|Articles about Biomaterials|
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| Caprolactonic poloxamer analog: PEG-PCL-PEG
Hwang, M. J., J. M. Suh, et al. (2005), Biomacromolecules 6(2): 885-90.
Abstract: The aqueous solution of poly(ethylene glycol)-poly(caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG) triblock copolymers (> 15. wt. %) undergoing "clear sol-gel-turbid sol" transition as the temperature increases from 20 to 60 degrees C has been developed. Light scattering and 13C NMR study suggested that the transition mechanisms are the micellar aggregation for the clear sol to gel transition (lower transition), whereas the increase in PCL molecular motion for gel to turbid sol transition (upper transition). In contrast to the previous thermogelling biodegradable polymers with a sticky paste morphology, the powder form of the PEG-PCL-PEG triblock copolymers makes it easy to handle and allows fast dissolution in water. Therefore, the lyophilization into a powder form followed by facile reconstitution was possible. This system is believed to be promising for drug delivery, cell therapy, and tissue engineering.
| Carbon nanotubes for biomedical applications
Sinha, N. and J. T. Yeow (2005), IEEE Trans Nanobioscience 4(2): 180-95.
Abstract: Carbon nanotubes (CNTs) have many unique physical, mechanical, and electronic properties. These distinct properties may be exploited such that they can be used for numerous applications ranging from sensors and actuators to composites. As a result, in a very short duration, CNTs appear to have drawn the attention of both the industry and the academia. However, there are certain challenges that need proper attention before the CNT-based devices can be realized on a large scale in the commercial market. In this paper, we report the use of CNTs for biomedical applications. The paper describes the distinct physical, electronic, and mechanical properties of nanotubes. The basics of synthesis and purification of CNTs are also reviewed. The challenges associated with CNTs, which remain to be fully addressed for their maximum utilization for biomedical applications, are discussed.
| Carbonate-containing hydroxyapatite derived from calcium tripolyphosphate gel with urea
Mizutani, Y., M. Hattori, et al. (2005), J Mater Sci Mater Med 16(8): 709-12.
Abstract: Carbonate containing hydroxyapatite (CO3HAp) is one of the candidate materials as a bioresorbable bone substitute. In the present work, CO3HAp was efficiently prepared by a hydrothermal treatment of calcium tripolyphosphate gel with urea at 140 degrees C for 24 h. Chemical potential plots of the CO3HAp for estimation of its dissolution behavior suggested that the CO3HAp is more soluble than hydroxyapatite (HAp) and is as soluble as octacalcium phosphate (OCP) and/or beta -tricalcium phosphate (TCP). This material is expected to be applied to bioresorbable materials such as bone fillers.
| Carboxymethylcellulose-stabilized collagenous rhOP-1 device-a novel carrier biomaterial for the repair of mandibular continuity defects
Wang, H., I. N. Springer, et al. (2004), J Biomed Mater Res A 68(2): 219-26.
Abstract: Human recombinant osteogenic protein-1 (rhOP-1) is osteoinductive. Efforts are made to develop carrier biomaterials with improved space-keeping properties. Bovine collagen type I matrix charged with rhOP-1 was suggested to be an advantageous device of relative liquid quality. We hypothesized that the addition of carboxymethylcellulose (CMC) may stabilize the device and facilitate the regeneration of mandibular continuity defects without further addition of mineralized carrier materials. To test this hypothesis, the anatomical shape, functional remodeling, and mechanical stability of such bony regenerates were evaluated in the course of an animal experiment. Mandibular continuity defects of 5 cm in size were created in five Gottingen minipigs on one side (contralateral hemimandible: control) and bridged with titanium plates. Four animals were treated with the rhOP-1 device (3000 microg rhOP-1, 2 g collagen, 1 g CMC), and one animal was treated with a placebo device omitting rhOP-1. After 12 weeks of experimental period, bony continuity was reestablished in rhOP-1-treated hemimandibles. The bony regenerates were of good anatomical shape, volume, and functional remodeling. Placebo treatment led to insufficient bony regenerates of significant lower bone volume (volume in 3D-CT scan 29.81 cm(3) vs 8.85 cm(3)). To produce 1 mm of bending, 1972 N were needed for rhOP-1-treated hemimandibles, 2617 N for control hemimandibles, and 642 N for the placebo treated hemimandible. CMC stabilization of collagen carrier biomaterials for rhOP-1 provides good plasticity as well as excellent space-keeping properties and may not interfere with osteoinduction. The results of this preliminary study suggest that the applied rhOP-1 device offers a potential option for further studies on the reconstruction of mandibular defects.
| Carboxypeptidases cathepsins X and B display distinct protein profile in human cells and tissues
Kos, J., A. Sekirnik, et al. (2005), Exp Cell Res 306(1): 103-13.
