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 649 records · Page 36Linked to original sources
PubMed2002

Precise control of PLG microsphere size provides enhanced control of drug release rate.

An important limitation in the development of biodegradable polymer microspheres for controlled-release drug delivery applications has been the difficulty of specifically designing systems exhibiting precisely controlled release rates. Because microparticle size is a primary determinant of drug release, we developed a methodology for controlling release kinetics employing monodisperse poly(D,L-lactide-co-glycolide) (PLG) microspheres. We fabricated 20-, 40- and 65-microm diameter rhodamine-containing microspheres and 10-, 50- and 100-microm diameter piroxicam-containing microspheres at various loadings from 1 to 20%. In vitro release kinetics were determined for each preparation. Drug release depended strongly on microsphere diameter with 10- and 20-microm particles exhibiting concave-downward release profiles while larger particles resulted in sigmoidal release profiles. Overall, the rate of release decreased and the duration increased with increasing microsphere size. Release kinetics from mixtures of uniform microspheres corresponded to mass-weighted averages of the individual microsphere release kinetics. Appropriate mixtures of uniform microspheres were identified that provided constant (zero-order) release of rhodamine and piroxicam for 8 and 14 days, respectively. Mixing of uniform microspheres, as well as control of microsphere size distribution, may provide an improved methodology to tailor small-molecule drug-release kinetics from simple, biodegradable-polymer microparticles.

Biocompatible Materials↗
PubMed1991

Biodegradable and biocompatible poly(DL-lactide-co-glycolide) microspheres as an adjuvant for staphylococcal enterotoxin B toxoid which enhances the level of toxin-neutralizing antibodies.

Microspheres composed of biocompatible, biodegradable poly(DL-lactide-co-glycolide) (DL-PLG) and staphylococcal enterotoxin B (SEB) toxoid were evaluated as a vaccine delivery system when subcutaneously injected into mice. As measured by circulating immunoglobulin G (IgG) antitoxin titers, the delivery of SEB toxoid via DL-PLG microspheres, 1 to 10 microns in diameter, induced an immune response which was approximately 500 times that seen with nonencapsulated toxoid. The kinetics, magnitude, and duration of the antitoxin response induced with microencapsulated toxoid were similar to those obtained when an equal toxoid dose was administered as an emulsion with complete Freund adjuvant. However, the microspheres did not induce the inflammation and granulomata formation seen with complete Freund adjuvant. The adjuvant activity of the microspheres was not dependent on the superantigenicity of SEB toxin and was equally effective at potentiating circulating IgG antitrinitrophenyl levels in response to microencapsulated trinitrophenyl-keyhole limpet hemocyanin. Empty DL-PLG microspheres were not mitogenic, and SEB toxoid injected as a mixture with empty DL-PLG microspheres was no more effective as an immunogen than toxoid alone. Antigen-containing microspheres 1 to 10 microns in diameter exhibited stronger adjuvant activity than those greater than 10 microns, which correlated with the delivery of the 1- to 10-microns, but not the greater than 10-microns, microspheres into the draining lymph nodes within macrophages. The antibody response induced through immunization with microencapsulated SEB toxoid was protective against the weight loss and splenic V beta 8+ T-cell expansion induced by intravenous toxin administration. These results show that DL-PLG microsphere vaccine delivery systems, which are composed of pharmaceutically acceptable components, possess a strong adjuvant activity for their encapsulated antigens.

Adjuvants, Immunologic↗
PubMed1990

Antitumor effects of a new interleukin-2 slow delivery system on methylcholanthrene-induced fibrosarcoma in mice.

The interleukin-2 (IL-2) mini-pellet, the carrier material of which is a biocompatible and biodegradable atelocollagen refined from bovine skin, contains 1 x 10(6) units of IL-2 and can release IL-2 slowly in vivo by diffusion and dissolution. We have evaluated the antitumor effects of the IL-2 mini-pellet on an established solid murine tumor, methylcholanthrene-induced fibrosarcoma (Meth A). The subcutaneous administration of the IL-2 mini-pellet alone on days 8 and 11 after tumor inoculation significantly inhibited tumor growth. A significant inhibition was also seen when it was combined with the intravenous injection of 5 x 10(7) lymphokine-activated killer (LAK) cells, in comparison to the untreated controls. Moreover, therapy with the IL-2 mini-pellet alone or in combination with LAK cells also prolonged the survival of mice bearing Meth A fibrosarcoma. In order to determine the precise mechanism of action of these antitumor effects, we tested splenocytes of treated mice for cytotoxic activity in vitro and investigated tumor tissues by an immunohistochemical method. On day 2 after the administration of the IL-2 mini-pellet, the lytic activity of splenocytes against both YAC-1 and JTC-11 cells (i.e. NK and LAK activity) was significantly augmented, and on day 7 a massive accumulation of lymphocytes, which were mainly like Thy1+ and/or asialo-GM1+ LAK cells, was seen in the tumor. These findings indicate that the IL-2 mini-pellet is an appropriate system for local administration of IL-2 and can induce LAK-like effector cells at the target site.

