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Results for “Biodegradable Delivery Systems”

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At least 19 recordsLinked to original sources

PubMed1996

2 multi-center trials assessing the clinical efficacy of 5% sanguinarine in a biodegradable drug delivery system.

A biodegradable drug delivery system containing 5% sanguinarium (Sa) was compared to vehicle control (VC), scaling and root planing (SRP), and supragingival plaque control (SPC) in the treatment of adult periodontitis in 2 well-controlled clinical trials. Studies were 4-quadrant (split mouth) designs at 2 centers each, having 94 (Study A) and 107 (Study B) patients. All patients had at least 3 pockets between 5 and 9 mm that bled on probing, in each quadrant. Probing pocket depth (PD), clinical attachment level (AL), bleeding on probing (BOP), and plaque index were recorded at baseline, 14, 30, 60, and 90 days. All treatments gave statistically significant reductions from baseline for PD and BOP, and significant gains for AL. For PD reduction, SRP was superior to all test groups at all time points in both studies (p < 0.001). Sa was superior to VC in Study A at 14 and 30 days and to SPC at all time points. For AL gain at 90 days, in both studies, SRP gave gains of 0.42 and 0.78 mm respectively with superiority seen over the SPC group at 90 days (p < 0.001) in study A only, For BOP reduction, in Study A SRP was superior to Sa, VC, and SPC at 60 and 90 days (p < 0.005) and in Study B superiority to Sa and VC was at 90 days and to SPC at 60 days (p < 0.05). Sa was superior to VC for pocket depth in deep pockets only. Sa failed to demonstrate superiority over VC on a consistent basis. Analysis of residual Sa indicates that Sa potency was insufficient to show an advantage beyond clinical effects inherent in treatments with VC and SPC.

Adult↗

PubMed1995

Biodegradable delivery system for a birth control vaccine: immunogenicity studies in rats and monkeys.

PURPOSE: The purpose of this study was to develop a single administration delivery system for a model birth control vaccine, in order to reduce the need for multiple injections and enhance immunogenicity. METHODS: The immunogen-loaded microspheres were prepared by solvent evaporation method and characterized for loading levels, size distribution and in vitro release kinetics. The microspheres were immunized intramuscularly in wistar rats and bonnet monkeys, and the antibody response was compared to that obtained with the same total dose of the immunogen on alum given at a monthly interval. RESULTS: Results indicated that a single injection of the immunogen entrapped in the microspheres generated a response comparable to that obtained by the same immunogen on alum injected at a monthly interval. The antibodies generated by the microspheres in the monkeys also had a good bioneutralization capacity indicating immunogen integrity during the microencapsulation process. CONCLUSIONS: Biodegradable microspheres served as an effective delivery system for a model immunogen used in this study to reduce the need for frequent immunizations and enhance immunogenicity.

Animals↗

PubMed1981

Use of synthetic polypeptides in the preparation of biodegradable delivery systems for narcotic antagonists.

The goal of this program was the development of biocompatible sustained-release systems that would release naltrexone at a rate of 20 to 25 microgram/hr for 30 days, and that would biodegrade within 90 days. The focus was on the use of macrocapsules prepared from synthetic polypeptides, specifically copolymers of glutamic acid and ethyl glutamate (i.e., Glu/EGlu copolymers). Tubular capsules prepared from 18/82 Glu/EGlu were the most promising systems developed. Capsules 1 cm in length, 0.19 cm in outside diameter, and 0.005 cm in wall thickness released naltrexone in mice at rates in the range of 20 to 40 microgram/hr for 18 days. The rates then decreased during the next 12 days as the capsules became exhausted of drug. These capsules were biocompatible and they appeared to biodegrade within 90 days. In general, the Glu/EGlu copolymers exhibit permeation and degradation rates that increase as the glutamic acid content is increased. Radiotracing studies revealed that the ultimate degradation product was carbon dioxide, which appeared in the expired air. This result is consistent with a polypeptide degradation process that involves hydrolysis of the ethyl esters followed by hydrolysis of the peptide bonds to produce glutamic acid, which enters the metabolic pool.

