Colonic drug delivery: enhanced release of indomethacin from cross-linked chondroitin matrix in rat cecal content.
Explore the source record for details and available documents.
Animals↗
SEARCH · Search PubMed
Results for “Biodegradable Delivery Systems”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Injectable microcapsules prepared with biodegradable poly(alpha-hydroxy) acids for prolonged release of drugs.
In this paper, microencapsulation techniques for the preparation of drug-containing monolithic microcapsules for prolonged release using biodegradable poly(alpha-hydroxy) acids, such as polylactic acid, poly(lactide-co-glycolide) and copoly(lactic/glycolic) acid are reviewed. Phase separation, solvent evaporation, and spray drying procedures are discussed. In order to achieve controlled-release formulations of highly water-soluble drugs that are entrapped efficiently, various manufacturing techniques and procedures have been developed. Degradation of poly(alpha-hydroxy) acids is altered by the copolymer ratio and molecular weight of the polymer used to make microcapsules and the amounts of released microencapsulated drugs correlate almost linearly with polymer degradation, indicating that controlled-release formulations, which release drugs over different times, can be prepared using suitable poly(alpha-hydroxy) acids with different degradation rates.
Biocompatible Materials↗
Experimental study of coil embolization using a new atelocollagen spring coil.
Spring steel coils have been used to occlude abnormal vessels in patients with a congenital heart malformation. However, long-term adverse effects of steel spring coils remain uncertain, although some long-term results appear to be good. The purpose of this study was to evaluate the angiographic and histologic results of coil embolization experimentally using a biodegradable atelocollagen coil that we have recently developed. The spring coil was made from a 30% atelocollagen solution mixed with a contrast medium. The delivery system consisted of a 5-F end-hole catheter and a 3-F modified biotome catheter as a catch and release system. Coil embolization was percutaneously attempted in 12 dogs, and only one coil was placed in each dog so that a variety of endothelial coverage could be evaluated both in complete and incomplete occlusion. At 1 wk to 5 mo after the procedure, the occluded vessels were resected and examined histologically. Postprocedural angiography showed complete occlusion in 6 of the 12 vessels and partial occlusion in 6. Follow-up angiography showed complete occlusion in 8 and incomplete occlusion in 4. Histologic examination revealed that diffuse thrombosis around the coil loops and the exchange between blood and contrast medium were detectable as early as 7 d after embolization. Atelocollagen was gradually replaced with fibrous tissue and became markedly degraded by 5 mo. Atelocollagen spring coils can be used to occlude abnormal vessel effectively and safely. The histologic reactions and the fate of the coil seem to be within tolerable limits. This experimental study supports the feasibility of a clinical trial of this coil embolization in patients with an aorticopulmonary collateral artery.
Animals↗
Targeted and sustained delivery of aclarubicin to lymphatics by lactic acid-oligomer microsphere in rat.
We examined targeted delivery of an anticancer drug, aclarubicin (ACR), to the lymphatic system in rats by encapsulation of the drug in microsphere (MS) prepared from nontoxic and biodegradable L-lactic acid-oligomer with an average molecular weight (Mw) of 3600. ACR was released at an almost constant rate from two kinds of ACR-MSs having different size (1-5 microns and less than 1 micron) over 20 d in phosphate-buffered saline at 37 degrees C. The intraperitoneal administration of both ACR-MSs (dose of ACR; 5 mg/kg) to rats sustained an almost constant ACR level (300-400 and 400-600 ng/ml) in the lymph of the thoracic duct during over 10 d, and the ACR level in the blood was extremely low, although intraperitoneal injection of ACR alone gave lower level of ACR in the lymph than in the blood level within 12 h.
Aclarubicin↗
Biodegradable polymer releasing antibiotic developed for drainage catheter of cerebrospinal fluid: in vitro results.
The authors developed a biodegradable polymer that releases an antibiotic (nalidixic acid) slowly and continuously, for prevention of catheter-induced infection during drainage of cerebrospinal fluid. We investigated the in vitro antibiotic releasing characteristics and bacterial killing effects of the new polymer against E. coli. The novel fluoroquinolone polymer was prepared using diisopropylcarbodiimide, poly (e-capro-lactone) diol, and nalidixic acid. FT-IR, mass spectrometry, and elemental analysis proved that the novel antibacterial polymer was prepared successfully without any side products. Negative MS showed that the released drug has a similar molecular weight (M.W.=232, 350) to pure drug (M.W.=232). In high pressure liquid chromatography, the released drug and drug-oligomer showed similar retention times (about 4.5-5 min) in comparison to pure drug (4.5 min). The released nalidixic acid and nalidixic acid derivatives have antibacterial characteristics against E. Coli, Staphylococcus aureus, and Salmonella typhi, of more than 3 months duration. This study suggests the possibility of applying this new polymer to manufacture drainage catheters that resist catheter-induced infection, by delivering antibiotics for a longer period of more than 1 month.
