Search PubMed⌕ Search

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.

At least 721 records · Page 40Linked to original sources
PubMed1984

Controlled-release delivery systems for hormones. A review of their properties and current therapeutic use.

Biomedical engineering approaches used to develop controlled-release delivery systems for hormones are here reviewed regarding system design and therapeutic applications. The biomedical engineering approach uses a system of non-drug components to control the rate and duration of hormone delivery. The non-drug components vary from system to system, but generally include: a reservoir for the hormone; a barrier or regulator to contain the hormone within the reservoir and to control its release; an energy source to remove the hormone from the reservoir; and a pathway for egress of the hormone from the system. Controlled-release delivery systems for hormones discussed in this review include mechanical and osmotic pumps; intraocular, intravaginal and intrauterine platform devices; biodegradable and non-biodegradable subcutaneous implants; and small particulate systems including microcapsules, microspheres and liposomes. Examples of the therapeutic application of the various systems are given along with a discussion of design factors and pharmacological aspects relevant to their clinical use.

Amenorrhea↗
PubMed2002

Regenerative biology and medicine.

The replacement of damaged tissues and organs with tissue and organ transplants or bionic implants has serious drawbacks. There is now emerging a new approach to tissue and organ replacement, regenerative biology and medicine. Regenerative biology seeks to understand the cellular and molecular differences between regenerating and non-regenerating tissues. Regenerative medicine seeks to apply this understanding to restore tissue structure and function in damaged, non-regenerating tissues. Regeneration is accomplished by three mechanisms, each of which uses or produces a different kind of regeneration-competent cell. Compensatory hyperplasia is regeneration by the proliferation of cells which maintain all or most of their differentiated functions (e.g., liver). The urodele amphibians regenerate a variety of tissues by the dedifferentiation of mature cells to produce progenitor cells capable of division. Many tissues contain reserve stem or progenitor cells that are activated by injury to restore the tissue while simultaneously renewing themselves. All regeneration-competent cells have two features in common. First, they are not terminally differentiated and can re-enter the cell cycle in response to signals in the injury environment. Second, their activation is invariably accompanied by the dissolution of the extracellular matrix (ECM) surrounding the cells, suggesting that the ECM is an important regulator of their state of differentiation. Regenerative medicine uses three approaches. First is the transplantation of cells into the damaged area. Second is the construction of bioartificial tissues by seeding cells into a biodegradable scaffold where they produce a normal matrix. Third is the use of a biomaterial scaffold or drug delivery system to stimulate regeneration in vivo from regeneration-competent cells. There is substantial evidence that non-regenerating mammalian tissues harbor regeneration-competent cells that are forced into a pathway of scar tissue formation. Regeneration can be induced if the factors leading to scar formation are inhibited and the appropriate signaling environment is supplied. An overview of regenerative mechanisms, approaches of regenerative medicine, research directions, and research issues will be given.

Journal Article↗
PubMed1994

Transforming growth factor-alpha-Pseudomonas exotoxin fusion protein (TGF-alpha-PE38) treatment of subcutaneous and intracranial human glioma and medulloblastoma xenografts in athymic mice.

Epidermal growth factor receptor (EGFR) is amplified or overexpressed in many malignant gliomas and other primary brain tumors but is low or undetectable in normal brain. In the present study, this differential expression has been exploited for targeted brain tumor therapy using a TGF-alpha-Pseudomonas exotoxin recombinant toxin, TGF-alpha-PE38. In vitro experiments demonstrate that the cytotoxicity of this fusion protein is primarily determined by tumor EGFR expression and that TGF-alpha-PE38 cytotoxicity is abolished by pretreatment with excess epidermal growth factor. Treatment with i.p. TGF-alpha-PE38 in nude mice bearing glioblastoma or medulloblastoma s.c. xenografts produced tumor regression and growth delay. For intracranial xenograft implants treated with i.p. TGF-alpha-PE38, significant increases in median survival were noted only for tumors with the highest EGFR expression. However, intracranial tumors treated with a single intratumoral injection of TGF-alpha-PE38 showed increased survival in all xenografts tested. These results indicate that TGF-alpha-PE38 is active against primary human brain tumors ranging from moderate to high EGFR expression. For intracranial tumors, however, the higher survival rates produced by intracranial injection of TGF-alpha-PE38 than by continuous i.p. administration suggest that increased drug clearance or impaired drug delivery reduces the efficacy of systemic TGF-alpha-PE38. Direct delivery of TGF-alpha-PE38 into brain tumors by controlled-release biodegradable polymers or intratumoral implanted catheters, or intrathecal administration into the colony stimulating factor of patients with leptomeningeal metastasis, may represent clinically useful applications of recombinant toxin therapy in tumors with high EGFR expression.