Animals↗

PubMedDate not supplied

Formulation factors for preparing ocular biodegradable delivery system of 5-fluorouracil microparticles.

Microparticles containing 5-fluorouracil (5-FU) were prepared using poly(DL-lactide-co-glycolide) with an oil-in-oil emulsion/solvent extraction technique. Particle characteristics including size distribution, 5-FU loading efficiencies, in vitro release and degradation were investigated. The dispersed phase was composed of PLG dissolved in dichloromethane, and the continuous phase was paraffin oil containing lecithin. 5-FU was successfully entrapped in the microparticles with trapping efficiencies up to 76%, loading level 10% w/v, and particle size 3 microm. Release profiles of 5-FU loaded microparticles were determined to follow a first-order-time relationship. An optimized preparation of 5-FU microparticles was achieved and was capable of controlling the release of 5-FU over 21 days with an in vitro delivery rate of 0.4 microg 5-FU/mg particles/day in the study. Preliminary animal studies indicated that the 5-FU loaded microparticles as an ocular delivery system showed no ocular toxicity and no significant inflammatory response in rabbits for 2 months. The 5-FU loaded microparticles approach, with PLG, might be a potential for the application of long-term delivery of hydrophilic drugs in the eye.

Animals↗

PubMed1996

Preparation and characterization of a biodegradable microparticle antigen/cytokine delivery system.

Biodegradable microparticles (MPs) were prepared to contain dinitrophenylated bovine serum albumin (DNP-BSA) and the cytokines interleukin (IL)-5 and IL-6. The conformational integrity of these MPs was examined by scanning electron microscopy. DNP-BSA was evaluated, postentrapment, by a bicinchoninic acid assay, SDS-PAGE, isoelectric focusing, Western blotting, ELISA and spectrophotometric analysis. The bioactivity of the ILs postentrapment was measured using bioassays. Ocular-topical (OT) and intraperitoneal (IP) administration of loaded MPs induced serum IgG, tear IgA and vaginal wash (VW) IgA responses which persisted up to 45 days post secondary immunization (P2o). OT and IP delivery elicited serum IgG and tear IgA responses up to 140 days post tertiary immunization (P3o). VW IgA responses persisted up to 45 days and 140 days P3o OT and IP delivery, respectively. Overall, the inclusion of cytokines in antigen containing MPs enhanced tear IgA antibody levels following OT delivery P2o, while elevated VW IgA responses occurred following IP delivery P2o and P3o. These data demonstrate that antigen/cytokine loaded MPs can potentiate long-term mucosal antibody responses at both target and distal effector sites as well as elicit circulating antibodies.

Administration, Topical↗

PubMed2006

A biodegradable delivery system for antibiotics and recombinant human bone morphogenetic protein-2: A potential treatment for infected bone defects.

To produce an osteogenic and bacteriocidal biomaterial for the treatment of infected nonunions or bone defects, a synthetic degradable block copolymer of poly-D,L-lactic acid segments with randomly inserted p-dioxanone and polyethylene glycol (PLA-DX-PEG) segments was mixed with recombinant human BMP-2 (rhBMP-2) and antibiotics at high concentration. We then examined the in vitro elution profile of an antibiotic (teicoplanin) from the polymer, the effects of antibiotics on the bone-inducing capacity of rhBMP-2 or on ectopic new bone formation induced by the rhBMP, and the ability of the polymer to repair bone in a rat cranial defect model. Approximately 40% of teicoplanin was released within the first 24 h, with the remaining amount released steadily over 21 days with no loss of antibacterial activity. The polymer had disappeared by degradation in the phosphate buffered saline (pH 7.4) at the end of the incubation period. The in vivo performance of pellets with antibiotics and rhBMP-2 revealed no significant change in bone yield within the ossicles after 3 weeks. Also, antibiotics had no inhibitory effect on the ability of rhBMP2 to repair cranial defects. Indeed, when the defect was filled by a polymer disc loaded with rhBMP-2 with or without teicoplanin, the defect was repaired by new bone, and normal anatomy was restored within 6 weeks. In conclusion, the PLA/DX/PEG polymer appears to work as effectively for antibiotics as it does for rhBMP-2. Additionally, the biological activity of rhBMP-2 was retained irrespective of the presence of antibiotics.