Anti-Bacterial Agents↗
Development of a new biodegradable intravascular polymer stent with simultaneous incorporation of bioactive substances.
OBJECTIVE: Due to the thrombogenicity and permanent implant nature of metallic stents, bioresorable synthetic polymers have been proposed for stents and local drug delivery systems. Bioresorbable polyesters like poly(D,L-lactide) demonstrated excellent biocompatibility in various tissues. This paper describes a novel method for the molding of these polymers. The specific CESP-process (Controlled Expansion of Saturated Polymers) is characterised by the use of the plasticizer carbon dioxide and allows the incorporation of bioactive substances at physiologic temperatures into the polymer bulk and the production of complex designed implants. METHODS: The CESP-process is characterised by the exposure of an amorphous polymer to an inert gas at high pressure with a significant lower glass transition point. The plasticizing effect makes it possible to process polylactides at a temperature close to room temperature. The low process temperature constitutes a key advantage for thermally sensitive polymers and allows the incorporation of thermally sensitive pharmaceutical additives. To obtain some preliminary information on the biocompatibility, in vitro cell toxicity testing as well as drug release assessment was performed. RESULTS: Different polymer sheets were produced using the CESP-process. Cytotoxicity was not observed in any molded polymer material. According to the mechanical and biocompatibility results Poly(D,L-lactide) (P-DL-LA) was investigated in the CESP-process. Finite element analysis was used to test the possible geometry of an adequate stent. A helical design was chosen and a stent-prototype was produced using the CESP-process. Peroxidase activity as an incorporated marker enzyme could be measured over 6 weeks. Different drug release profiles were obtained due to various pore sizes of the polymer. CONCLUSIONS: The new CESP-process can be used to process biodegradable polymers and to mold different stent geometries without inducing cytotoxic effects to the material. Furthermore, this procedure permits the simultaneous incorporation of bioactive substances during the molding process. Drug release kinetics can be regulated by different pore sizes of the material.
Absorbable Implants↗
Fabrication, implantation, elution, and retrieval of a steroid-loaded polycaprolactone subretinal implant.
A subretinal drug delivery system was developed to overcome the limitations of current treatments for retinal disease. A rod-shaped implant was made by embedding the corticosteroid triamcinolone acetonide within a biodegradable polycaprolactone polymer matrix. The implant was fabricated by homogeneously mixing the polymer and drug in solvent. The mixture was then dried, melted, and extruded, and the prepared solid form was drawn into a filament. The rods were mechanically sectioned to a length of 2 mm with a diameter of up to 320 microm. The rods were successfully implanted into the subretinal space of six rabbits. No complications were observed during the 4-week follow-up period. Initial observations of the implantation and elution characteristics revealed that polycaprolactone is well tolerated by the retinal tissue and that the implant can elute steroid for a period of at least 4 weeks without eliciting inflammatory response or complications. In vitro drug elution rates of different polymer to drug ratios and geometries into a balanced salt solution/bovine serum albumin (1%) solution showed an early rapid-release phase and late first-order phase. Histology and device retrieval after implantation revealed minimal encapsulation and good preservation of cellular morphology during the follow-up period and a more fibrous polymer microstructure of the implant.
Absorbable Implants↗
Recent advances in the use of microspheres for targeted therapy.
In recent years the concept of using small colloidal particles for the selective delivery of drugs has been explored experimentally using a variety of different physical systems (for example, phospholipid vesicles (liposomes), triglyceride emulsions, albumin microspheres) and routes of administration. In such studies the aim has been to target a potent pharmacological agent on an organ or tissue site, thereby reducing adverse reactions and side-effects, or to provide a means of controlled release. The design of appropriate delivery systems must take into account the nature of the target and physiological barriers to targeting as well as factors such as drug loading and drug release, stability of the carrier system and its biocompatibility and biodegradation. Targeting with microspheres can be divided into passive methods that rely upon physiological and physicochemical determinants such as entrapment in capillary beds (lungs - particle size) or uptake by phagocytic cells (liver-surface characteristics), an active method whereby the particle is directed to a specific site through the use of surface coatings (surfactants, glycolipids, monoclonal antibodies) or a material sensitive to an external influence. Candidate systems presently under study are described. These include lipid emulsions for intravenous administration and microspheres for intra-articular delivery.