Animals↗
PubMed1997

Ganciclovir-loaded polymer microspheres in rabbit eyes inoculated with human cytomegalovirus.

PURPOSE: To test the antiviral effect of ganciclovir released from biodegradable polymer microspheres in rabbit eyes inoculated with human cytomegalovirus (HCMV). METHODS: Human cytomegalovirus (5 x 10(3) plaque forming unit in 0.1 ml Hank's balanced salt solution) was inoculated 4 days after gas compression vitrectomy. Injected after 2 days was 10 mg of 300- to 500-micron ganciclovir-loaded microspheres (89.77 micrograms ganciclovir/mg) suspended in 0.1 ml of 2% hydroxypropylmethylcellulose. Blank microspheres were injected as control specimens. Vitritis, retinitis, and optic neuritis were graded from 0(+)-4+ for 14 days to separate the early HCMV-induced disease events from later nonspecific host inflammatory responses. Ganciclovir-loaded microspheres also were injected and observed for biodegradation and tissue reaction for 8 weeks. RESULTS: In eyes injected with ganciclovir-loaded microspheres, vitritis decreased from days 3 to 14, and retinitis and optic neuritis decreased from days 3 to 9. In eyes injected with blank microspheres, vitritis increased from days 3 to 7, retinitis increased from days 3 to 9, and optic neuritis increased from days 3 to 14. Immunofluorescence of HCMV antigens in retinal tissues was shown only in eyes injected with blank microspheres. Histopathologic analysis showed minimal focal disruption of the retinal architecture in eyes injected with ganciclovir-loaded microspheres. Disorganization of the normal retinal architecture was observed in eyes injected with blank microspheres. No adverse tissue reaction was observed clinically and histopathologically in eyes injected with ganciclovir-loaded microspheres after 8 weeks. CONCLUSIONS: Ten milligrams of 300 to 500 microns ganciclovir-loaded poly(D,L-lactide-co-glycolide) microspheres control the progression of fundus disease in HCMV-inoculated rabbit eyes.

Animals↗
PubMed2002

Production and characterization of biodegradable Povidone-iodine microsphere as a intramammary disinfectant.

Microspheres composed of biocompatible, biodegradable poly DL-lactide-co-glycolide (DL-PLGA) and Povidone-iodine were evaluated as an intramammary disinfectant delivery system in vitro prior to infusion into mammary glands. Microsphere was prepared by solvent evaporation method and particle size, morphology and in vitro release kinetics were examined. The microspheres were ranged in size from 25 microm to 155 microm (mean diameter = 65.7 microm). Povidone-iodine was dispersed on the surface of microsphere and microsphere was spherical in shape with a smooth surface. The yield of microsphere was 57.3% and the encapsulation efficiency was 69.6%. In in vitro release study, a burst effect (50.9%) was observed during the first two days and a sustained release then continued for the next 28 days. Results of the present study demonstrated that microsphere have the potential for new intramammary disinfectant formulations that can provide increased efficacy of therapy against mastitis pathogens.

Animals↗
PubMed2006

Local vascular toxicokinetics of stent-based drug delivery.

