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 1,135 records · Page 63Linked to original sources

Fate and effects of the surfactant sodium dodecyl sulfate.

Sodium dodecyl sulfate is the most widely used of the anionic alkyl sulfate surfactants. Its surface-active properties make it important in hundreds of household and industrial cleaners, personal care products, and cosmetics. It is also used in several types of industrial manufacturing processes, as a delivery aid in pharmaceuticals, and in biochemical research involving electrophoresis. SDS synthesis is a relatively simple process involving the sulfation of 1-dodecanol followed by neutralization with a cation source. Purification is accomplished through repeated extraction. It is available commercially in both broad-cut and purified forms. Although its environmental occurrence arises mainly from its presence in complex domestic and industrial effluents, SDS is also directly released in some applications (e.g., oil dispersants and pesticides). Although surfactants are known to significantly contribute to the toxicity of some effluents, no official water quality standards currently exist. Research has shown SDS to be highly biodegradable by a large number of naturally occurring bacteria, and degradation is generally reported to be > or = 90% within 24 hr. The process involves initial enzymatic sulfate liberation and conversion to dodecanoic acid, followed by either beta-oxidative shortening or elongation and desaturation. All surfactant properties are lost after initial sulfate hydrolysis. SDS can enhance absorption of chemicals through skin, gastrointestinal mucosa, and other mucous membranes. Thus, it is used in transepidermal, nasal, and ocular drug delivery systems and to enhance the intestinal absorption of poorly absorbed drugs; enhancement is concentration dependent. Human exposure is mainly through oral ingestion and dermal contact, although cases of respiratory exposure are known. The main sources of daily intake are ingestion of personal care products, residues on insufficiently rinsed utensils, and contaminated drinking water. Uptake, distribution, and excretion of SDS are all rapid. In fish, uptake in various tissues plateaus within 24-72 hr, with elimination occurring within < 24-48 hr; selective accumulation occurs in the hepatopancreas and gall bladder. In mammals, it is readily absorbed via the intestine, colon, and skin. Metabolism is similar in fish and mammals, proceeding from initial omega-oxidation to a carboxylic acid, then to beta-oxidation to butyric acid 4-sulfate, which is finally nonenzymatically desulfurated to gamma-butyrolactone and inorganic sulfate. SDS elicits both physical and biochemical effects on cells, with the membrane the primary target structure. Effects are concentration dependent and range from loss of barrier function and increased permeability to complete cell lysis. Hemolysis in mammals is pH dependent.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Toxicity of intracranial and intraperitoneal O6-benzyl guanine in combination with BCNU delivered locally in a mouse model.

PURPOSE: The DNA-repair protein, O6-alkylguanine-DNA alkyl transferase, may account for resistance of CNS tumors to DNA-alkylating drugs, such as bis-(2-chloroethyl)-1-nitrosourea (BCNU). The therapeutic effects of BCNU can be potentiated by inhibiting the repair protein with an alkylated guanine analog, O6-benzyl guanine (O6BG). To investigate potential toxicity of this inhibition, we examined the effects of O6BG in mice treated with intracranial (i.c.) BCNU given via a biodegradable polymer. METHODS: Mice were treated with escalating doses of BCNU chronically delivered i.c., and with chronically delivered O6BG. The O6BG was delivered via a 7-day intraperitoneal (i.p.) or i.c. osmotic minipump. Toxicity of the combination therapies was measured from survival data. Bone marrow response was estimated from white blood cell counts. RESULTS: Combining systemic (i.p.) O6BG with locally (i.c.) delivered BCNU resulted in a decrease in the maximum tolerated dose (MTD) of local BCNU. With local delivery of O6BG, the MTD of BCNU in combination with O6BG was increased. CONCLUSIONS: Based on the results of this study, a dose escalation study will be necessary when combining systemic O6BG with the higher doses of i.c. BCNU.

Animals↗

AC electrospray biomaterials synthesis.

A rapid, viable and safe fabrication method for biomaterials synthesis is reported using high-frequency AC electrospraying. We demonstrate its potential for polymeric nanoparticle fabrication, drug encapsulation in mono-dispersed micron-sized biodegradable polymer shells and the synthesis of 1microm biodegradable fibers with adjustable pore sizes as bioscaffolds for tissue/orthopaedic engineering and wound care therapy. The absence of charge in the ejected drops and fibers facilitates pulmonary drug delivery, polymer encapsulation and minimizes protein/DNA denaturing or compound ionization.

