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At least 1,207 records · Page 67Linked to original sources
PubMed2005

Size and temperature effects on poly(lactic-co-glycolic acid) degradation and microreservoir device performance.

The component materials of controlled-release drug delivery systems are often selected based on their degradation rates. The release time of a drug from a system will strongly depend on the degradation rates of the component polymers. We have observed that some poly(lactic-co-glycolic acid) polymers (PLGA) exhibit degradation rates that depend on the size of the polymer object and the temperature of the surrounding environment. In vitro degradation studies of four different PLGA polymers showed that 150 microm thick membranes degraded more rapidly than 50 microm thick membranes, as characterized by gel permeation chromatography and mass loss measurements. Faster degradation was observed at 37 degrees C than 25 degrees C, and when the saline media was not refreshed. A biodegradable polymeric microreservoir device that we have developed relies on the degradation of polymeric membranes to deliver pulses of molecules from reservoirs on the device. Earlier molecular release was seen from devices having thicker PLGA membranes. Comparison of an in vitro release study from these devices with the degradation study suggests that reservoir membranes rupture and drug release occurs when a membrane threshold molecular weight of 5000-15000 is reached.

Absorbable Implants↗
PubMedDate not supplied

Controlled release of cisplatin incorporated into biodegradable poly-d, l-lactic acid.

Using a melt-pressing technique, we produced a small solid cylinder containing cisplatin (CDDP) embedded in poly-d, l-lactic acid (CDDP-PLA). The in vitro release of CDDP from the polymer was examined in an immersion system. CDDP was released continuously for more than four weeks with no initial burst. Drug distribution for CDDP-PLA was compared with CDDP solution (CDDP-SOL) by subcutaneous administration into the back of rats. In the CDDP-PLA group, a high concentration of CDDP was maintained in the subcutaneous tissues near the implants for 20 days. However, in the CDDP-SOL group, the concentration of CDDP was low by 10 days after drug administration. CDDP-PLA may become a useful tool in locoregional chemotherapy as a solid type of drug delivery system with longlasting release.

Animals↗
PubMed2000

In vitro bioactivity and gentamicin release from glass-polymer-antibiotic composites.

Composite materials have been prepared from bioactive glass powders in the SiO(2)-CaO-P(2)O(5) system, a biodegradable polymer [poly(L-lactic acid) (PLA)], a biostable polymer [polymethylmethacrylate (PMMA)], and an antibiotic [gentamicin]. The purpose of such composites is to obtain implantable materials that are able to lead to bone growth and also can, at the most critical inflammation-infection step, release an antibiotic. X-ray diffraction, scanning electron microscopy, X-ray energy dispersive spectroscopy, and FTIR analyses after different soaking periods in SBF demonstrated the growth of an apatite-like layer on the composite surface. Therefore the bioactive glass-polymer-antibiotic combination used in this work does not inhibit the glass bioactivity. The release of gentamicin after a soaking of the materials in SBF was followed by UV-visible spectroscopy. A fast initial release during the first 10 h of soaking, followed by a controlled release of the drug was observed.

Apatites↗
PubMed2005

Incorporation of protein-eluting microspheres into biodegradable nerve guidance channels for controlled release.

Nerve guidance channels (NGCs) promote axonal regeneration after transection injury of the peripheral nerve or spinal cord, yet this regeneration is limited. To enhance regeneration further, we hypothesize that localized delivery of therapeutic molecules combined with the NGC is required. In an attempt to achieve such an NGC, we designed and synthesized a novel NGC in which protein-encapsulated microspheres were stably incorporated into the tube wall. Specifically, poly(lactide-co-glycolide) (PLGA 50/50) microspheres were physically entrapped in the annulus between two concentric tubes, consisting of a chitosan inner tube and a chitin outer tube. Taking advantage of the extensive shrinking that the outer chitin tube undergoes with drying, >15 mg of microspheres were loaded within the tube walls. Using BSA-encapsulated microspheres as the model drug delivery system, BSA was released from microsphere loaded tubes (MLTs) for 84 days, and from freely suspended PLGA microspheres for 70 days. An initial burst release was observed for both MLTs and free microspheres, followed by a degradation-controlled release profile that resulted in a higher release rate from MLTs initially, which was then attenuated likely due to the buffering effect of chitin and chitosan tubes. Epidermal growth factor (EGF), co-encapsulated with BSA in PLGA 50/50 microspheres in MLTs, was released for 56 days with a similar profile to that of BSA. Released EGF was found to be bioactive for at least 14 days as assessed by a neurosphere forming bioassay.

