Calcium alginate beads as a slow‐release system for delivering angiogenic molecules In Vivo and In Vitro

Downs, Elizabeth C.; Robertson, Nancy E.; Riss, Terry; Plunkett, Marian L.

doi:10.1002/jcp.1041520225

Cited by 139 publications

(63 citation statements)

References 35 publications

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“…This delivery system allows prolonged (4 to 6 weeks) sustained release (first-order kinetics). 8,10,23 In animal studies, there was a dose-dependent effect of bFGF that was not associated with detectable serum levels, hemodynamic effects, or local or systemic toxicity. 5,8 Of the 46 patients judged to have a major coronary artery that could not be grafted on the basis of angiographic appearance, 22 patients were actually successfully grafted at the time of CABG.…”

Section: Discussionmentioning

confidence: 99%

Local Perivascular Delivery of Basic Fibroblast Growth Factor in Patients Undergoing Coronary Bypass Surgery

et al. 1999

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Background —Angiogenesis is a promising treatment strategy for patients who are not candidates for standard revascularization, because it promotes the growth of new blood vessels in ischemic myocardium. Methods and Results —We conducted a randomized, double-blind, placebo-controlled study of basic fibroblast growth factor (bFGF; 10 or 100 μg versus placebo) delivered via sustained-release heparin-alginate microcapsules implanted in ischemic and viable but ungraftable myocardial territories in patients undergoing CABG. Twenty-four patients were randomized to 10 μg of bFGF (n=8), 100 μg of bFGF (n=8), or placebo (n=8), in addition to undergoing CABG. There were 2 operative deaths and 3 Q-wave myocardial infarctions. There were no treatment-related adverse events, and there was no rise in serum bFGF levels. Clinical follow-up was available for all patients (16.0±6.8 months). Three control patients had recurrent angina, 2 of whom required repeat revascularization. One patient in the 10-μg bFGF group had angina, whereas all patients in the 100-μg bFGF group remained angina-free. Stress nuclear perfusion imaging at baseline and 3 months after CABG showed a trend toward worsening of the defect size in the placebo group (20.7±3.7% to 23.8±5.7%, P =0.06), no significant change in the 10-μg bFGF group, and significant improvement in the 100-μg bFGF group (19.2±5.0% to 9.1±5.9%, P =0.01). Magnetic resonance assessment of the target ischemic zone in a subset of patients showed a trend toward a reduction in the target ischemic area in the 100-μg bFGF group (10.7±3.9% to 3.7±6.3%, P =0.06). Conclusions —This study of bFGF in patients undergoing CABG demonstrates the safety and feasibility of this mode of therapy in patients with viable myocardium that cannot be adequately revascularized.

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Section: Discussionmentioning

confidence: 99%

Local Perivascular Delivery of Basic Fibroblast Growth Factor in Patients Undergoing Coronary Bypass Surgery

et al. 1999

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“…The values of n for membranes prepared by using various amounts of PEO (10,20, and 30 wt.%) while keeping VHCl (15%) and GA (3 ml) constant, ranged from 0.487 to 0.712 leading to a shift of transport from Fickian to the anomalous type. The VHCl-loaded membranes exhibited n values ranging from 0.463 to 0.675 (see Table 2), indicating the shift from erosion type release to a swelling controlled, nonFickian type mechanism.…”

Section: Drug-release Kinetic Parameters Of Different Formulationsmentioning

confidence: 99%

“…Correlation coefficients, r, obtained while fitting the release data are in the range from of 0.934 to 0.997. Figure 6 shows the release profile of VHCl-loaded membranes SP-1, SP-2, and SP-3 at different amounts of drug loading (10,15, and 20 wt.%, respectively) in phosphate buffer solution pH 7.4 (PBS) at 37°C. The release data show that the membrane containing higher amount of VHCl drug (SP-3) displayed faster and higher release rates than those formulations containing lower amount of VHCl.…”

Section: Drug-release Kinetic Parameters Of Different Formulationsmentioning

confidence: 99%

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Sodium alginate/poly (ethylene oxide) blend hydrogel membranes for controlled release of valganciclovir hydrochloride