Abstract: Cathepsin X, a recently discovered lysosomal cysteine protease, shares common structural features and activity properties with cysteine protease cathepsin B. Based on its widespread mRNA distribution in primary tumors and tumor cell lines, a redundant function in tumor progression has been proposed. In this study, we have shown that these two related proteases exhibit different profiles with respect to their protein distribution in cells and tissues and to their possible roles in malignancy. Protein level of cathepsin X did not differ significantly between matched pairs of lung tumor and adjacent lung tissue obtained from patients with lung cancer whereas that of cathepsin B was 9.6-fold higher in tumor compared to adjacent lung tissue. Immunohistochemical analysis of lung tumor cathepsin X revealed very faint staining in tumor cells but positive staining in infiltrated histiocytes, alveolar macrophages, bronchial epithelial cells, and alveolar type II cells. Cathepsin X stained positive also in CD68+ cells in germinal centers of secondary follicles in lymph nodes, corresponding to tingible body macrophages. Two cell lines with proven invasive behavior, MCF-10A neoT and MDA-MB 231, showed positive staining for cathepsin B, but negative for cathepsin X. We showed that the invasive potential of MCF-10A neoT cells can be impaired by specific inhibitor of cathepsin B but not by that of cathepsin X. Cathepsin X was found in large amounts in the pro-monocytic U-937 cell line, in monocytes and in dendritic cells, generated from monocytes in vitro. Our results show that cathepsin X is not involved in degradation of extracellular matrix, a proteolytic event leading to tumor cell invasion and metastasis. Its expression, restricted to immune cells suggests a role in phagocytosis and the regulation of immune response.
| Cardiac tissue engineering, ex-vivo: design principles in biomaterials and bioreactors
Shachar, M. and S. Cohen (2003), Heart Fail Rev 8(3): 271-6.
Abstract: Cardiac tissue engineering has emerged as a promising approach to replace or support an infarcted cardiac tissue and thus may hold a great potential to treat and save the lives of patients with heart diseases. By its broad definition, tissue engineering involves the construction of tissue equivalents from donor cells seeded within 3-D biomaterials, then culturing and implanting the cell-seeded scaffolds to induce and direct the growth of new, healthy tissue. In this review, we present an up-to-date summary of the research in cardiac tissue engineering, with an emphasis on the design principles and selection criteria that have been used in two key technologies employed in tissue engineering, (1) biomaterials technology, for the creation of 3-D porous scaffolds which are used to support and guide the tissue formation from dissociated cells, and (2) bioreactor cultivation of the 3-D cell constructs during ex-vivo tissue engineering, which aims to duplicate the normal stresses and flows experienced by the tissues.
| Cardiac valve prostheses: review of clinical status and contemporary biomaterials issues
Schoen, F. J. (1987), J Biomed Mater Res 21(A1 Suppl): 91-117.
| Cardiac valves and valvular pathology: update on function, disease, repair, and replacement
Schoen, F. J. (2005), Cardiovasc Pathol 14(4): 189-94.
Abstract: We summarize herein selected contributions over the past several decades by pathologists and others to the diagnosis, understanding, and management of valvular heart disease, including the structural basis of valve function, the pathology/pathobiology of common naturally occurring and iatrogenic lesions, developments in valve substitution, and novel approaches to valve repair, replacement, and regeneration.
| Cardiovascular applications of biomaterials and implants--an overview
Black, M. M. (1995), J Med Eng Technol 19(5): 151-7.
Abstract: This paper was originally commissioned by the UK Department of Health as a contribution to the work of its Biomaterials and Implants Research Advisory Group. This group was set up under the Chairmanship of Professor Sir Colin Berry with the following terms of reference: (i) to identify recent advances in the field of biomaterials; (ii) to consider the future contribution of biomaterials in improving human health; (iii) to advise the Standing Group on Health Technology in areas where developments and assessment are needed; and (iv) to report to the Director of Research and Development (Professor Sir Michael Peckham) by October 1995. The cardiovascular field was one of several areas in biomaterials/implants considered by the Advisory Group. Amongst other areas considered were orthopaedics, dentistry, urology, wound repair and ophthalmology. Additionally, consideration was also given to such topics as chemical and biochemical sensors, drug release, hydrogels, membranes and artificial organs. The final report of the Advisory Group will be published at the end of this year. However, the Department has agreed that individual working papers such as the present one can be published independently in appropriate scientific journals.
| Cartilage and bone tissue engineering for reconstructive head and neck surgery
Rotter, N., A. Haisch, et al. (2005), Eur Arch Otorhinolaryngol 262(7): 539-45.