One of the major limitations of balloon angioplasty is early restenosis as a result of elastic recoil leading to vessel occlusion. The constrictive (negative) remodeling of the blood vessel is overcome by implanting a balloon expandible metal stent to dilate the artery and thereby prevent elastic recoil. However, bare metal stent implants cause mechanical injury to the intima and release of inflammatory mediators which then initiates formation of neointimal layer leading to restenosis. In-stent restenosis is histologically distinct from restenosis following balloon angioplasty, in which in-stent restenosis is accompanied by increased smooth muscle proliferation, migration, extracellular matrix and collagen synthesis leading to neointimal hyperplasia. To overcome neointimal hyperplasia, stents have been coated with pharmacological agents that inhibit smooth muscle cell proliferation and migration. The drug and polymer combination coated onto stent device is an efficient form of drug delivery system which can provide high concentrations of drug in the tissues over an extended period of time to achieve antiproliferative therapeutic effect. The permanent stent implants pose the risk of a continuous interaction between the non-biodegradable polymer coating and intimal surface leading to physical irritation, endothelial dysfunction, hypersensitivity reactions, delayed healing and excess risk of late stent thrombosis. This review highlights the relationship between local drug delivery using the stent platform, release kinetics and local vascular toxicity.

Angiogenesis Inhibitors↗
PubMed2004

Drug delivery systems: past, present, and future.

Drug delivery systems are essential components of drugs controlled release. In the last decades, several drug delivery technologies have emerged including capsules, liposomes, microparticles, nanoparticles, and polymers. These components must be biocompatible, biodegradable, and display a desired biodistribution providing a long-term availability of the therapeutic at specific target over time.

Biocompatible Materials↗
PubMed2002

Controlled release of NFkappaB decoy oligonucleotides from biodegradable polymer microparticles.

The objective of this study was to evaluate a poly(DL-lactic-co-glycolic acid)/poly(ethylene glycol) (PLGA/PEG) delivery system for nuclear factor-kappa B (NFkappaB) decoy phosphorothioated oligonucleotides (ODNs). PLGA/PEG microparticles loaded with ODNs were fabricated with entrapment efficiencies up to 70%. The effects of PEG contents (0, 5, and l0 wt%), ODN loading densities (0.4, 4, and 40 microg/mg), and pH of the incubation medium (pH 5, 7.4. and 10) on ODN release kinetics from the PLGA/PEG microparticles were investigated in vitro for up to 28 days. The release profiles in pH 7.4 phosphate buffered saline (PBS) were characterized by an initial burst during the first 2 days, a linear release phase until day 18, and a final release phase for the rest of the period. Up to 85% of the ODNs were released after 28 days in pH 7.4 PBS regardless of the ODN loading density and PEG content. Higher ODN loading densities resulted in lower entrapment efficiencies and greater initial burst effects. The bulk degradation of PLGA was not significantly affected by the PEG content and ODN loading density, but significantly accelerated at acidic buffer pH. Under acidic and basic conditions, the aggregation of microparticles resulted in significantly lower cumulative mass of released ODNs than that released at neutral pH. The effects of pH were reduced by the incorporation of PEG into PLGA microparticles. Since the PLGA degradation products are acidic, PLGA/PEG microparticles might provide a better ODN delivery vehicle than PLGA microparticles. These results suggest that PLGA/PEG microparticles are useful as delivery vehicles for controlled release of ODNs and merit further investigation in cell culture and animal models of glioblastoma.

Biocompatible Materials↗
PubMed2006

Polymers as biomaterials for tissue engineering and controlled drug delivery.

The advent of biodegradable polymers has significantly influenced the development and rapid growth of various technologies in modern medicine. Biodegradable polymers are mainly used where the transient existence of materials is required and they find applications as sutures, scaffolds for tissue regeneration, tissue adhesives, hemostats, and transient barriers for tissue adhesion, as well as drug delivery systems. Each of these applications demands materials with unique physical, chemical, biological, and biomechanical properties to provide efficient therapy. Consequently, a wide range of degradable polymers, both natural and synthetic, have been investigated for these applications. Furthermore, recent advances in molecular and cellular biology, coupled with the development of novel biotechnological drugs, necessitate the modification of existing polymers or synthesis of novel polymers for specific applications. This review highlights various biodegradable polymeric materials currently investigated for use in two key medical applications: drug delivery and tissue engineering.

Biocompatible Materials↗
PubMed2004

Endodontic-periodontal locally delivered antibiotics.