Biocompatible Materials↗

Transmucosal macromolecular drug delivery.

Mucosal surfaces are the most common and convenient routes for delivering drugs to the body. However, macromolecular drugs such as peptides and proteins are unable to overcome the mucosal barriers and/or are degraded before reaching the blood stream. Among the approaches explored so far in order to optimize the transport of these macromolecules across mucosal barriers, the use of nanoparticulate carriers represents a challenging but promising strategy. The present paper aims to compare the characteristics and potential of nanostructures based on the mucoadhesive polysaccharide chitosan (CS). These are CS nanoparticles, CS-coated oil nanodroplets (nanocapsules) and CS-coated lipid nanoparticles. The characteristics and behavior of CS nanoparticles and CS-coated lipid nanoparticles already reported [A. Vila, A. Sanchez, M. Tobio, P. Calvo, M.J. Alonso, Design of biodegradable particles for protein delivery, J. Control. Rel. 78 (2002) 15-24; R. Fernandez-Urrusuno, P. Calvo, C. Remunan-Lopez, J.L. Vila-Jato, M.J. Alonso, Enhancement of nasal absorption of insulin using chitosan nanoparticles, Pharm. Res. 16 (1999) 1576-1581; M. Garcia-Fuentes, D. Torres, M.J. Alonso, New surface-modified lipid nanoparticles as delivery vehicles for salmon calcitonin (submitted for publication).] are compared with those of CS nanocapsules originally reported here. The three types of systems have a size in the nanometer range and a positive zeta potential that was attributed to the presence of CS on their surface. They showed an important capacity for the association of peptides such as insulin, salmon calcitonin and proteins, such as tetanus toxoid. Their mechanism of interaction with epithelia was investigated using the Caco-2 model cell line. The results showed that CS-coated systems caused a concentration-dependent reduction in the transepithelial resistance of the cell monolayer. Moreover, within the range of concentrations investigated, these systems were internalized in the monolayer in a concentration-dependent manner. This uptake was slightly enhanced by the presence of the CS coating but, as compared with previously published results [M. Garcia-Fuentes, C. Prego, D. Torres, M.J. Alonso, Triglyceride-chitosan nanostructures for oral calcitonin delivery: evaluation in the Caco-2 cell model and in vivo (submitted for publication)], highly dependent on the nature of the lipid core. Nevertheless, these differences in the uptake of the CS-coated systems (solid lipid core or oily core) by the Caco-2 cells did not have a consequence in the in vivo behaviour. Indeed, both CS-coated systems (nanocapsules and CS-coated nanoparticles) showed an important capacity to enhance the intestinal absorption of the model peptide, salmon calcitonin, as shown by the important and long-lasting decrease in the calcemia levels observed in rats.

Administration, Intranasal↗

Ectopic induction of cartilage and bone by bovine bone morphogenetic protein using a biodegradable polymeric reservoir.

Two kinds of bone morphogenetic protein (BMP) containing polymeric reservoirs made from poly(lactide-co-glycolide) (PLG) and a mixture of PLG/poly(ethylene glycol) (PEG) (PLG/PEG) were implanted into mice femoral muscles. In the PLG/PEG reservoir with BMP, bone formation was induced within 3 weeks. On the other hand, in the PLG reservoir with BMP scarcely any bone formation could be observed. The results suggest that the carrier system is most important for the development of BMP-induced bone formation and the PLG/PEG reservoir system is available for BMP delivery.

Animals↗

Lectins and microparticles for enhanced oral vaccination.

Oral administration is an attractive means of vaccination since it alleviates the need for injection and trained personnel. Furthermore, effective oral vaccination induces immune responses locally in the gastrointestinal tract, the site of colonisation and infection by many pathogens. However, since most proteins and peptides are degraded in the gut, do not interact specifically with the epithelium, or induce strong immune responses, this route of delivery is generally inefficient. Two of the most promising potential approaches are the use of lectins to target vaccines to the epithelium and the association of vaccines with biodegradable microparticles. This paper describes methods to assess the stability of vaccines and targeting molecules in the gastrointestinal tract, interaction with the mucosa, uptake into internal organs and induction of mucosal antibody responses.

Administration, Oral↗

Local delivery of doxorubicin for malignant glioma by a biodegradable PLGA polymer sheet.