Abstract: The loss of cartilage and bone because of congential defects, trauma and after tumor resection is a major clinical problem in head and neck surgery. The most prevalent methods of tissue repair are through autologous grafting or using implants. Tissue engineering applies the principles of engineering and life sciences in order to create bioartificial cartilage and bone. Most strategies for cartilage tissue engineering are based on resorbable biomaterials as temporary scaffolds for chondrocytes or precursor cells. Clinical application of tissue-engineered cartilage for reconstructive head and neck surgery as opposed to orthopedic applications has not been well established. While in orthopedic and trauma surgery engineered constructs or autologous chondrocytes are placed in the immunoprivileged region of joints, the subcutaneous transplant site in the head and neck can lead to strong inflammatory reactions and resorption of the bioartificial cartilage. Encapsulation of the engineered cartilage and modulation of the local immune response are potential strategies to overcome these limitations. In bone tissue engineering the combination of osteoconductive matrices, osteoinductive proteins such as bone morphogenetic proteins and osteogenic progenitor cells from the bone marrow or osteoblasts from bone biopsies offer a variety of tools for bone reconstruction in the craniofacial area. The utility of each technique is site dependent. Osteoconductive approaches are limited in that they merely create a favorable environment for bone formation, but do not play an active role in the recruitment of cells to the defect. Delivery of inductive signals from a scaffold can incite cells to migrate into a defect and control the progression of bone formation. Rapid osteoid matrix production in the defect site is best accomplished by using osteoblasts or progenitor cells.
| Cartilage formation by fetal rat chondrocytes cultured in alginate beads: a proposed model for investigating tissue-biomaterial interactions
Loty, S., J. M. Sautier, et al. (1998), J Biomed Mater Res 42(2): 213-22.
Abstract: Chondrocytes from 21-day-old rat fetal nasal cartilage were cultured in alginate beads for up to 20 days. It was found that chondrocytes retained their spherical shape and typical chondrocytic appearance. During the culture time, chondrocytes underwent differentiation, as demonstrated by the alkaline phosphatase-specific activity and rate of proteoglycan synthesis. Morphological data confirmed chondrocyte differentiation with the appearance of hypertrophic chondrocytes scattered in the alginate gel and a dense extracellular matrix containing filamentous structures and matrix vesicles. In addition, Northern blot analysis performed on day 8 of culture showed that chondrocytes cultured in alginate beads expressed type II collagen mRNA. The alginate bead method also appeared to be suitable for testing biomaterials, and the ready dissolution of the alginate beads by chelating agents provided a simple means for the rapid recovery of encapsulated chondrocytes. Powdered glass-ceramic particles entrapped in the alginate gel were colonized by chondrocytes, which then proliferated and formed a tissue similar to a true calcified cartilaginous structure. These results indicate that the alginate system represents a relevant model for studies of chondrogenesis and endochondral ossification. Furthermore, the encapsulation method could prove useful for studies of tissue-biomaterial interactions in an in vitro environment which more closely mirrors the cartilage matrix than other culture methods.
| Cartilage repair using new polysaccharidic biomaterials: macroscopic, histological and biochemical approaches in a rat model of cartilage defect
Dausse, Y., L. Grossin, et al. (2003), Osteoarthritis Cartilage 11(1): 16-28.