Endodontic pathology is a bacterial disease. It is well established that periapical disease is the result of bacteria, their product, and the host response to them. Periradicular disease will occur after microorganisms and their metabolic products affect the periradicular tissue. Aim of using antibiotics as part of a treatment regimen is to achieve, within the periodontal environment, a concentration of the drug that is sufficient either to kill (bactericidal) or arrest the growth (bacteriostatic) of pathogenic microorganisms. There are two possible approaches to improve the drug action: sustained and controlled drug release to reduce or eliminate side effects by improving the therapeutic index and site-specific drug delivery to minimize systemic effects. These two strategies have been explored by the association of drugs with different vehicles, either naturals or synthetics. A wide variety of specialized local delivery systems (i.e.intrapocket devices) have been designed to maintain the antibiotic in the GCF (gingival crevicular fluid) at a concentration higher than the MIC (minimum inhibitory concentration). Fibres, films, strips and microparticles made of biodegradable or non-biodegradable polymers have been reported as effective methods to administer antibacterial agents for periodontal therapy. Together with these solid devices, semisolid adhesive or non-adhesive formulations have also been proposed.

Anti-Bacterial Agents↗
PubMed2005

One-step preparation of polyelectrolyte-coated PLGA microparticles and their functionalization with model ligands.

This work aimed at the development of a novel surfactant-free, one-step process for the concomitant formation of poly(lactide-co-glycolide) (PLGA) microparticles (MP) and surface coating with the polyelectrolyte chitosan, which is suitable for subsequent covalent conjugation of bioactive ligands. The technology is based on solvent extraction from an O/W-dispersion using a static micromixer. Surface coating occurred through interaction of the negatively charged, nascent PLGA MP with the polycationic chitosan, which was dissolved in the aqueous extraction fluid. Particles of 1-10 mum in diameter were produced with excellent reproducibility. The chitosan-coated PLGA MP were spherical and showed a smooth surface without pores, as demonstrated by scanning electron microscopy (SEM). The chitosan coatings were characterized by zeta potential measurements and X-ray photoelectron spectroscopy (XPS). The functional amino groups of chitosan were used to conjugate two model ligands to the coating, i.e. fluorescamine and NHS-PEG-biotin. The presence of the conjugated ligands was revealed by confocal laser scanning microscopy (CLSM) and fluorescence activated cell sorting (FACS). Evidence for biotinylation was demonstrated through binding of fluorescently labelled streptavidin. The developed platform technology is straightforward and flexible. Future studies will focus on the design of microparticulate carriers with bioactive surfaces, e.g. as antigen delivery systems.

Biocompatible Materials↗
PubMed2005

Studies on functionalization of poly(epsilon-caprolactone) by a cholesteryl moiety.

Biodegradable polymers/oligomers based on epsilon-caprolactone (CL) were end-functionalized by a cholesteryl moiety. The functionalized polymers/oligomers, Chol-(CL)n, were synthesized through ring-opening polymerization initiated by cholesterol with a hydroxyl group. The chemical structure of end-functionalized polymers/oligomers was confirmed by FT-IR and 1H-NMR. The molecular weight of the functionalized polymer/oligomer increases with decreasing feed ratio of the initiator cholesterol to the monomer CL. Incorporation of the cholesteryl moiety to the polymer chain results in liquid crystallinity for the resultant oligomers when their molecular chains are not very long. The enzymatic degradation of the functionalized polymers/oligomers was investigated. The microsphere drug-delivery system of a functionalized oligomer was fabricated and its drug release properties were evaluated. The cell-culture experiment indicates the incorporation of cholesteryl moiety to the polymer chain results in improved cell proliferation.

3T3 Cells↗
PubMed2001

Azo-containing urethane analogues for colonic drug delivery: synthesis, characterization and in-vitro evaluation.

