is typically reserved for unresectable lesions between 2 cm and 5 cm. Frequently, we administer sorafenib continuously and in combination with DEB-TACE. In our experience, sorafenib does not produce effects on the tumor vasculature or blood flow that would impair the efficacy of DEB-TACE. The literature documents improved outcomes in HCC and other cancers associated with the introduction of multidisciplinary care. The role and organization of the MDT is influenced by team culture, expertise, and process, as well as institutional and larger environmental contexts.

Abstract No. 410 - Safety of chemoembolization with drug-eluting microspheres (DEB-TACE) in patients with pre-existing transjugular intrahepatic portosystemic shunt (TIPS)

Purpose To assess the safety of DEB-TACE for inoperable hepatocellular carcinoma (HCC) in patients with pre-existing TIPS. Materials and Methods In this retrospective IRB approved study, we reviewed medical records of patients with a functioning TIPS who underwent DEB-TACE with doxorubicin (100mg) loaded LC beads for inoperable HCC between 2005 and 2011. Patient demographics, number of procedures, type of embolization (lobar, segmental), and post-procedure complications were recorded. The incidence of post-procedure liver failure, renal failure, duration of in-hospital stay, 30-day mortality and Grade 3 and 4 toxicity (NCCN V.3) were recorded. Results During this period, five patients (3Men, Mean age 64y) with a functioning TIPS underwent DEB-TACE for inoperable HCC. The number of procedures per patient ranged from 1-4, with a median of 1. Three patients had lobar embolization and the rest, segmental arterial embolization. Post-op stay ranged from 1-20days. During the 8 procedures, two procedures (in two different patients), two patients required prolonged admission to (max 20 days) for pain and edema. Both of them had lobar embolization. Grade 3 toxicity of AST, ALT, Bilirubin was seen in one patient. There were no deaths within 30 days of the procedure. None had renal failure. Conclusion DEB-TACE for HCC is well tolerated with minimal complications in patients with pre-existing TIPS. Complications leading to prolonged in-hospital course are more often seen in patients who received lobar embolization.

TACE with doxorubicin eluting beads (hepasphere™): results and comparison with historical personal series of standard TACE

Purpose To present our experience using HepaSphere™ microspheres (Biosphere Medical) loaded with Doxorubicin in patients with unresectable Hepatocellular Carcinoma and to compare this series with our precedent series of traditonal TACE: TACE with Lipiodol and Spongostan (340 pts treated from December 1991 to April 1996) and TACE with Lipiodol and Embosphere (46 pts treated from February 2000 to November 2005). Materials and Methods From December 2005 to June 2012, 165 patients (134 male, 31 female, mean age 71 years, medium follow-up 9-month) were treated by selective TACE using HepaSphere™ loaded with Doxorubicin. The diameter of the lesions ranged from 25 to 176 mm, with a mean diameter of 64.2 mm and a maximum of 4 lesions. Results Technical success rate was 100%, with complete devascularization of the lesions at the end of all procedures. One month CT follow-up shows complete necrosis (90-100%) of lesions in 39.4%, partial necrosis (50-89%) in 44,2%, and progression disease (0-49%) in 6.4%. 9 month follow-up shows complete necrosis in 26,6%, partial necrosis in 42.2% and progression disease in 19%; Survival at 12 months was 80.3% in HepaSphere™, 73.9% in Embosphere and 59.1% in Spongostan group; survival at 24 months was 72% in HepaSphere™ group. Conclusion Our experience demonstrates that TACE using HepaSphere™ is feasible, with low complication rate and promising efficacy. The results seem to be better than standard TACE with Embosphere and Gelfoam. Larger series and randomized studies are mandatory to confirm these preliminary results.

Chemoembolization and Radioembolization for Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) continues to represent a major worldwide problem. Although treatments such as resection, transplantation, and ablation may provide a chance for a cure, these options are often precluded because of advanced disease presentation. Palliative treatments include transarterial embolization and systemic therapies. This review will summarize the state of the science for embolic therapies in HCC (conventional and drug-eluting chemoembolization, radioembolization) as well as discuss related topics including HCC staging, assessment of response, and ongoing clinical trials.