Absorbable Implants↗

PubMed2004

A protein delivery system: biodegradable alginate-chitosan-poly(lactic-co-glycolic acid) composite microspheres.

In the present study we developed alginate-chitosan-poly(lactic-co-glycolic acid) (PLGA) composite microspheres to elevate protein entrapment efficiency and decrease its burst release. Bovine serum albumin (BSA), which used as the model protein, was entrapped into the alginate microcapsules by a modified emulsification method in an isopropyl alcohol-washed way. The rapid drug releases were sustained by chitosan coating. To obtain the desired release properties, the alginate-chitosan microcapsules were further incorporated in the PLGA to form the composite microspheres. The average diameter of the composite microcapsules was 31+/-9microm and the encapsulation efficiency was 81-87%, while that of conventional PLGA microspheres was just 61-65%. Furthermore, the burst releases at 1h of BSA entrapped in composite microspheres which containing PLGA (50:50) and PLGA (70:30) decreased to 24% and 8% in PBS, and further decreased to 5% and 2% in saline. On the contrary, the burst releases of conventional PLGA microspheres were 48% and 52% in PBS, respectively. Moreover, the release profiles could be manipulated by regulating the ratios of poly(lactic acid) to poly(glycolic acid) in the composite microspheres.

Alginates↗

PubMed2004

The efficacy of a hydroxyapatite composite as a biodegradable antibiotic delivery system.

Local biodegradable carriers have been studied for use as a skeletal drug delivery system. This study investigated the efficacy of a local biodegradable composite composed of hydroxyapatite, plaster of Paris, and chitosan impregnated with antibiotics to treat methicillin-resistant Staphylococcus aureus. The composite, impregnated with vancomycin, fosfomycin, or sodium fusidate was tested for its sustained elution characteristics during 3 months and compared with similarly impregnated polymethylmethacrylate using the modified disc diffusion technique. Physicochemical properties using scanning electron microscopy and xray diffraction analysis of each preparation also were analyzed. Vancomycin and fosfomycin incorporated into the hydroxyapatite composite inhibited the organism for 3 months, whereas sodium fusidate was effective only for 3 weeks. Vancomycin and fosfomycin loaded into the hydroxyapatite composite had a significantly better inhibitive effect than when loaded in polymethylmethacrylate, whereas sodium fusidate loaded in polymethylmethacrylate showed a significantly better inhibitive effect than when loaded in the hydroxyapatite composite. Scanning electron microscopy and xray diffraction analysis elucidated the patterns of each drug release profile. The local hydroxyapatite composite is a promising local biodegradable delivery system for vancomycin and fosfomycin, whereas PMMA is a better carrier for sodium fusidate in treating methicillin-resistant staphylococcus aureus osteomyelitis.

Anti-Bacterial Agents↗

PubMed2004

Biodegradable polymers and their potential use in parenteral veterinary drug delivery systems.

Biodegradable polymers have been extensively studied for numerous drug delivery systems for human health purposes. The ever-increasing value of animals to human society allows the application of pharmaceutical developments in the veterinary field from those developed in human medicine. Although many similarities between the human and animal health industries exist there are also notable differences. This paper provides an insight into the animal health market with regard to the challenges and special considerations associated with veterinary drug delivery. It also gives an overview of biodegradable polymers that are used or have been tested in the veterinary field. The purpose of this paper is to highlight some recent developments in this area and to investigate the directions in which veterinary pharmaceutics is heading. In particular, examples of existing biodegradable veterinary drug delivery systems are presented together with applications including intravaginal devices, injectables and implantable systems.

Animals↗

PubMed2005

[Environmental stimuli-sensitive biodegradable drug delivery systems].