Implantable, biocompatible and biodegradable devices bearing an anticancer drug can provide promising local therapy to patients with malignant disorders. With the aim of treating brain tumors, especially gliomas, a membranous sheet containing doxorubicin was produced by co-polymerization to poly(D,L-lactide-co-glycolide) (PLGA). When release of the drug from the sheet was measured, sustained release continued until day 34. The data contrasted with the burst release from material containing a higher proportion of the drug. In terms of biodegradability, a subcutaneous 3 x 3-mm tetragonal sheet was almost completely absorbed by day 80. When a glioma was implanted subcutaneously and the tumor nodule exposed to the sheet, the device inhibited tumor growth significantly. The sheet consisted of an amorphous structure with cavities estimated to have a diameter of 0.5 - 3 microm by electron microscopic observation. Since the sheet is implantable, biodegradable and has a sustained-drug release property, the device may play a role in the local therapy of brain tumors.

Animals↗

Designing polymer conjugates as lysosomotropic nanomedicines.

Marriage of cell biology (the concept of 'lysosomotropic drug delivery') and the realization that water-soluble synthetic polymers might provide an ideal platform for targeted drug delivery led to the first synthetic polymer-drug conjugates that entered clinical trials as anticancer agents. Conceptually, polymer conjugates share many features with other macromolecular drugs, but they have the added advantage of the versatility of synthetic chemistry that allows tailoring of molecular mass and addition of biomimetic features. Conjugate characteristics must be optimized carefully to ensure that the polymeric carrier is biocompatible and that the polymer molecular mass enables tumour-selective targeting followed by endocytic internalization. The polymer-drug linker must be stable in transit, but be degraded at an optimal rate intracellularly to liberate active drug. Our early studies designed two HPMA [N-(2-hydroxypropyl)methacrylamide] copolymer conjugates containing doxorubicin that became the first synthetic polymer-drug conjugates to be tested in phase I/II clinical trials. Since, a further four HPMA copolymer-anticancer drug conjugates (most recently polymer platinates) and the first polymer-based gamma-camera imaging agents followed. Polymer-drug linkers cleaved by lysosomal thiol-dependent proteases and the reduced pH of endosomes and lysosomes have been used widely to facilitate drug liberation. It is becoming clear that inappropriate trafficking and/or malfunction of enzymatic activation can lead to new mechanisms of clinical resistance. Recent studies have described HPMA copolymer conjugates carrying a combination of both endocrine and chemotherapy that are markedly more active than individual conjugates carrying a single drug. Moreover, current research is investigating novel dendritic polymer architectures and novel biodegradable polymers as drug carriers that will provide improved drug delivery and imaging probes in the future. The present paper reviews the clinical status of polymeric anticancer agents, the rationale for the design of polymer therapeutics and discusses the benefits and challenges of lysosomotropic delivery.

Antineoplastic Agents↗

Poly(lactide-co-glycolide) microspheres for the controlled release of oligonucleotide/polyethylenimine complexes.

In this article, microspheres able to induce the controlled release of oligonucleotide/polyethylenimine complexes are proposed. A model oligonucleotide (the oligothymidilate pdT16) was encapsulated within poly(lactide-co-glycolide) microspheres alone or associated with polyethylenimine (PEI) at different nitrogen/phospate (N/P) ratios. Microspheres were prepared by the multiple emulsion-solvent evaporation technique and characterized for morphology, diameter, encapsulation efficiency, and release kinetics. The introduction of PEI in the internal aqueous phase resulted in the formation of a soluble complex with pdT16 and in a strong increase of the oligonucleotide encapsulation efficiency. PEI affected microsphere morphology inducing the formation of very porous particles yielding to an accelerated release of pdT16. When incubated with HeLa cells, microspheres encapsulating pdT16/PEI complexes allowed both a reduction of the complex toxicity and an improvement of the intracellular penetration of the released oligonucleotide. We conclude that biodegradable microspheres encapsulating oligonucleotides/PEI complexes have a great potential as controlled release system because they allow the sustained release of an oligonucleotide carrier that crosses biological membranes and locates in nucleus.

Biocompatible Materials↗

Vancomycin encapsulation in biodegradable poly(epsilon-caprolactone) microparticles for bone implantation. Influence of the formulation process on size, drug loading, in vitro release and cytocompatibility.