Abstract: OBJECTIVE: The present study aims at evaluating, in a rat model of cartilage defect, the potential of various polymers as filling and repair biomaterials. The macroscopic and histological observations are compared to biochemical parameters in order to appreciate the pertinence of the latter as suitable criteria in tissue engineering. METHODS: A hydrogel, consisting of hyaluronic acid (HA), covalently substituted by hydrophobic alkyl chains (HA12, HA18) and an alginate sponge, alone (Asp) or combined with HA (AHAsp) or combined with HA and chondrocytes (HYBsp) were evaluated. Cartilage lesions were drilled in femoral trochlea of rats. The analyses were performed on trochlea as well as on patella and condyles. RESULTS: Repairs achieved with hydrogels had a similar macroscopic appearance than those afforded by AHAsp and HYBsp. Best macroscopic and histological scores were obtained with HA18 and HYBsp in comparison with alginate group (P< 0.01 and P< 0.02 respectively). Biochemical evaluations confirmed the presence of similar amounts of proteoglycans in the repaired zones and in the controls, though with different DeltadiC4S/DeltadiC6S ratios and enhanced HA levels. CONCLUSIONS: Hydrogels or sponges proved to be colonized by cells synthesizing a matrix with a high HA content. The matrix obtained eventually turns hyaline and takes over the scaffold. The addition of HA and/or chondrocytes to Asp significantly improves the macroscopic and histological scores (P< 0.05 and P< 0.02 respectively). However, biochemical parameters are significantly different of those evaluated in native cartilage. The present study shows that only biochemical parameters allow to discriminate between various biomaterials in tissue engineering and are essential informations which should be taken into account in addition to macroscopic and histological observations.
| Cartilage repair: Generations of autologous chondrocyte transplantation
Marlovits, S., P. Zeller, et al. (2005), Eur J Radiol
Abstract: Articular cartilage in adults has a limited capacity for self-repair after a substantial injury. Surgical therapeutic efforts to treat cartilage defects have focused on delivering new cells capable of chondrogenesis into the lesions. Autologous chondrocyte transplantation (ACT) is an advanced cell-based orthobiologic technology used for the treatment of chondral defects of the knee that has been in clinical use since 1987 and has been performed on 12,000 patients internationally. With ACT, good to excellent clinical results are seen in isolated post-traumatic lesions of the knee joint in the younger patient, with the formation of hyaline or hyaline-like repair tissue. In the classic ACT technique, chondrocytes are isolated from small slices of cartilage harvested arthroscopically from a minor weight-bearing area of the injured knee. The extracellular matrix is removed by enzymatic digestion, and the cells are then expanded in monolayer culture. Once a sufficient number of cells has been obtained, the chondrocytes are implanted into the cartilage defect, using a periosteal patch over the defect as a method of cell containment. The major complications are periosteal hypertrophy, delamination of the transplant, arthrofibrosis and transplant failure. Further improvements in tissue engineering have contributed to the next generation of ACT techniques, where cells are combined with resorbable biomaterials, as in matrix-associated autologous chondrocyte transplantation (MACT). These biomaterials secure the cells in the defect area and enhance their proliferation and differentiation.
| Cartilage repair: surgical techniques and tissue engineering using polysaccharide- and collagen-based biomaterials
Galois, L., A. M. Freyria, et al. (2004), Biorheology 41(3-4): 433-43.
Abstract: Lesions of articular cartilage have a large variety of causes among which traumatic damage, osteoarthritis and osteochondritis dissecans are the most frequent. Replacement of articular defects in joints has assumed greater importance in recent years. This interest results in large part because cartilage defects cannot adequately heal themselves. Many techniques have been suggested over the last 30 years, but none allows the regeneration of the damaged cartilage, i.e. its replacement by a strictly identical tissue. In the first generation of techniques, relief of pain was the main concern, which could be provided by techniques in which cartilage was replaced by fibrocartilage. Disappointing results led investigators to focus on more appropriate bioregenerative approaches using transplantation of autologous cells into the lesion. Unfortunately, none of these approaches has provided a perfect final solution to the problem. The latest generation of techniques, currently in the developmental or preclinical stages, involve biomaterials for the repair of chondral or osteochondral lesions. Many of these scaffolds are designed to be seeded with chondrocytes or progenitor cells. Among natural and synthetic polymers, collagen- and polysaccharide-based biomaterials have been extensively used. For both these supports, studies have shown that chondrocytes maintain their phenotype when cultured in three dimensions. In both types of culture, a glycosaminoglycan-rich deposit is formed on the surface and in the inner region of the cultured cartilage, and type II collagen synthesis is also observed. Dynamic conditions can also improve the composition of such three-dimensional constructs. Many improvements are still required, however, in a number of key aspects that so far have received only scant attention. These aspects include: adhesion/integration of the graft with the adjacent native cartilage, cell-seeding with genetically-modified cell populations, biomaterials that can be implanted without open joint surgery and combined therapies, aimed at disease modification, pain relief and reduction of inflammation.
| Cartilage tissue engineering with novel nonwoven structured biomaterial based on hyaluronic acid benzyl ester
Aigner, J., J. Tegeler, et al. (1998), J Biomed Mater Res 42(2): 172-81.