Unresectable Lung Malignancy: Combination Therapy with Segmental Pulmonary Arterial Chemoembolization with Drug-eluting Microspheres and Radiofrequency Ablation in 17 Patients

To evaluate the feasibility, safety, and effectiveness of combining segmental pulmonary arterial chemoembolization (SPACE) and percutaneous radiofrequency (RF) ablation in patients with unresectable lung neoplasms or patients with resectable neoplasms who refused surgery and to compare the local tumor progression (LTP) rate with that in previous studies of RF ablation alone. After institutional review board approval and informed consent, 17 patients with primary and metastatic lung cancer were enrolled in this prospective study. Between January 2008 and February 2011, 20 nodules (median diameter, 3.0 cm; range, 2.0-5.0 cm) were treated during 19 sessions. Antineoplastic agents loaded on 50-100-µm microspheres were selectively infused into specific pulmonary arteries. Percutaneous computed tomography (CT)-guided RF ablation of lung nodules was performed 48 hours after SPACE. Follow-up consisted of enhanced CT 48 hours after combination treatment was completed, after 30 days, and every 3 months thereafter. Fluorine 18 fluorodeoxyglucose positron emission tomography was performed 3 months after combination therapy and then every 6 months. The t test was used to compare groups. Technical success was achieved in 100% of cases. Ventilation-lung single photon emission computed tomography showed a wide area without ventilation in the lung parenchyma treated with SPACE. The LTP rate was 21% (three of 14 nodules) in 3-5-cm-diameter tumors and 0% (zero of six nodules) in tumors of 3 cm or smaller in diameter. Complete response was achieved in 65% (11 of 17) of patients at minimum follow-up of 6 months. Overall, treatment was well tolerated. Major complications were pneumothorax in five of 19 sessions (26%) and one bronchopleural fistula (one of 19, 5%). No treatment-related changes in general lung function were noted. Combination therapy with RF ablation after SPACE to treat unresectable lung tumors is technically feasible, safe, and effective and may represent an advantage over RF ablation alone.

Acute lung injury following transcatheter hepatic arterial chemoembolization of doxorubicin-loaded LC beads in a patient with hepatocellular carcinoma

Transcatheter arterial chemoembolization (TACE) currently is being used as an effective palliative therapy for unresectable cancers especially hepatocelluar carcinoma (HCC). Accidental lipiodol embolism to the lungs is a rare but potentially fatal complication of TACE. This procedure involves injection of drug-eluting microspheres (LC Bead) loaded with doxorubicin, followed by embolization with embozene microspheres until stasis is evident, being used in advanced HCC. We report a patient with inoperable HCC with underlying Hepatitis C and liver cirrhosis, who developed acute lung injury following targeted chemoembolization of selective feeding hepatic artery with LC beads loaded with doxorubicin. Acute lung injury as a complication of unintended lung chemoembolization with doxorubicin has not been previously reported in the literature. Interventional radiologists screen patients for potential hepatic A-V shunt and take appropriate precautions to prevent unintended pulmonary embolization. These include appropriate selection of LC bead particle size especially in patients who are embolized with radiation pellets. This report highlights the need for a screening total body scintigraphy after injection of radionuclide Tc-99 MAA in the feeding hepatic artery to identify patients with hepatic A-V shunt. In such patients, appropriate size selection of LC bead particles is critical to prevent unintended pulmonary chemoembolization and acute lung injury. Other measures include careful patient selection, low dose of chemotherapy, and transient selective hepatic vein balloon occlusion.

Design and Fabrication of a High-Performance Electrochemical Glucose Sensor

Development of electrochemical sensors for continuous glucose monitoring is currently hindered by a variety of problems associated with low selectivity, low sensitivity, narrow linearities, delayed response times, hysteresis, biofouling, and tissue inflammation. We present an optimized sensor architecture based on layer stratification, which provides solutions that help address the aforementioned issues. The working electrode of the electrochemical glucose sensors is sequentially coated with five layers containing: (1) electropolymerized polyphenol (PPh), (2) glutaraldehyde-immobilized glucose oxidase (GOx) enzyme, (3) dip-coated polyurethane (PU), (4) glutaraldehyde-immobilized catalase enzyme, and (5) a physically cross linked polyvinyl alcohol (PVA) hydrogel membrane. The response of these sensors to glucose and electroactive interference agents (i.e., acetaminophen) was investigated following application of the various layers. Sensor hysteresis (i.e., the difference in current for a particular glucose concentration during ascending and descending cycles after 200 s) was also investigated. The inner PPh membrane improved sensor selectivity via elimination of electrochemical interferences, while the third PU layer afforded high linearity by decreasing the glucose-to-O2 ratio. The fourth catalase layer improved sensor response time and eliminated hysteresis through active withdrawal of GOx-generated H2O2 from the inner sensory compartments. The outer PVA hydrogel provided mechanical support and a continuous pathway for diffusion of various participating species while acting as a host matrix for drug-eluting microspheres. Optimal sensor performance has been achieved through a five-layer stratification, where each coating layer works complementarily with the others. The versatility of the sensor design together with the ease of fabrication renders it a powerful tool for continuous glucose monitoring.