Adrenal Cortex Hormones↗
Polymer controlled drug delivery system for growth hormone.
The use of biomaterials as vehicles for pharmacological agents, hormones, and growth factors is at times the best treatment for controlled local administration. Our study was designed to evaluate the in vitro biocompatibility and potential clinical use of a new polymer, hydroxyethyl methacrylate-vinyl pirrolidone. Human fibroblasts were incubated in the presence of the polymer and/or growth hormone, and evaluation was made of both the rate of polymer and hormone degradation and the proliferative effect on the fibroblast population. Results indicate that this polymer is biodegradable and lacks toxicity toward these cells. The hormone was slowly released, as suggested by enhanced cell proliferation.
Drug Delivery Systems↗
Peripheral nerve regeneration with sustained release of poly(phosphoester) microencapsulated nerve growth factor within nerve guide conduits.
Prolonged delivery of neurotrophic proteins to the target tissue is valuable in the treatment of various disorders of the nervous system. We have tested in this study whether sustained release of nerve growth factor (NGF) within nerve guide conduits (NGCs), a device used to repair injured nerves, would augment peripheral nerve regeneration. NGF-containing polymeric microspheres fabricated from a biodegradable poly(phosphoester) (PPE) polymer were loaded into silicone or PPE conduits to provide for prolonged, site-specific delivery of NGF. The conduits were used to bridge a 10 mm gap in a rat sciatic nerve model. Three months after implantation, morphological analysis revealed higher values of fiber diameter, fiber population and fiber density and lower G-ratio at the distal end of regenerated nerve cables collected from NGF microsphere-loaded silicone conduits, as compared with those from control conduits loaded with either saline alone, BSA microspheres, or NGF protein without microencapsulation. Beneficial effects on fiber diameter, G-ratio and fiber density were also observed in the permeable PPE NGCs. Thus, the results confirm a long-term promoting effect of exogenous NGF on morphological regeneration of peripheral nerves. The tissue-engineering approach reported in this study of incorporation of a microsphere protein release system into NGCs holds potential for improved functional recovery in patients whose injured nerves are reconstructed by entubulation.
Absorbable Implants↗
Modified polyethylenimines as non viral gene delivery systems for aerosol therapy: effects of nebulization on cellular uptake and transfection efficiency.
This study examined the effect of nebulization on the cellular uptake and transfection efficiency of polyplexes from four polyethylenimine (PEI) modifications: branched 25 kDa PEI (bPEI), linear 22 kDa PEI (linPEI), pegylated PEI (pegPEI) and biodegradable PEI (bioPEI). Polyplexes were aerosolized with air-jet and ultrasonic nebulizers. The aerosol was collected and used to determine complex size and zeta potential. Fluorescence-assisted cell sorting (FACS) was used to quantify the cellular association of polyplexes in primary alveolar cells (AEC), A549 cells and primary bronchial cells (BEC). Confocal laser scanning microscopic images provided information about the internalization of polyplexes. Transfection efficiencies of polyplexes were quantified via measurement of luciferase expression. All polymers were stable during nebulization, although size increases were observed after air-jet nebulization. FACS studies showed a two- to three-fold increase in polyplex association with BEC compared to A549 cells, while polyplex association with AEC was negligible. BPEI, linPEI and bioPEI polyplexes were internalized, while pegPEI polyplexes remained predominately attached to the cellular membrane. Luciferase expression was detected only in BEC and A549 cells with transfection efficiencies approximately one order of magnitude higher in BEC. All PEI modifications investigated were suitable for aerosol therapy, although cell type and polymer structure significantly influenced the uptake and transfection efficiency of the polyplexes.
Aerosols↗
Effect of GDNF-releasing biodegradable microspheres on the function and the survival of intrastriatal fetal ventral mesencephalic cell grafts.