Abstract: The aim of this study was to investigate the possibility of using the benzyl ester of hyaluronic acid (HYAFF 11), a recently developed semisynthetic resorbable material, as a scaffold for the culture of human nasoseptal chondrocytes in tissue-engineering procedures of cartilage reconstruction. Different techniques such as immunohistochemistry, scanning electron microscopy, and confocal laser scanning microscopy were used to study the behavior, morphology, and phenotype expression of the chondrocytes, which were initially expanded and then seeded on the material. The nonwoven cell carrier allowed good viability and adhesivity of the cells without any surface treatment with additional substances. Furthermore, the cultured cells expressed cartilage-specific collagen type II, indicating that they were able to redifferentiate within the scaffold of HYAFF 11 and were able to retain a chondrocyte phenotype even after a long period of in vitro conditions. Nevertheless, the expression of collagen type I, which was produced by dedifferentiated or incompletely redifferentiated chondrocytes, was noticeable. Additional data were obtained by subcutaneous implantation of samples seeded with human cells in the in vivo model of the athymic nude mouse. The results after 1 month revealed the development of tissue similar to hyaline cartilage. This study is promising for the use of this scaffold for tissue engineering of cartilage replacements.
| Case report: hepatic artery pseudoaneurysm after liver transplantation: definitive treatment with a stent-graft after failed coil embolisation
Maleux, G., J. Pirenne, et al. (2005), Br J Radiol 78(929): 453-6.
Abstract: A 69-year-old woman presented with massive upper gastrointestinal bleeding owing to a ruptured hepatic pseudoaneurysm located at the surgical arterial anastomosis, 2 months after combined liver and kidney transplantation. Initially the pseudoaneurysm was successfully coiled but 3 weeks later recurrence of her symptoms occurred. Hepatic angiography revealed partial reperfusion of the coiled pseudoaneurysm; definitive treatment was performed by placement of an expanded-polytetrafluoroethylene (e-PTFE) covered coronary stent-graft, completely excluding the pseudoaneurysm. Radiological follow-up studies demonstrate a patent stent-graft functioning normally.
| Catalytic three-dimensional protein architectures
Allen, R., R. Nielson, et al. (2005), Anal Chem 77(16): 5089-95.
Abstract: We demonstrate a strategy for microfabricating catalytically active, three-dimensional matrixes composed of cross-linked protein in cellular and microfluidic environments. In this approach, a pulsed femtosecond laser is used to excite photosensitizers via multiphoton absorption within three-dimensionally defined volumes, a process that promotes cross-linking of protein residue side chains in the vicinity of the laser focal point. In this manner, it is possible to fabricate protein microparticles with dimensions on the order of the multiphoton focal volume (less than 1 microm(3)) or, by scanning the position of a laser focal point relative to a specimen, to generate surface-adherent matrixes or cables that extend through solution for hundreds of micrometers. We show that protein matrixes can be functionalized either through direct cross-linking of enzymes, by decoration of avidin matrixes with biotinylated enzymes, or by cross-linking biotinylated proteins that then are linked to biotinylated enzymes via an avidin couple. Several formats are explored, including microparticles that can be translocated to desired sites of action (including cytosolic positions), protein pads that generate product gradients within cell cultures, and on-column nanoreactors for microfluidic systems. These biomaterial fabrication technologies offer opportunities for studying a variety of cell functions, ranging from single-cell biochemistry and development to perturbation and analysis of small populations of cultured cells.
| Catheter-related urinary tract infection
Nicolle, L. E. (2005), Drugs Aging 22(8): 627-39.