Vancomycin encapsulation in biodegradable poly(epsilon-caprolactone) microparticles (200 microm mean diameter) was most efficient with a simple emulsion technique that dispersed 122.5 mg/g of polymer. Scanning electron micrographs showed smooth or pitted particles. Dissolution studies were correlated with microparticle morphology, indicating higher release with pitted particles when vancomycin was encapsulated in a dissolved state. The cytocompatibility of these poly(epsilon-caprolactone) microparticles was demonstrated by a direct contact cytotoxic assay. This material can be considered as an efficient drug delivery system for bone implantation.

Absorbable Implants↗

Induction of mucosal immune responses following enteric immunization with antigen delivered in alginate microspheres.

Oral immunization is the most effective way of inducing immune responses in the intestinal tract. Biodegradable microspheres have been used extensively for the delivery of antigens to the Peyer's patches (PPs) within the gut-associated lymphoid tissue (GALT). We evaluated various formulations of alginate microspheres for their capacity to induce mucosal immune responses in vivo. Multiple intestinal "loops" each containing a single PP, were surgically prepared in lambs. We have previously showed that PP in individual intestinal loops function as independent sites for the induction of immune responses. This animal model provides a system for directly comparing different antigen formulations within the same animal. Individual intestinal loops were injected with a model antigen, porcine serum albumin (PSA) encapsulated in three different formulations of alginate micropsheres. Three weeks after immunization, PSA-specific immune responses were assayed with antibody secreting cell (ASC) ELISPOT, lymphocyte proliferative responses (LPRs), IFN-gamma production and antibody secreted into intestinal loops. PSA encapsulated in alginate micropsheres or in saline induced humoral immune responses as indicated by the presence of numerous ASC. However, PSA-specific T-cell responses (LPR and IFN-gamma production) were not induced.

Alginates↗

Biodegradable implantable fluconazole delivery rods designed for the treatment of fungal osteomyelitis: influence of gamma sterilization.

Fluconazole poly(D,L-lactic) acid (PLA) and poly(L-lactic) acid (L-PLA) implantable delivery rods were studied, in vitro and in vivo, as an alternative treatment of fungal osteomyelitis. Implantable rods loaded with 5% fluconazole (FLU) were prepared by the injection-molding method and sterilized by gamma-irradiation at a dose of 25 kGy. Loading efficiency, physical chemistry (high performance liquid chromatography, X-ray diffraction, gel permeation chromatography), and in vitro and in vivo release assays were performed to evaluate the novel delivery systems and the sterilization effect on implant characteristics. In spite of polymer degradation after gamma-irradiation, the loading efficiency, chemical stability, and crystallographic structure of FLU were not affected. In vivo studies were carried out in femoral bone marrow of rabbits. Approximately 85 and 80% of the total dose were released within 12 and 4 weeks from PLA and L-PLA rods, respectively. This showed a faster release rate of FLU in vivo than in vitro, showing almost zero-order kinetics from PLA rods.

Animals↗

An NLS peptide covalently linked to linear DNA does not enhance transfection efficiency of cationic polymer based gene delivery systems.

BACKGROUND: Transfection with non-viral gene delivery vectors, such as cationic polymers, generally results in low transgene expression in vivo. This is likely due to poor cytoplasmic transport and intra-nuclear DNA delivery. METHODS: In this study two strategies to improve nuclear import were investigated. Linear DNA constructs with or without an NLS peptide were prepared by PCR. Alternatively, linear DNA obtained by enzymatic cleavage followed by capping of both ends with DNA-hairpins was used. An NLS peptide was attached to one of the capped ends of the linear DNA. Both biodegradable (pDMAEAppz) and non-degradable polymers (PEI or pDMAEMA) were used to complex the DNA. Several cell types, dividing and non-dividing, were transfected with the linear DNA constructs containing a SV40-derived NLS peptide. Nuclear import of the DNA constructs was studied using digitonin-permeabilized cells. RESULTS: Linear DNA prepared by PCR proved not useful as it was degraded from the 3'end. Linear DNA capped with hairpins was more successful with regard to stability. However, Cells transfected with linear DNA constructs by electroporation or by using cationic polymers with linear DNA containing a NLS peptide, failed to show significantly higher luciferase expression levels when compared to cells transfected with plasmid DNA or linear DNA without an NLS peptide attached. No nuclear localization was observed in digitonin-permeabilized cells. CONCLUSION: Taken together, these data demonstrate that this nuclear localisation signal when attached to DNA is neither able to improve transfection efficiency of cationic polymers nor the nuclear import of the DNA constructs.