A urethane-based analogue containing an azo aromatic linkage in the backbone was synthesized for use in colon-specific delivery systems by reacting toluene-2,6-diisocyanate with a mixture of an aromatic azo diol, (bis-4-hydroxyphenyl)-4,4'-diazobiphenyl, poly(ethylene glycol) (Mn = 4000; number-average molecular weight) and 1,2-propanediol (propylene glycol). The resultant compounds (UR-1 and UR-2) were characterized by IR spectroscopy, 1H NMR spectroscopy, DSC studies, X-ray diffraction studies and molecular weight determination by gel permeation chromatography. The compounds exhibited low molecular weight, lacked film-forming properties and crystallinity in the structure. An in-vitro bacterial degradation test to demonstrate the susceptibility of azo bond to bacterial enzymes was performed using media inoculated with lactobacillus culture. The results indicated degradation of films by azoreductase. In-vitro permeation of 5-aminosalicylic acid was studied in control and lactobacilli-treated films. The permeability of the lactobacilli treated films was significantly increased suggesting the potential of these compounds for application in colonic targeting.

Antineoplastic Agents↗
PubMed2002

Polyphosphoester microspheres for sustained release of biologically active nerve growth factor.

Controlled delivery of neurotrophic proteins to a target tissue by biodegradable polymer microspheres has been explored widely for its potential applications in the treatment of various disorders in the nervous system. We investigated in this study the potential of polyphosphoester microspheres as carriers for the sustained release of nerve growth factor (NGF), a water-soluble neurotrophic protein. Two polyphosphoesters (PPEs), P(BHET-EOP/TC) and P(DAPG-EOP), as well as poly(lactide/glycolic acid) (PLGA), were used to fabricate microspheres by a W/O/W emulsion and solvent evaporation/extraction method. With bovine serum albumin as a model protein to optimize processing parameters. P(DAPG-EOP) microspheres exhibited a lower burst effect but similar protein entrapment levels and efficiencies when compared with those made of PLGA. Bioactive NGF could be released for at least 10 weeks from the P(DAPG-EOP) microspheres, as confirmed by a neurite outgrowth assay of the PC12 cells. These NGF containing microspheres were incorporated into the nerve guide conduits that were implanted to bridge a 10 mm gap in a rat sciatic nerve model. Two weeks after implantation, immunostaining with an antibody against the neurofilament protein confirmed the presence of axons at the distal end of regenerated cables within the NGF microsphere-loaded conduits. These results demonstrated the feasibility of using biodegradable PPEs for microencapsulation of NGF and provided a basis for future therapeutic application of the microspheres.

Animals↗
PubMed2004

Microwave-treated gelatin microspheres as drug delivery system.

The crosslinking process of natural macromolecules with microwave energy should have the potentiality to overcome the problems due to the toxicity of the residuals of chemical crosslinking agents and moreover of the "in vivo" biodegradation products of the chemical crosslinked macromolecule. To evaluate the effective crosslinking of the gelatin forming the microspheres, the water-soluble fraction at 37 degrees C, the water absorption capability, the free amino and free carboxylic acid groups of the gelatin were determined. The structural change in the gelatin microspheres has been detected by the porosity studies. Moreover, both the "in vitro" biodegradability and the biocompatibility of the gelatin microspheres microwave-treated after a subcutaneous injection into female albino guinea pigs were tested. As the results suggest only the gelatin microspheres microwave-treated for 10 min at an inlet temperature of 250 degrees C could have been modified by the crosslink formation among the macromolecular chains. The gelatin microspheres treated with the microwave energy were very well biodegraded as indicated both by the "in vitro" enzymatic degradation studies and mainly by the histopathological examination. This latter study has also demonstrated the biocompatibility of the gelatin microspheres crosslinked with the microwave energy. In order to evaluate the feasibility of the microwave crosslinking process for pharmaceutical applications, both the drug loading and the drug release processes were evaluated using diclofenac as drug model, either as acidic form or as sodium salt. The microspheres were swollen in aqueous solution of diclofenac sodium salt, followed by a washing procedure with cool water to maintain the sodium salt into the microspheres or with pH 1.5 HCl to induce the diclofenac precipitation. To increase the amount of diclofenac acid form in the microspheres, the procedure was repeated three times washing with pH 1.5 HCl after each swelling process. Both the X-ray diffractometry and thermal analysis investigations showed a different physical state of the two drug forms in the microspheres, i.e. the amorphous state of the sodium salt and the crystalline state of the acidic form. According to the experimental results, the drug is released from gelatin microspheres according to the drug loading and the drug solubility.