Environmental stimuli-sensitive biodegradable drug delivery systems are drawing more and more attentions because of their advantages such as smart properties, high efficiency and easy-to-handle properties. On the basis of a large quantity of references on this topic, a review has been made on the developments of the thermosensitive and pH-sensitive intelligent polymeric systems for drug delivery.

Biocompatible Materials↗

PubMed2005

Bioadhesive interaction and hypoglycemic effect of insulin-loaded lectin-microparticle conjugates in oral insulin delivery system.

Biodegradable microparticles were prepared with alginate by the piezoelectric ejection process, and lectin (wheat germ agglutinin, WGA) was conjugated to alginate microparticles to take advantage of the protective effects of alginate microparticles and the mucoadhesive properties of WGA for improved oral delivery of insulin. Their specific interaction with model mucin was determined by pig mucin (PM) immobilized surface plasmon resonance (SPR) biosensor and in vitro adsorption studies. The hypoglycemic effects of alginate and WGA-conjugated alginate microparticles were examined after oral administration in streptozotocin-induced diabetic rats. The alginate microparticles were fabricated by ejecting alginate/insulin solution into 0.1 M CaCl2 solution through a nozzle actuated by the piezoelectric transducer. The WGA was conjugated to alginate microparticles by activating hydroxyl groups with carbonyldiimidazole (CDI). The affinity constant (K(A)) of alginate-WGA microparticles from the SPR data (K(A)=5.455 g(-1) L) was about nine times greater than alginate microparticles (K(A)=0.628 g(-1) L). In vitro experiments in the mucin solution showed that the conjugated WGA enhanced the interaction about three times. In vivo studies with diabetic rats showed that the blood glucose level of SPF rats was lowest when alginate-WGA microparticles were orally administered. Larger K(A) of alginate-WGA microparticles resulted in larger glucose change (%) from base level. Still, it is not clear whether the transport of insulin through the intestinal mucous membrane was influenced by the increase of residence time at intestinal membrane through the specific adsorption of WGA-conjugated microparticles. However, it is concluded that alginate-WGA microparticles enhance the intestinal absorption of insulin sufficient to drop the glucose level of blood.

Adhesives↗

PubMed1999

New biodegradable polymers for injectable drug delivery systems.

Many biodegradable polymers were used for drug delivery and some are successful for human application. There remains fabrication problems, such as difficult processability and limited organic solvent and irreproducible drug release kinetics. New star-shaped block copolymers, of which the typical molecular architecture is presented, results from their distinct solution properties, thermal properties and morphology. Their unique physical properties are due to the three-dimensional, hyperbranched molecular architecture and influence microsphere fabrication, drug release and degradation profiles. We recently synthesized thermosensitive biodegradable hydrogel consisting of polyethylene oxide and poly(L-lactic acid). Aqueous solution of these copolymers with proper combination of molecular weights exhibit temperature-dependent reversible sol-gel transition. Desired molecular arrangements provide unique behavior that sol (at low temperature) form gel (at body temperature). The use of these two biodegradable polymers have great advantages for sustained injectable drug delivery systems. The formulation is simple, which is totally free of organic solvent. In sol or aqueous solution state of this polymer solubilized hydrophobic drugs prior to form gel matrix.

Animals↗

PubMedDate not supplied

Biodegradable drug delivery systems for gentamicin release and treatment of synovial membrane infection.