Mallikarjuna

Rao

Siraj

et al. 2012

Designed Monomers and Polymers

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Sodium alginate (SA) and poly (ethylene oxide) PEO blend membranes were prepared by solvent casting method for the controlled release of valganciclovir hydrochloride, an antiHIV drug. The prepared membranes were thin, flexible, smooth, and characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimeter (DSC), X-ray diffraction (X-RD), scanning electron microscopy (SEM), and tensile strength measurement. FTIR was used to understand the formation of hydrogen bonding between SA and PEO. The DSC and X-RD studies were performed to understand the crystalline nature of drug after encapsulation into the membranes. SEM was used to study the surface morphology of the membranes. Tensile strength measurements revealed the mechanical strength of the membranes. In vitro release studies indicated a dependence of release rate on the extent of crosslinking, amount of drug loading, and the amount of PEO, but slow release rates was extended up to 12 h. Cumulative release data were fitted onto to an empirical equation to compute diffusional exponent (n), which indicated the nonFickian trend for drug release.

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“…Furthermore, previous in vitro studies have identified a stabilizing effect of alginate beads on hydrophilic b-lactam antibiotics and epithelial proliferation growth factors. 8,18,[20][21][22][23][24][25] Thus, alginate is a potential vehicle in a biodegradable carrier system for both antibiotics and bone cells.…”

Section: Introductionmentioning

confidence: 99%

Development of a biodegradable alginate carrier system for antibiotics and bone cells

Ueng

Lee

Lin

et al. 2006

Journal Orthopaedic Research

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This study presents a novel biodegradable alginate delivery system for antibiotics and bone cells to treat infected bone defects. About 2 Â 10 7 New Zealand rabbit mesenchymal stem cells (MSCs) and 5 mL vancomycin solution (50 mg/mL) were added to 5 mL of 2.5% (w/v) sodium alginate solution to form biodegradable antibiotic and MSCs alginate beads 3 mm in diameter. The alginate beads were then cultured in an osteogenic medium for 14 days. The profiles of antibiotics released from the alginate beads were evaluated using the method of high performance liquid chromatography (HPLC). The expression of osteogenic genes, including Cbfa1 and osteopontin, in the alginate beads was determined by reverse transcription-polymerase chain reaction (RT-PCR) analysis. The alkaline phosphatase activity, calcium level, and mineral deposition of the cultured cells within the alginate beads were assessed. Analytical results demonstrated that the concentrations of vancomycin eluted from the alginate beads were, for 14 days, well above the minimal inhibitory concentration of Staphylococcus aureus. Osteopontin and mRNA of Cbfa1 were detected and increased alkaline phosphatase activity and calcium levels were noted, as was a substantial mineral deposition in cultured MSCs. The PKH 26-labeled MSCs and vancomycin alginate beads were implanted in rabbit bony cavities for in vivo analysis. Implanted PKH 26-labeled MSCs were identified in the newly formed bony trabeculae in all specimens at 2 and 4 months after implantation and there was abundant mineral deposition. The results of in vitro study demonstrated sustained elution of vancomycin from the alginate carrier for 14 days and good osteogenic differentiation of cultured MSCs in the alginate carrier matrix. The results of in vivo study demonstrated the implanted MSCs participating in new bone formation. Based on experimental evidence, development of a biodegradable alginate carrier system for antibiotics and bone cells is possible, providing a potential treatment procedure for infected bone defects. ß

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Calcium alginate beads as a slow‐release system for delivering angiogenic molecules In Vivo and In Vitro

Cited by 139 publications

References 35 publications

Local Perivascular Delivery of Basic Fibroblast Growth Factor in Patients Undergoing Coronary Bypass Surgery

Local Perivascular Delivery of Basic Fibroblast Growth Factor in Patients Undergoing Coronary Bypass Surgery

Sodium alginate/poly (ethylene oxide) blend hydrogel membranes for controlled release of valganciclovir hydrochloride

Development of a biodegradable alginate carrier system for antibiotics and bone cells

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