Animals↗
PubMed2006

Site-specific delivery of dexamethasone from biodegradable implants reduces formation of pericardial adhesions in rabbits.

Repeated sternotomy often leads to serious complications in patients due to the formation of cardiac adhesions. In this study we characterized dexamethasone-loaded biodegradable poly(lactide)-poly(ethyleneglycol) copolymer films for site-specific drug delivery and examined their efficacy in the rabbit model of postoperative cardiac adhesions. Tritiated dexamethasone-loaded films were used to determine the in vitro release and in vivo drug distribution. Dexamethasone release in serum was biphasic with 69% drug released after 72 hr. The implants produced sustained drug levels at the implantation site with low distribution into the peripheral tissues. The matrices were implanted in rabbits between the epicardium and the sternum following sternotomy, pericardiectomy and epicardium abrasion, with the drug-releasing surface facing the epicardium. The tenacity and density of the adhesions was examined 21 days post procedure in comparison to both groups of untreated and rabbits implanted with blank matrices. Similarly tenacious and dense adhesions were observed in both control groups. In contrast, epicardial adhesions' formation was significantly reduced and the anatomy was preserved in the treated animals. It is concluded that local delivery of dexamethasone from biodegradable implants provides a promising approach for the prevention of pericardial adhesions while potentially minimizing the systemic adverse effects inherent to systemic therapy or high blood levels of the drug.

Animals↗
PubMed1994

Transmitter-loaded polymeric microspheres induce regrowth of dopaminergic nerve terminals in striata of rats with 6-OH-DA induced parkinsonism.

Biodegradable controlled-release microspheres made with the biocompatible biodegradable polyester excipient poly (DL-lactide-co-glycolide) represent a new technology for drug delivery to the central nervous system (CNS). A suspension of 3 microliters of dopamine (DA) or NE containing microspheres, or empty microspheres, was implanted in 2 sites of the DA denervated striatum of rats previously unilaterally lesioned with 6-OH-DA. Contralateral rotational behavior induced by apomorphine was used as an index of lesion success. Following implantation of the microspheres, rotational behavior was also used as an index of functional recovery. Both DA and NE microsphere implanted rats displayed a 30-50% reduction in the number of apomorphine induced rotations up to 12 weeks post implantation. Empty microspheres caused no changes in rotational behavior. Implantation of a mixture of DA/NE microspheres resulted in an 80% decrease in the number of apomorphine induced rotations, registered up to 4 weeks. Immunocytochemical examination revealed growth of DA and tyrosine hydroxylase immunoreactive fibers in the striatum of DA and NE microsphere implanted rats. Interestingly, functional behavior correlated with the degree of fiber ingrowth. This method to deliver substances to the CNS will be tested for therapeutic usefulness in patients with Parkinson's disease, in a recently approved clinical trial in Göteborg.

Animals↗
PubMed2002

Poly(L-lysine)-g-poly(D,L-lactic-co-glycolic acid) micelles for low cytotoxic biodegradable gene delivery carriers.

Poly(lactic-co-glycolic acid) (PLGA)-grafted poly(L-lysine) (PLL) (PLL-g-PLGA) was synthesized to demonstrate its micelle-forming property in an aqueous solution. The micelles were used as a gene delivery carrier. The hydrodynamic diameter of PLL-g-PLGA micelles in an aqueous solution was ca. 149 nm with a narrow size distribution. Critical micelle concentration (cmc) was 9.6 mg/l. The PLL-g-PLGA micelles could be used to produce compact nanoparticulate complexes with plasmid DNA, which could efficiently protect the complexed DNA from enzymatic degradation by DNase I. The micelle/DNA complexes had highly compacted structure sized between 200-300 nm with a positive surface charge value. The PLL-g-PLGA micelles exhibited much higher transfection efficiency with lower cytotoxicity than PLL. Here, we demonstrated that biodegradable and cationic PLL-g-PLGA micelles could be used as an effective DNA condensation carrier for gene delivery system.

3T3 Cells↗