OBJECTIVE: This study investigated two biodegradable drug delivery systems (BDDS) for elution of gentamicin and elimination of synovial membrane infection. STUDY DESIGN: The effect of BDDS on control and infected synovial explants was determined. ANIMALS OR SAMPLE POPULATION: Synovial explants from four adult equine cadavers. METHODS: First, BDDS were placed in phosphate buffered saline for 14 days. Eluent was tested for gentamicin concentration (G) and bioactivity. Second, synovial explants were divided into four groups (n = 14/group): Group 1 (control); Group 2 (infected control) 405 cfu Staphylococcus aureus added at 6 hours; Group 3 (antibiotic BDDS [Ab-BDDS]) Ab-BDDS added at 24 hours; Group 4 (infected Ab-BDDS) 405 cfu S. aureus added at 6 hours, Ab-BDDS added at 24 hours. Both types of Ab-BDDS were used (n = 7/type/group). Explants were incubated in standard medium for 4 days. Medium was cultured and analyzed for (G) and hyaluronic acid concentration (HA). Explants were analyzed for viability and morphologic changes. RESULTS: The Ab-BDDS released >500 microg/mL of active gentamicin for 10 days. In Group 3, infection was eliminated within 24 hours, but histologic scores did not return to normal. Viability was significantly reduced by infection, but if eliminated, viability tended to return to normal. In Group 3, the Ab-BDDS had no significant effect on viability or (HA). Histopathologic scores were significantly higher for infected synovium. Infection, even if treated, significantly reduced (HA). CONCLUSIONS: Both Ab-BDDS eliminated infection within 24 hours. However, synovial morphology, viability and function did not return to normal. CLINICAL RELEVANCE: The Ab-BDDS may be useful for treatment of synovial membrane infection.

Absorbable Implants↗

PubMed2002

Intestinal drug delivery systems with biodegradable microspheres targeting mucosal immune-regulating cells for chronic inflammatory colitis.

We developed two kinds of delivery systems targeting mucosal immune regulating cells with poly (D,L-lactic acid) microspheres containing dexamethasone and dichloromethylene diphosphonate, and gelatine microspheres containing interleukin-10. To estimate the efficacy of these drug delivery systems, we studied the effects on experimental colitis induced by dextran sodium sulfate, 2,4,6-trinitrobenzene sulfonic acid, and interleukin-10-deficient mice. Intestinal administration of these microspheres significantly improved colitis with decreased histological score, myeloperoxidase activity, and nitric oxide production compared with mice treated with free agents. Gene expressions of tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma were down-regulated in treated animals. Serum Dx, IL-10 levels, and systemic macrophages were unchanged after treatment. Our findings suggest that local macrophages in the intestine play a critical role in the initiation of chronic colitis in the animal model of inflammatory bowel disease (IBD). Intestinal drug delivery systems with biodegradable microspheres targeting mucosal immune-regulating cells may become a therapeutic approach to human IBD.

Animals↗

PubMed1998

Development of a sustained-release biodegradable polymer delivery system for site-specific delivery of oligonucleotides: characterization of P(LA-GA) copolymer microspheres in vitro.

Development of a Sustained-Release Biodegradable Polymer Delivery System for Site-Specific Delivery of Oligonucleotides: Characterization of P(LA-GA) Copolymer Microspheres In Vitro Antisense oligodeoxynucleotides (ODNs) can selectively inhibit individual gene expression provided they gain access to and remain stable at the target site for a sufficient period of time. Biodegradable sustained-release delivery systems may facilitate site-specific delivery and also prevent degradation of ODNs by nucleases whilst delivering the nucleic acid in a controlled manner to the desired site of action. In this study, we have characterized biodegradable poly (lactide-co-glycolide) (P(LA-GA)) 50:50 microspheres for the potential delivery of antisense oligonucleotides in vivo. Phosphodiester (PO) oligonucleotides complementary to either c-myc proto-oncogene or the tat gene in HIV-RNA were adequately incorporated within P(LA-GA) microspheres with entrapment efficiencies up to 60% depending on particles size. In vitro release profiles of antisense nucleic acids from 10-20 microm size microspheres over 56 days in physiological buffer were triphasic. Profiles were characterised by an initial burst effect during the first 48 hours (phase 1) of release followed by a more sustained release (phase 2) with an additional increased release (phase 3) being observed after 25 days which corresponded with bulk degradation of the copolymer matrix. The release profiles were influenced by microsphere size, copolymer molecular weight, ODN loading, ODN length and by the pH of release medium used. The serum stability of PO ODNs was significantly improved when entrapped within P(LA-GA) microspheres and the hybridization capability, as assessed by duplex melting (Tm) measurements, of released ODN was not impaired by the double-emulsion microsphere fabrication procedure used. Thus, P(LA-GA) microspheres appear to be promising candidates for improving site-specific delivery profiles for ODNs and are worthy of further evaluation in vivo.