Algorithms↗
PubMed2005

Preparation of a hyaluronic acid hydrogel through polyion complex formation using cationic polylactide-based microspheres as a biodegradable cross-linking agent.

A novel hyaluronic acid (HA)-based hydrogel was prepared through polyion complex (PIC) formation between cationic polylactide (PLA)-based microspheres (MS+) and hyaluronic acid (HA-) as an anionic polyelectrolyte. The MS+ and HA formed a biodegradable PIC hydrogel (HA-/MS+) when mixed in aqueous media. The swelling behavior and mechanical properties of the PIC hydrogel could be controlled by changing the charge ratio between HA- and MS+. In addition, the HA-/MS+ PIC hydrogel resulted in a lower inflammatory response compared with a collagen hydrogel in vivo.

Animals↗
PubMed2004

Oligo-3-hydroxybutyrates as potential carriers for drug delivery.

In the present paper we describe the synthesis and toxicity studies of well-defined tailor made oligo-[R,S]-3-hydroxybutyrates (OHBs). The results indicate potential applicability of these nano-polymers as drug delivery carriers. Several OHBs of number average molecular weight (M(n)) ranging from 800 to 2400 have been synthesized and tested on transformed hamster V79 fibroblasts and murine melanoma B16(F10) cells using the 3-[4,5-dimethylthiazol-2-yl]2,5-diphenyltetrazolium bromide (MTT) based drug resistance and clonogenic survival assays. We show that 96-h incubation of cells with 1-9 microg/ml of OHBs did not affect cell viability. Incubation of OHBs with rat hepatoma FTO-2B cells stably transfected with chloramphenicol acetyltransferase (CAT) gene ligated to heat-inducible hsp70i gene promoter demonstrated that OHBs did not induce cellular stress response. Finally, we demonstrate that doxorubicin conjugated with OHB is effectively taken up by murine melanoma B16(F10) cells in vitro and localizes in the cytoplasm. These data show for the first time that tailor-made biodegradable and biocompatible oligomers of 3-hydroxybutyric acid can be taken into consideration as effective, non-toxic vectors for delivery of drugs in a conjugated form.

3-Hydroxybutyric Acid↗
PubMed2002

Genetically engineered silk-elastinlike protein polymers for controlled drug delivery.

The silk-elastinlike class of genetically engineered protein polymers is composed of tandemly repeated silk-like (Gly-Ala-Gly-Ala-Gly-Ser) and elastin-like (Gly-Val-Gly-Val-Pro) amino acid blocks. The precision with which these polymers can be synthesized, as well as the ability to incorporate motifs that allow for gel-formation, stimuli-sensitivity, biodegradation, and biorecognition have stimulated interest in their use for controlled drug and gene delivery. This review will focus on the synthesis and characterization of silk-elastinlike polymers as related to controlled drug delivery. The design and biological synthesis of the copolymers, by recombinant DNA techniques, are reviewed. The characterization of the polymers is discussed. Finally, biocompatibility of the polymers and recent studies to determine their potential utility for controlled drug and gene delivery are reviewed.

Bacterial Proteins↗
PubMedDate not supplied

Neurosurgical delivery of chemotherapeutics, targeted toxins, genetic and viral therapies in neuro-oncology.