Abstract: Indwelling urinary catheters are used frequently in older populations. For either short- or long-term catheters, the infection rate is about 5% per day. Escherichia coli remains the most common infecting organism, but a wide variety of other organisms may be isolated, including yeast species. Bacteria tend to show increased resistance because of the repeated antimicrobial courses. Urinary tract infection (UTI) usually follows formation of biofilm on both the internal and external catheter surface. The biofilm protects organisms from both antimicrobials and the host immune response. Morbidity from UTI with short-term catheter use is limited if appropriate catheter care is practised. In patients with long-term catheters, fever from a urinary source is common with a frequency varying from 1 per 100 to 1 per 1000 catheter days. Long-term care facility residents with chronic indwelling catheters have a much greater risk for bacteraemia and other urinary complications than residents without catheters. Asymptomatic catheter-acquired UTI should not be treated with antimicrobials. Antimicrobial treatment does not decrease symptomatic episodes but will lead to emergence of more resistant organisms. For treatment of symptomatic infection, many antimicrobials are effective. Wherever possible, antimicrobial selection should be delayed until culture results are available. Whether to administer initial treatment by an oral or parenteral route is determined by clinical presentation. If empirical therapy is required, antimicrobial selection is based on variables such as route of administration, anticipated infecting organism and susceptibility, and patient tolerance. Renal function, concomitant medications, local formulary and cost may also be considered in selection of the antimicrobial agent. The duration of therapy is usually 10-14 days, but patients who respond promptly and in whom the catheter must remain in situ may be treated with a shorter 7-day course to reduce antimicrobial pressure. Relevant clinical trials are necessary to define optimal antimicrobial regimens for the management of catheter-acquired UTI. Prevention of catheter-acquired UTI and its complications is a major goal. With short-term catheters, avoiding their use or limiting the duration of use to as short a time as possible are the most effective prevention strategies. Maintaining a closed drainage system and adhering to appropriate catheter care techniques will also limit infection and complications. As the duration of catheterisation is the principal determinant of infection with long-term indwelling catheters, it is not clear that any interventions can decrease the prevalence of bacteriuria in this setting. Catheter flushing or daily perineal care do not prevent infection and may, in fact, increase the risk of infection. Complications of infection may be prevented by giving antibacterials for bacteriuria immediately prior to any invasive urological procedure, and by avoiding catheter blockage, twisting or trauma. The major focus of future advances in prevention of catheter-acquired UTI is the development of biomaterials resistant to biofilm formation. There is substantial current research addressing this issue, but current catheter materials all remain susceptible to biofilm formation.
| Cation effect on thermal transition of iota-carrageenan: a photon transmission study
Pekcan, O. and S. Kara (2005), J Biomater Sci Polym Ed 16(3): 317-33.
Abstract: Coil-to-double helix (c-h) and double helix-to-dimer (h-d) phase transitions of iota-carrageenan in various cation (CaCl2) solutions upon heating and cooling were studied using the photon transmission technique. Photon transmission intensity, Itr, was monitored against temperature to determine the (c-h) and (h-d) transition temperatures (Tch and Thd) and activation energies (DeltaEch and DeltaEhd). An extra dimer-to-dimer (d-d) transition was observed during cooling at low temperature region. However, upon heating dimers directly decompose into double helices by making dimer-to-double helix (d-h) transition. Further heating results in double helix-to-coil (h-c) transition at high temperature region. Tdh and Thc temperatures and Delta Edh and DeltaEhc activation energies were determined. It was observed that Thc and Tch temperatures and DeltaEch and DeltaEhc activation energies were found to be strongly correlated to the CaCl2 content in the system.
| Cationic microparticles consisting of poly(lactide-co-glycolide) and polyethylenimine as carriers systems for parental DNA vaccination
Oster, C. G., N. Kim, et al. (2005), J Control Release 104(2): 359-77.
Abstract: Cationic microparticles for DNA adsorption were formulated by blending poly(lactide-co-glycolide) (PLGA) (50:50), with different cationic agents, either PEI 25 kDa (polyethylenimine) or CTAB (cetyl-trimethyl-ammonium-bromide). The aim was to create adjuvant delivery systems increasing the efficiency of DNA vaccines. Microparticles formulated with 10% PEI exhibited a highly positive zeta-potential, small particle sizes, in contrast to particles prepared with CTAB, which revealed highly aggregated structures in scanning electron micrographs. PEI 10% microparticles efficiently adsorbed DNA and protected DNA from enzymatic degradation. Microparticles with up to 10% PEI did not affect membrane integrity whereas CTAB particles showed higher LDH release. Transfection efficiencies were assessed using a luciferase reporter gene assay compared to naked DNA and PEI/DNA polyplexes. DNA adsorbed onto microspheres with 10% or 50% PEI generally had higher transfection efficiencies than CTAB but reached lower expression levels than PEI/DNA polyplexes alone. This documented the intact release of DNA. The mechanism of gene delivery to non-phagocytic cells was studied via covalent fluorescence labeling of both the DNA and PEI by confocal microscopy and suggested uptake of DNA. Immunization of mice was performed using plasmids encoding immunodominant antigens of Listeria monocytogenes adsorbed onto RG 502 H+PEI 10% microparticles. The efficiency was tested by intravenous challenge with an otherwise lethal dose of L. monocytogenes. PLGA+PEI microspheres can be used as adjuvant delivery systems for DNA but further optimization is necessary to exploit their full potential.
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