Base Sequence↗

PubMed2004

Biodegradable radiation delivery system utilizing glass microspheres and ethylenediaminetetraacetate chelation therapy.

Dysprosium lithium-borate (DyLB) glass microspheres have been developed as a biodegradable radiation delivery vehicle for the treatment of rheumatoid arthritis and other diseases. Radioactive microspheres of these glasses are intended to be injected into a joint infected with rheumatoid arthritis to safely deliver a localized dose (100 Gy) of beta radiation. Once injected, the microspheres react nonuniformly with body fluids. The nonradioactive, lithium-borate component is dissolved from the glass, whereas the radioactive (165)Dy reacts with phosphate anions in the body fluids, and becomes "chemically" trapped in a solid, dysprosium phosphate reaction product that has the same size as the unreacted microsphere. The glass microspheres lose approximately 80% of their weight after nonuniform reaction (<1 day), but the dysprosium phosphate reaction product is slowly metabolized by the body over several months. Ethylenediaminetetraacetate (EDTA) chelation therapy can be used to dissolve the dysprosium phosphate reaction product in vitro in <2 h. The dysprosium phosphate reaction product which formed in vivo in the joint of a Sprague-Dawley rat was also dissolved by EDTA chelation therapy in <1 week, without causing any detectable joint damage. The combination of DyLB glass microspheres and EDTA chelation therapy provides a unique "tool" for the medical community because it can deliver a large dose (>100 Gy) of localized beta radiation to a treatment site within the body, followed by complete biodegradability.

Animals↗

PubMed1999

Development of biodegradable drug delivery system to treat addiction.

Opiate addiction is a serious problem that has now spread worldwide to all levels of society. Buprenorphine has been used for several years for the treatment of opiate addiction. The objective of this project was to develop sustained-release biodegradable microcapsules for the parenteral delivery of buprenorphine. Biodegradable microcapsules of buprenorphine/poly(lactide-co-glycolide) were prepared using two main procedures based on an in-water drying process in a complex emulsion system. These procedures differ in the way the organic solvent was eliminated: evaporation or extraction. The effect of drug loading and the effect of partial saturation of the aqueous phase with the core material during the in-water solvent evaporation were also studied. The efficiency of encapsulation increased from 11% to 34% when the drug loading was decreased from 20% to 5%. There was no significant change in the efficiency of encapsulation when the aqueous phase was partially saturated with buprenorphine. In changing the solvent removal process from evaporation to extraction, no significant change in the efficiency of encapsulation was observed. The microcapsules prepared by the solvent evaporation were smooth and spherical. However, the microcapsules prepared by the extraction of the organic solvent lost their surface smoothness and became slightly irregular and porous compared with the other batches. The average particle size of the microcapsules was between 14 and 49 microns. The cumulative drug release was between 2% and 4% within the first 24 hr. A sustained drug release continued over 45 days.

Absorbable Implants↗

PubMed2006

Biodegradable scaffolds--delivery systems for cell therapies.

The use of cells as therapies for disease, repair and regeneration of tissues is one of the new challenges in modern therapeutics. To facilitate the ability to localise, condition and protect cells, biodegradable scaffolds are being developed that will improve the efficiency of these treatments. Thus, cell delivery systems, either scaffolds or capsules, play a pivotal role in the success of these techniques. This review discusses these novel approaches. The selection of scaffold materials is addressed alongside issues of biocompatibility. The current research developments in smart scaffolds, which focus on the formation of biomimetic scaffolds, new fabrication techniques capable of controlling architecture and microstructure of scaffolds, and the production of injectable and in situ crosslinked scaffolds, are outlined. Finally, the continuing challenges that will drive future research in the cell therapies are highlighted.

Animals↗