Drug delivery embolization systems: a physician's perspective

Introduction: The number of patients suffering from primary and secondary liver tumoral diseases is on the increase worldwide. The development of new technologies and drugs requires an increasingly multidisciplinary approach in the management of these diseases. Therapies should be based on scientifically supported guidelines and at the same time should be designed to suit the individual patient. In this decision-making process, an understanding of the advantages and disadvantages of every treatment is very important. The efficacy of transarterial chemoembolization (TACE) in improving survival and its role in the management of hepatocellular carcinoma (HCC) have been demonstrated in several clinical trials. The introduction of drug-eluting beads seems to have overcome some of the limitations of conventional TACE.Areas covered: This review provides an overview of the spread of primary and secondary liver cancers, then it explains the basis for the use of conventional TACE and its potential benefits and, finally, outlines its clinical application and possible future uses.Expert opinion: The management of the treatment of focal liver lesions is a difficult process, which must involve various specialists such as the interventional radiologist. The use of drug-eluting microspheres seems to improve the results of TACE both in HCC and in colorectal liver metastases.

Current concepts in transarterial chemoembolization of hepatocellular carcinoma

Transarterial chemoembolization (TACE) has the potential to improve survival in patients with intermediate stage hepatocellular carcinoma (HCC). Careful selection of patients is mandatory to gain survival benefit and safe quality of life. Basic principles of TACE in HCC include selective treatment via intrahepatic and extrahepatic arteries, proper management of side effects and continuation of treatment guided by imaging. After conventional TACE, based on delivery of cytotoxic drugs emulsified in iodized oil and embolization of various types of particles, has been used for more than 20 years, the new concept of drug-eluting microspheres has been introduced. This technology effectively combines enhanced local drug delivery and ischemic embolization effects. Clinical studies showed intensified local necroses and reduced systemic toxic side effects compared to conventional TACE. Embolization of HCC with sub-100 μm particles penetrating deeply into the tumor vascular bed is another promising new option. Very effective devascularization of HCC nodules has been shown after 40 μm bland embolizations, however, potential risks like passage of particles into hepatic veins and systemic circulation have to be considered. Today the indication for TACE in intermediate stage HCC patients is widely accepted; however, there is no clear methodical standard so far. Further studies are necessary to define how to adapt various available methods to individual HCC and patients characteristics.

Switching the Loaded Agent from Epirubicin to Cisplatin: Salvage Transcatheter Arterial Chemoembolization with Drug-eluting Microspheres for Unresectable Hepatocellular Carcinoma

There is no consensus on switching anticancer agents loaded onto drug carriers in transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). This study aimed to evaluate the safety and clinical outcomes of TACE with cisplatin-loaded microspheres (CLM-TACE) in HCC patients refractory to TACE with epirubicin-loaded microspheres (ELM-TACE). Between February 2008 and June 2010, 85 patients with unresectable HCC refractory to ELM-TACE were enrolled to undergo CLM-TACE. The number of ELM-TACE sessions until judgment of resistance ranged from 1 to 4 (median, 2.1). CLM-TACE was performed using 50-100-μm superabsorbent polymer microspheres loaded with 1mg cisplatin/1mg microspheres together with hepatic arterial infusion of 25mg cisplatin and 500mg 5-fluorouracil per patient. Tumor responses were evaluated by computed tomography according to the European Association for the Study of the Liver criteria. The median number of CLM-TACE treatment sessions was 1.8 (range, 1-5), and the mean total dose of cisplatin per session was 42.8mg (range, 30.0-59.0). After 6months, 3 (3.5%) patients achieved complete response, 31 (36.5%) had partial response, 15 (17.6%) had stable disease, and 36 (42.4%) had progressive disease. The median overall survival and time to treatment failure after initial CLM-TACE were 13.3 and 7.2months, respectively. Overall, 9.4% of patients experienced grade 3/4 adverse events. Switching the loaded agent from epirubicin to cisplatin is a safe, well-tolerated, and efficacious treatment strategy for salvage TACE with drug-eluting microspheres in HCC patients refractory to ELM-TACE.