Animals↗
PubMed2005

Efficacy of an intratumoral controlled release formulation of clusterin antisense oligonucleotide complexed with chitosan containing paclitaxel or docetaxel in prostate cancer xenograft models.

PURPOSE: To develop and evaluate an injectable, controlled release delivery system for a phosphorothioate antisense oligonucleotide (ASO) based on complexed ASO:chitosan dispersed in a biodegradable polymeric paste for intratumoral treatment of solid tumors. METHODS: Clusterin ASO was complexed with chitosan particles and incorporated into a paste based on a 60:40 blend of methoxy-poly(ethylene glycol) (MePEG) and triblock copolymer of poly(D: ,L: -lactic acid-co-caprolactone)-PEG-(D: ,L: -lactic acid-co-caprolactone). In vitro release profiles of clusterin ASO into phosphate-buffered saline at 37 degrees C were obtained under sink conditions and assayed by anionic exchange high-performance liquid chromatography. In vivo efficacy studies were carried out in human prostate PC-3 and LNCaP tumors grown subcutaneously in mice. Paste formulations of clusterin ASO with or without paclitaxel or docetaxel were injected intratumorally and tumor volumes and serum prostate specific antigen (PSA) levels were measured. RESULTS: Controlled release of clusterin ASO was obtained over several weeks. The rate and extent of ASO release was proportional to the ratio of ASO to chitosan in the paste. Treatment of mice bearing PC-3 tumors with clusterin ASO plus paclitaxel or docetaxel paste had reduced mean tumor volume by greater than 50% at 4 weeks. Treatment of mice bearing LNCaP tumors with clusterin ASO plus paclitaxel reduced mean tumor volume and serum PSA level by more than 50% and 70%, respectively. CONCLUSIONS: Complexation of clusterin ASO with chitosan and incorporation into polymeric paste with paclitaxel or docetaxel produced in vitro controlled release of the ASO and in vivo efficacy over 4 weeks following a single intratumoral injection in solid human prostate tumors in mice.

Adenocarcinoma↗
PubMed2006

Layer-by-layer polyelectrolyte coating of low molecular weight poly(lactic acid) nanoparticles.

Low molecular weight (M(w)) poly(L-lactic acid) (PLA) nanoparticles were coated with polyelectrolytes (PEs) by layer-by-layer (LbL) technique using a filtration approach. Poly(allylamine hydrochloride) and poly(sodium 4-styrenesulfonate) were applied as PEs in coating. LbL coating is aimed to use in producing (nano)particulate drug delivery systems with improved biocompatibility and sustained or targeted release of drug substances. Nanoparticles of rapidly biodegradable polymers, like the low M(w) PLA, open up a possibility to control the release of the encapsulated substance by the coating, but set challenges to the coating process due to increased aggregation tendency and degradation rate of the polymer. When the core PLA nanoparticles were prepared by nanoprecipitation, surface properties of the nanoparticles were affected by solvent selection. Successful LbL coating of the PLA nanoparticles was obtained only with chloroform, but not with dichloromethane as the solvent during nanoprecipitation. Reason for this was found to be the more charged surface of the nanoparticles prepared with chloroform compared to the nanoparticles prepared with dichloromethane.

Electrolytes↗
PubMed2003

Localized insulin-like growth factor I delivery to enhance new bone formation.

Insulin-like growth factor I (IGF I) exerts an important role during skeletal growth and bone formation. Therefore, its localized delivery appears attractive for the treatment of bone defects. To prolong IGF I delivery, we entrapped the protein into biodegradable poly(lactide-co-glycolide) microspheres (PLGA MS) and evaluated the potential of this delivery system for new bone formation in two defect models of ovine long bones, i.e., a 8-mm methaphyseal drill hole and a 10-mm segmental tibia defect. Administration of 100 microg of IGF I in PLGA MS resulted in new bone formation within 3 weeks in the drill hole and bridging of the segmental defect within 8 weeks. The observed increase of 12% newly formed bone in the drill hole defect after 3 weeks was substantial, compared to the measured morphometric bone-to-total area ratio of 31% bone in normal cancellous bone. Bone regeneration was further explored by measuring gene expression of typical markers for local mediators and growth factors by real-time polymerase chain reaction. Inflammation was reduced in presence of IGF I and this in vivo observation was corroborated in vitro by quantifying gene expression of inflammatory proteins and by assessing the activation of the NF-kappaB pathway, playing an important role in the regulation of inflammation. Administration of the IGF I delivery system downregulated inflammatory marker gene expression at the site of bone injury, induced new bone formation and reduced bone resorption, and resulted in bridging of 10-mm segmental tibial defects within 8 weeks.