The transplantation of fetal ventral mesencephalic (FVM) cell suspensions into the brain striatal system is an alternative approach for the treatment of Parkinson's disease (PD). However, one objection to this procedure is the relatively poor survival of implanted cells. Attempts have been made to improve the survival of grafted dopaminergic neurons using glial cell line-derived neurotrophic factor (GDNF). Nevertheless, the clinical application of GDNF is limited, due to the difficulties in administering a protein to the brain tissue and due to the ubiquity of its receptor, thus leading to neurological side effects. A strategy to deliver GDNF in the brain based on the intracerebral implantation of biodegradable poly(D,L-lactic acid-co-glycolic acid) sustained release microspheres has been developed. Such microparticles can be easily implanted by sterotaxy in precise and functional areas of the brain without causing damage to the surrounding tissue. Moreover, the release profile of the GDNF-loaded microspheres showed a sustained release over 56 days of biologically active GDNF at clinically relevant doses. The present study shows that the implantation of GDNF-loaded microspheres at a distance to the site of FVM cells in the 6-hydroxydopamine-lesioned rat model of PD improves dopaminergic graft survival and function. Furthermore, the unloaded and the GDNF-loaded microspheres, when they are mixed with FVM cells, may provide a mechanical support and a 3D environment inducing differentiation and increased function of dopaminergic neurons. Taken together, these results show that GDNF microspheres represent an efficient delivery system for cell transplantation studies.
Animals↗
Modified polyethylenimines as non-viral gene delivery systems for aerosol gene therapy: investigations of the complex structure and stability during air-jet and ultrasonic nebulization.
Polyelectrolyte complexes between DNA and polyethylenimine (PEI) are promising non-viral delivery systems for pulmonary inhalation gene therapy and thus require sufficient stability during nebulization. The structure and stability of four different PEI-DNA polyplexes, namely branched (bPEI), linear (linPEI), poly(ethylene glycol)-grafted PEI (PEGPEI), biodegradable (bioPEI) PEI with DNA, were investigated. Using atomic force microscopy, the morphology of DNA and polyplexes before and after both air-jet and ultrasonic nebulization was characterized. The influence of nebulization on physico-chemical properties, particle size and zeta potential, was studied. Efficient DNA condensation to spherical particles was achieved with bPEI (90 nm) and PEGPEI (110 nm). By contrast, incomplete DNA condensations, seen as flower structures, were observed with linPEI (110 nm) and bioPEI (105 nm). Air-jet nebulization altered the polyplex structure to a greater extent than ultrasonic nebulization and resulted mainly in smaller and non-spherical particles (30-200 nm). Ultrasonic nebulization did not change the spherical structure or particle size of the polyplexes. In particular, the shape and size of the PEGPEI polyplexes did not change. We conclude that ultrasonic nebulization is a milder aerosolization method for gene delivery systems based on PEI. Additionally, PEGPEI-DNA polyplexes seem to be more stable than their counterparts, which may be advantageous in pulmonary inhalation gene therapy.
Aerosols↗
Positively charged gelatin microspheres as gastric mucoadhesive drug delivery system for eradication of H. pylori.
Gastric mucoadhesive drug delivery systems are very promising for eradication of Helicobacter pylori (H. pylori), a spiral bacterium that resides in the gastric mucus layer and at the mucus-epithelial cell interface. New positively charged biodegradable microspheres were prepared using aminated gelatin by surfactant-free emulsification in olive oil, followed by a cross-linking reaction with glutaraldehyde. The amino group contents of the modified gelatin and the microspheres were determined using a 2,4,6-trinitrobenzenesulfonic acid method. With the increase of glutaraldehyde concentration, the amino group content of the microspheres decreased accordingly. The influence of glutaraldehyde concentration, cross-linking reaction time, drug-loading patterns, and type of release media on the in vitro release characteristics of amoxicillin from the microspheres was investigated. Amoxicillin release rate from the modified gelatin microspheres was significantly reduced compared with that from gelatin microspheres. Furthermore, the release was decreased with the increase of glutaraldehyde concentration and/or cross-linking time. On the other hand, a faster release was observed in a lower pH release medium and/or using a lower pH solution for amoxicillin loading. The gastric mucoadhesive properties of the microspheres were evaluated using RITC-labeled microspheres in an isolated rat stomach. The gastric mucoadhesion of the modified gelatin microspheres was markedly improved compared with that of gelatin microspheres. The modified gelatin microsphere proves to be a possible candidate delivery system for the effective eradication of H. pylori.