Abstract No. 173: Embolic load and dose of doxorubicin in the treatment of hepatocellular carcinoma utilizing drug-eluting superabsorbent polymer microspheres: Phase II trial of radiological/histopathological correlation of treatment and response

Abstract No. 173: Embolic load and dose of doxorubicin in the treatment of hepatocellular carcinoma utilizing drug-eluting superabsorbent polymer microspheres: Phase II trial of radiological/histopathological correlation of treatment and response

Trans-arterial chemo-embolization (TACE), with either lipiodol (traditional TACE) or drug-eluting microspheres (precision TACE, pTACE) in the treatment of hepatocellular carcinoma: efficacy and safety results from a large mono-institutional analysis

More data about TACE and pTACE seem necessary to better define the global treatment strategy for HCC. Aim of our analysis was to evaluate the role of TACE, either with lipiodol (traditional) or drug-eluting microspheres in terms of response rate (RR), time to progression (TTP), overall survival (OS) and toxicity in HCC.Patients with HCC undergoing traditional TACE or pTACE (either alone or in combination with other treatment options) were eligibleOne hundred and fifty patients were analyzed. In the global patient population median OS was 46 months for lipiodol TACE and 19 months for pTACE (p < 0.0001), TTP was 30 months versus 16 months for patients receiving TACE or pTACE respectively (p = 0.003). These results were confirmed also among the group of patients who received exclusive TACE or pTACE. Neither RR nor toxicity was different between TACE or pTACE.At multivariate analysis, age, the Okuda stage, type of TACE and number of TACE proved to be independent prognostic factors influencing overall survival.In our experience, lipiodol TACE showed a better OS and TTP over pTACE, without difference in toxicity profile and RR. Among the staging systems analyzed only the Okuda stage seemed able to reliably predict patients outcome.

Acute Thrombocytopenia: An Unusual Complication Occurring After Drug-Eluting Microspheres Transcatheter Hepatic Chemoembolization

Image-guided transcatheter hepatic chemoembolization (TACE) is accepted worldwide as an effective treatment for patients with unresectable hepatocellular carcinoma and liver metastases from neuroendocrine tumors, colorectal carcinomas, and uveal melanomas. Although the technique is relatively safe, it has been associated with several complications. We report the cases of two patients with colorectal liver metastases who developed acute thrombocytopenia a few hours after TACE. To our knowledge, acute thrombocytopenia occurring after TACE with drug-eluting microspheres has not yet been reported. Here we discuss the hypothetical etiopathogenetic mechanisms.

Comparative Study of Chemoembolization Loadable Beads: In vitro Drug Release and Physical Properties of DC Bead and Hepasphere Loaded with Doxorubicin and Irinotecan

To characterize in vitro the loadability, physical properties, and release of irinotecan and doxorubicin from two commercially available embolization microspheres. DC Bead (500-700 microm) and Hepasphere (400-600 microm) microspheres were loaded with either doxorubicin or irinotecan solutions. Drug amount was quantified with spectrophotometry, bead elasticity was measured under compression, and bead size and loading homogeneity were assessed with microscopy image analysis. Drug release was measured over 1-week periods in saline by using a pharmacopeia flow-through method. Almost complete drug loading was obtained for both microsphere types and drugs. Doxorubicin-loaded DC Beads maintained their spherical shape throughout the release. In contrast, Hepaspheres showed less homogeneous doxorubicin loading and, after release, some fractured microspheres. Incomplete doxorubicin release was observed in saline over 1 week (27% +/- 2 for DC beads and 18% +/- 7 for Hepaspheres; P = .013). About 75% of this amount was released within 2.2 hours for both beads. For irinotecan, complete release was obtained for both types of beads, in a sustained manner over 2-3 hours for DC Beads, and in a significantly faster manner as a 7-minute burst for Hepaspheres. The two drug-eluting microspheres could be efficiently loaded with both drugs. Incomplete doxorubicin release was attributed to strong drug-bead ionic interactions. Weaker interactions were observed with irinotecan, which led to faster drug release.