Animals↗
PubMed1988

Aliphatic polyesters and cellulose-based polymers for controlled release applications.

The general technologies for fabricating drug delivery systems are briefly discussed in the present review. Furthermore, two types of commonly used polymers, biodegradable aliphatic polyesters for parenteral administration and cellulose-based polymers for oral uses, are presented by means of selected examples of their properties and applications to control drug release.

Cellulose↗
PubMed1993

AUR Memorial Award 1993. A drug system (PDH) for interventional radiology. Synthesis, properties, and efficacy.

RATIONALE AND OBJECTIVES: The authors synthesized and tested a novel hydrogel system proposed for use in extra- and intravascular radiologic interventions, such as chemoembolizations and embolizations, and as a vehicle for sustained drug release. MATERIALS: The material was specifically designed to meet the prerequisites of biodegradation, biocompatibility, low immunogenicity, low toxicity, and easy use. The material consists of a protein backbone cross-linked with activated bifunctional polyethyleneglycol (PEG) derivatives (PEG-derivatized hydrogel, [PDH]) to which are attached therapeutic (e.g., doxorubicin, a chemotherapeutic agent = PDH-dx) or diagnostic labels (e.g. Gd-DTPA). RESULTS: PDH-dx effectively reduced the risk of local tumor recurrence in a rat model when implanted locally after surgical tumor removal. After administration, PDH is degraded by proteases release from macrophages; implantations of 1 mL samples into paraspinal muscles of rats were completely absorbed within 4 weeks and its constituents were metabolized. Antibody titers (total Ig response) against the PDH were not detectable 1 week after implantation, whereas protein control substances elicited a strong response. CONCLUSIONS: PDH and its derivatives are relatively nontoxic, biodegradable materials for use in radiologic interventions and as a vehicle for sustained drug release.

Animals↗
PubMed2003

Local delivery of minocycline and systemic BCNU have synergistic activity in the treatment of intracranial glioma.

Minocycline, a tetracycline derivative, has been shown to inhibit tumor angiogenesis through inhibitory effects on matrix metalloproteinases. Previous studies have shown this agent to be effective against a rodent brain tumor model when delivered intracranially and to potentiate the efficacy of standard chemotherapeutic agents. In the present study, the in vivo efficacy of intracranial minocycline delivered by a biodegradable controlled-release polymer against rat intracranial 9L gliosarcoma was investigated to determine whether it potentiates the effects of systemic 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU). Minocycline was incorporated into the biodegradable polymer polyanhydride poly[bis(p-carboxyphenoxy)propane-sebacic acid] (pCPP:SA) at a ratio of 50:50 by weight. The release kinetics of minocycline from the polymer were assessed. For the efficacy studies, female Fischer 344 rats were implanted with 9L glioma. Treatment with minocycline delivered by the pCPP:SA polymer at the time of tumor implantation resulted in 100% survival in contrast to untreated control animals that died within 21 days. Treatment with the minocycline-polymer 5 days after tumor implantation provided only modest increases in survival. The combination of intracranial minocycline and systemic BCNU extended median survival by 82% compared to BCNU alone (p < 0.0001) and 200% compared to no treatment (p < 0.004). We conclude that local intracranial delivery of minocycline from biodegradable controlled-release polymers inhibits tumor growth and may have clinical utility when combined with a chemotherapeutic agent.

Absorbable Implants↗
PubMed2006

The use of soluble polymers and polymer microparticles to provide improved vaccine responses after parenteral and mucosal delivery.

It is important when developing new vaccine systems to give proper attention to the question of delivery. In some cases the judicious choice of a delivery system can provide a greatly enhanced immune response and avoid the need to use a vaccine adjuvant. Delivery systems that have been developed originally for the administration of challenging drug can be used with success for vaccines. Polymer microspheres and lamellar particle based on the biodegradable materials polylactide and polylactide co-glycolide can be employed for the improved parenteral and mucosal administration of antigens. Likewise soluble biopolymers such as chitosan can be used for the improved nasal delivery of various antigens as well as DNA. Results from animal studies and recent clinical trials are provided.

Absorbable Implants↗
PubMed1998

Colonic drug targeting.