Adhesives↗
Local drug delivery: current applications.
Catheter-based treatment of coronary artery disease has historically been based on expansion or ablating vessels. Only in the last 3 years have we had devices that allow us to choose the location to apply agents directly onto or into the arterial wall. Previous trials of pharmaceutical agents in humans have failed despite animal trials showing efficacy. These agents were given in high systemic doses of drugs that may have toxic side effects with minimal effect at the site of arterial injury. Percutaneous interventions are still limited by our need to treat thrombus, alter or passivate the arterial wall, and deliver new treatments into or through the arterial wall. This review discusses the current designs of delivery catheters, ongoing trials of locally delivered agents and gene therapy. The limits of our current understanding of delivery location and efficiency as well as future investigations are also discussed.
Animals↗
Environment-sensitive hydrogels for drug delivery.
Environmentally sensitive hydrogels have enormous potential in various applications. Some environmental variables, such as low pH and elevated temperatures, are found in the body. For this reason, either pH-sensitive and/or temperature-sensitive hydrogels can be used for site-specific controlled drug delivery. Hydrogels that are responsive to specific molecules, such as glucose or antigens, can be used as biosensors as well as drug delivery systems. Light-sensitive, pressure-responsive and electro-sensitive hydrogels also have the potential to be used in drug delivery and bioseparation. While the concepts of these environment-sensitive hydrogels are sound, the practical applications require significant improvements in the hydrogel properties. The most significant weakness of all these external stimuli-sensitive hydrogels is that their response time is too slow. Thus, fast-acting hydrogels are necessary, and the easiest way of achieving that goal is to make thinner and smaller hydrogels. This usually makes the hydrogel systems too fragile and they do not have mechanical strength necessary in many applications. Environmentally sensitive hydrogels for drug delivery applications also require biocompatibility. Synthesis of new polymers and crosslinkers with more biocompatibility and better biodegradability would be essential for successful applications. Development of environmentally sensitive hydrogels with such properties is a formidable challenge. If the achievements of the past can be extrapolated into the future, however, it is highly likely that responsive hydrogels with a wide array of desirable properties can be made.
Animals↗
Composite biomaterials based on ceramic polymers. I. Reinforced systems based on Al2O3/PMMA/PLLA.
Composite biomaterials with good mechanical response and a partially biodegradable character were prepared by the free radical polymerization of mixtures of alpha-Al2O3, low-molecular-weight but crystalline poly(L-lactic acid) (PLLA), and methyl methacrylate (MMA). Cylindrical specimens prepared with different composition were characterized by thermogravimetry, calorimetry, 1H-NMR spectroscopy, and x-ray diffraction (XRD). The in vitro biodegradative process was studied in different media, following variations of the pH, gravimetric weight loss of the specimens, and crystalline domain change by XRD after immersion in pure water and buffered solutions at pH 4.0 and pH 8.0 for 90 days. Formation of a relatively porous structure with good cohesion after the biodegradative treatment (confirmed by SEM) was observed. These systems can be considered for applications in orthopedic surgery as filling biomaterials and even as control drug-delivery systems.
Aluminum Oxide↗
A pH- and ionic strength-responsive polypeptide hydrogel: synthesis, characterization, and preliminary protein release studies.
A novel polypeptide hydrogel has been synthesized by crosslinking poly(L-glutamic acid) (PLG) with poly(ethylene glycol) (PEG). The PLG-PEG hydrogel was shown to be highly hydrophilic, and the extent of swelling varied with pH, increasing at higher ionization of the PLG. Aside from electrostatic effects, such as ion-ion repulsion and internal ion osmotic pressure, circular dichroism studies showed that swelling response to pH also is affected by secondary structural attributes associated with the polypeptide backbone. Modification of the polypeptide by changing its hydrophobicity and degree of ionization was an effective method for altering the overall extent of pH-responsive swelling. Rapid de-swelling (contraction) was observed when the PLG-PEG hydrogel was transferred from high to low pH buffer solution, and this swelling/de-swelling behavior was reversible over repeated cycles. Drug release from swollen hydrogels was examined using the model protein lysozyme. Rapid de-swelling of the hydrogel was found to be an effective means of facilitating lysozyme release. The crosslinking of synthetic polypeptides with PEG appears to be a highly versatile approach to the preparation of pH-responsive biodegradable hydrogels.
Biocompatible Materials↗