Active Transport, Cell Nucleus↗

Long-term histopathological study of new polypeptidic biomaterials.

The long-term histopathological evaluation of a new class of synthetic polypeptides, the poly(tert-butyloxycarbonylmethyl glutamates), as implantable drug delivery systems is addressed. This evaluation was performed in rat muscles over one year. The histological analysis included the measurement of many parameters, such as the type and thickness of the collagen capsule. The influence of the presence of progesterone, the selected active drug, could also be monitored over time.

Animals↗

[The research on IR and TEM of polybutylcyanoacrylate nanoparticles].

Through latex polymerization with stabilizer (Dextran, low fraction), we prepared polybutylcyanoacrylate nanoparticles with a size of approximately 200 nm. The nanoparticle diameter decreases with decreasing stabilizer concentration. Using TEM and IR we studied the combination state and the mechanism between polybutylcyanoacrylate and Dextran. It was shown that each Dextran molecule could therefore contain several cyanoacrylate polymer moieties covalently linked via any of the available Dextran hydroxyl groups. Anchoring of the cyanoacrylate groups within the nanoparticle matrix would therefore result in an irreversible attachment between the Dextran and the nanoparticle. In this way, Dextran could be incorporated throughout the particle matrix as well as on the surface, producing the biodegradable particle. The results have been interpreted by reference to the accepted theories of steric stabilization and dispersion polymerization, and a model is proposed for the nanoparticle formation in the presence of Dextran.

Biocompatible Materials↗

VEGF scaffolds enhance angiogenesis and bone regeneration in irradiated osseous defects.

UNLABELLED: Bone regeneration is challenging in sites where the blood supply has been compromised by radiation. We examined the potential of a growth factor (VEGF) delivery system to enhance angiogenesis and bone formation in irradiated calvarial defects. VEGF-releasing polymers significantly increased blood vessel density and vascular perfusion in irradiated defects and increased bone formation relative to control conditions. INTRODUCTION: Radiation therapy causes damage to tissues and inhibits its regenerative capacity. Tissue injury from radiation is in large part caused by a compromised vascular supply and reduced perfusion of tissues. The aim of this study was to determine if delivery of vascular endothelial growth factor (VEGF) from a biodegradable PLGA (copolymer of D,L-lactide and glycolide) scaffold could enhance neovascularization and bone regeneration in irradiated osseous defects. MATERIALS AND METHODS: An isolated area of the calvarium of Fisher rats was irradiated (12 Gy) 2 weeks preoperatively, and two 3.5-mm osseous defects were created in this area, followed by the placement of PLGA scaffolds or VEGF scaffolds (PLGA scaffolds with incorporated VEGF) into the defects. Laser Doppler perfusion imaging was performed to measure perfusion of these areas at 1, 2, and 6 weeks. Implants were retrieved at 2, 6, and 12 weeks, and histologic and muCT analyses were performed to determine neovascularization and bone regeneration. RESULTS: Histological analyses revealed statistically significant increases in blood vessel formation (>2-fold) and function (30%) within the VEGF scaffolds compared with PLGA scaffolds. Additionally, evaluation of bone regeneration through bone histomorphometric and muCT analyses revealed significantly greater bone coverage (26.36 +/- 6.91% versus 7.05 +/- 2.09% [SD]) and increased BMD (130.80 +/- 58.05 versus 71.28 +/- 42.94 mg/cm(3)) in VEGF scaffolds compared with PLGA scaffolds. CONCLUSIONS: Our findings show that VEGF scaffolds have the ability to enhance neovascularization and bone regeneration in irradiated osseous defects, outlining a novel approach for engineering tissues in hypovascular environments.

Animals↗

Gene Therapy for Restenosis: Progress or Frustration?

No systemic pharmacological treatment has been shown to convincingly reduce the incidence of restenosis after angioplasty in patients. The lack of success of many pharmaceutical agents in reducing restenosis rates post-angioplasty and following stent-implementation shown in dozens of clinical trials has encouraged the development of new technological approaches as treatment. Gene therapy has the potential to prevent some of the sequelae after arterial injury, particularly cell proliferation. Mechanical methods of preventing restenosis, such as sophisticated local drug delivery strategies and biodegradable stents using new materials in combination with gene therapy, may be of use to maximize safety and efficiency.

Journal Article↗