Specific targeting of drugs to the colon is recognized to have several therapeutic advantages. Drugs which are destroyed by the stomach acid and/or metabolized by pancreatic enzymes are slightly affected in the colon, and sustained colonic release of drugs can be useful in the treatment of nocturnal asthma, angina and arthritis. Treatment of colonic diseases such as ulcerative colitis, colorectal cancer and Crohn's disease is more effective with direct delivery of drugs to the affected area. Likewise, colonic delivery of vermicides and colonic diagnostic agents require smaller doses. This article is aimed at providing insight into the design considerations and evaluation of colonic drug delivery systems. For this purpose, the anatomy and physiology of the lower gastrointestinal tract are surveyed. Furthermore, the biopharmaceutical aspects are considered in relation to drug absorption in the colon and hence various approaches to colon-specific drug delivery are discussed.

Biodegradation, Environmental↗
PubMed1994

Biodegradable long-circulating polymeric nanospheres.

Injectable nanoparticulate carriers have important potential applications such as site-specific drug delivery or medical imaging. Conventional carriers, however, cannot generally be used because they are eliminated by the reticulo-endothelial system within seconds or minutes after intravenous injection. To address these limitations, monodisperse biodegradable nanospheres were developed from amphiphilic copolymers composed of two biocompatible blocks. The nanospheres exhibited dramatically increased blood circulation times and reduced liver accumulation in mice. Furthermore, they entrapped up to 45 percent by weight of the drug in the dense core in a one-step procedure and could be freeze-dried and easily redispersed without additives in aqueous solutions.

Animals↗
PubMed2003

Evaluation of gliadins nanoparticles as drug delivery systems: a study of three different drugs.

In this paper, biopolymer nanoparticles are studied, which unlike many synthetic carriers used for controlled release, are biocompatible and biodegradable systems. Gliadins nanoparticles are obtained by a desolvatation method, also known as drawning-out precipitation. These particles have been shown to be interesting as drug release systems for all-trans-retinoic acid. The aim of this paper was to study the influence of the polarity of different drugs on nanoparticle characteristics such as size and drug loading efficiency. Three drugs of three different polarities were studied: the hydrophobic Vitamin E (VE), the slightly polar mixture of linalool and of linalyl acetate (LLA) and the cationic amphiphilic benzalkonium chloride (BZC). This comparative work shows that the amount of the entrapped VE and LLA is higher than that of the cationic BZC, confirming a strong interaction between gliadins and apolar compounds, due to the apolarity of the proteins. This interaction results in a low diffusion coefficient and a partition coefficient in favour of gliadins, resulting in a low permeability coefficient. The drug release kinetics of two substances, LLA and BZC, are observed, in showing a burst effect, then a diffusion process, which can be modelled assuming that the particles are homogeneous spheres.

Acyclic Monoterpenes↗
PubMed1995

Immunization with a soluble recombinant HIV protein entrapped in biodegradable microparticles induces HIV-specific CD8+ cytotoxic T lymphocytes and CD4+ Th1 cells.

One of the major obstacles to the development of successful recombinant vaccines against human immunodeficiency virus (HIV) and other intracellular pathogens is the identification of a safe and effective vaccine delivery system for the induction of cell mediated immunity with soluble protein antigens. In this study it was demonstrated that immunization with a recombinant HIV envelop (env) protein entrapped in biodegradable poly(lactide-co-glycolide) (PLG) microparticles induced consistent HIV-specific CD4+ and CD8+ T-cell responses in mice. Major histocompatibility complex (MHC) class I-restricted cytotoxic T lymphocytes (CTL) responses were detected following a single systemic immunization with gp120 entrapped microparticles and when given by the intranasal (i.n.) route induced HIV-specific CD8+ CTL and secretory IgA. Furthermore immunization with gp120 entrapped in microparticles generated CD4+ T cells that secreted moderate to high levels of IFN-gamma. Therefore, PLG microparticles are a safe and effective means of delivering antigen to the appropriate processing site for the generation of class I-restricted CTL, and are also capable of inducing Th1 cells.

Animals↗
PubMed2003

[Researches on PEG-modified copolymer nanoparticle].

Biodegradable polymeric nanoparticles acting as drug carrier have important potential applications such as site-specific drug delivery and controllable drug delivery. However, these carriers cannot generally be used because they are eliminated by the reticulo-endothelial system within seconds or minutes after intravenous injection. To overcome this limitation, more and more researchers introduce hydrophilic polyethylene glyeol(PEG) to modify polymeric nanoparticles for avoiding their uptake by reticulo-endothelial system. Introducing PEG not only changes polymer nanoparticles' biodegradation in vivo, but also influences drug's properties such as drug release, in vivo biodistribution, et. al. In this paper are reviewed the researches of PEG-modified copolymer nanoparticles, including their preparation and size distribution, stability, drug incorporation, drug release, in vivo biodistribution, in vitro cytotoxicty. A prospect for the researches and developments of the PEG-modified copolymer nanoparticles was also made.

Animals↗
PubMed1995

In vitro degradation and release characteristics of biodegradable implants containing trypsin inhibitor.

The use of a biodegradable implant system that provides a steady, controlled release of drugs or bioactive factors can be an attractive delivery vehicle of substances that can enhance repair processes in the musculoskeletal system. The present in vitro study examined the degradative characteristics and release kinetics of a 50 to 50 polylactic acid/polyglycolic acid implant, used as a carrier of trypsin inhibitor, during a 10-week period. Morphological and scanning electron microscopic examinations demonstrated that the implant degraded in a gradual, extended fashion such that by 10 weeks the implant was completely dissolved. It also was shown that the protein was released from the implant in a sigmoidal fashion with increased release between 3 and 7 weeks. More than 95% of the trypsin inhibitor originally incorporated in the implants was released during the 10-week test period. To describe further the degradation process of the implant, temporal changes in its molecular weight and surface axial strain were determined also. It was shown that in the initial 4 weeks, there was a marked decrease in molecular weight of the implants. Axial strain decreased and then increased over time, suggesting an initial period of stiffening followed by a period of degradative softening.

Biodegradation, Environmental↗
PubMed1998

Design of microencapsulated chitosan microspheres for colonic drug delivery.

Among the different approaches to achieve colon-selective drug delivery, the use of polymers, specifically biodegraded by colonic bacteria, holds great promise. In this work a new system which combines specific biodegradability and pH-dependent release is presented. The system consists of chitosan (CS) microcores entrapped within acrylic microspheres. Sodium diclofenac (SD), used as a model drug, was efficiently entrapped within CS microcores using spray-drying and then microencapsulated into Eudragit L-100 and Eudragit S-100 using an oil-in-oil solvent evaporation method. The size of the CS microcores was small (1.8-2.9 microns) and they were encapsulated within Eudragit microspheres (size between 152 and 233 microns) forming a multireservoir system. Even though CS dissolves very fast in acidic media, at pH 7.4, SD release from CS microcores was delayed, the release rate being adjustable (50% dissolved within 30-120 min) by changing the CS molecular weight (MW) or the type of CS salt. Furthermore, by coating the CS microcores with Eudragit, perfect pH-dependent release profiles were attained. No release was observed at acidic pHs, however, when reaching the Eudragit pH solubility, a continuous release for a variable time (8-12 h) was achieved. A combined mechanism of release is proposed, which considers the dissolution of the Eudragit coating, the swelling of the CS microcores and the dissolution of SD and its further diffusion through the CS gel cores. In addition, infrared (IR) spectra revealed that there was an ionic interaction between the amine groups of CS and the carboxyl groups of Eudragit, which provided the system with a new element for controlling the release. In conclusion, this work presents new approaches for the modification of CS as well as a new system with a great potential for colonic drug delivery.

Chitin↗
PubMed2002

Biodegradable dextran-polylactide hydrogel networks: their swelling, morphology and the controlled release of indomethacin.

Biodegradable polymer hydrogel networks based on hydrophilic dextran derivative of allyl isocyanate (dex-AI) and hydrophobic poly (D,L) lactide diacrylate macromer (PDLLAM) were synthesized, and their swelling and morphological properties were studied. During a 2-day incubation, the higher the PDLLAM composition in the hydrogel, the slower the swelling as well as the lower the extent of swelling were. A 3D porous network structure was observed by scanning electron microscope. The rate of formation of this 3D porous network structure depended on the hydrophilicity of the components, their composition ratio, and the degradation time. The highly hydrophilic dex-AI component facilitated the formation of this 3D porous network structure at an earlier immersion period, while the degradability of the PDLLAM component would make this 3D porous network structure more open at a later immersion period. Indomethacin, a low molecular weight and moderately hydrophobic drug, was incorporated into the hydrogels for the release study in pH 7.4 phosphate buffer solution at 37 degrees C. The release kinetics suggested, as the PDLLAM composition increased, the indomethacin diffusion coefficient (D) and release half life time (t(1/2)) decreased, while the release index n increased. The controlled release mechanism was determined by the combination of three factors: the rate and degree of formation of swelling-induced 3D porous structure in the hydrogel, the hydrolytic degradation of PDLLAM components, and the hydrophobic interaction between PDLLAM and IDM.

Biocompatible Materials↗