Local delivery of biologic agents, such as gene and viruses, has been tested preclinically with encouraging success, and in some instances clinical trials have also been performed. In addition, the positive pressure infusion of various therapeutic agents is undergoing human testing and approval has already been granted for routine clinical use of biodegradable implants that diffuse a chemotherapeutic agent into peritumoral regions. Safety in glioma patients has been shown, but anticancer efficacy needs additional refinements in the technologies employed. In this review, we will describe these modalities and provide a perspective on needed improvements that should render them more successful.

Antineoplastic Agents↗
PubMedDate not supplied

Microencapsulation of low molecular weight heparin into polymeric particles designed with biodegradable and nonbiodegradable polycationic polymers.

Owing to its lack of oral absorption, heparin has to be administered parenterally. However, parental administration has negative aspects such as multiple injections, possible infection, patient inconvenience, and high cost. Now, low molecular weight heparin (LMWH) is taking part in antithrombotic treatment and is proven to confer more advantages than unfractionated heparin. The aim of our present study was to formulate, by the w/o/w emulsification process, LMWH microparticles as potential oral carriers prepared with biodegradable (poly-epsilon-caprolactone and poly-lactic-co-glycolic acid) and nonbiodegradable polycationic polymers (Eudragit RS and RL), used alone or blended. The encapsulation efficiency ranged from 16 to 47% and was highly dependent on the presence of the positively charged polymers. In the same way, a low in vitro LMWH release was observed when Eudragit polymers composed totally or partially the polymeric matrix, compared with biodegradable polymers exhibiting higher LMWH release (40 and 60%). For each formulation, LMWH released from microparticles preserved its biological activity as shown by the antifactor Xa activity. Experiments performed with fluorescein-labeled LMWH showed the drug distribution in microparticles and may give information about the mechanisms controlling LMWH encapsulation and release.

Drug Compounding↗
PubMed2006

Poly-alpha,beta-(N-(2-hydroxyethyl)-L-aspartamide)-g-poly(1,3trimethylene carbonate) amphiphilic graft co-polymer as a potential drug carrier.

A biodegradable amphiphilic graft polymer was successfully synthesized by grafting hydrophobic poly(1,3-trimethylene carbonate) (PTMC) sequences onto a hydrophilic poly-alpha,beta-(N-(2-hydroxyethyl)-L-aspartamide) (PHEA) backbone. The graft polymer, PHEA-g-PTMC, was synthesized by ring-opening polymerization initiated by the macroinitiator PHEA bearing hydroxyl groups without adding any catalyst. The graft polymer was characterized by Fourier transform infrared spectroscopy, 1H-nuclear magnetic resonance spectroscopy, combined size-exclusion chromatography and multiangle laser light scattering analysis. Two drugs with distinct water solubility, prednisone acetate and tegafur, were encapsulated in the PHEA-g-PTMC nanoparticles. The in vitro release of two drugs from PHEA-g-PTMC nanoparticle drug-delivery systems was investigated.

Biocompatible Materials↗
PubMedDate not supplied

Manufacturing techniques of biodegradable implants intended for intraocular application.

Polylactic acid and polylactic-co-glycolic acid are biocompatible and biodegradable polymers with wide utility for the design of controlled release systems for drugs. Regarding intraocular application, polymeric sustained-drug release systems are being studied to treat vitreoretinal diseases. Our work aimed to compare the influence of two implant manufacturing techniques, compression and hot molding, on the in vitro degradation of the polymeric matrices and on the release of dexamethasone acetate. The results showed that the manufacturing technique highly influences degradation and drug release processes. The compressed systems degraded faster and allowed one faster release of the drug.

Absorbable Implants↗
PubMedDate not supplied

Biodegradable PLGA microcarriers for injectable delivery of chondrocytes: effect of surface modification on cell attachment and function.

Poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres were prepared by an oil/water emulsion solvent evaporation method to use as an injectable microcarrier for cell delivery. Three different kinds of PLGA microspheres having hydrophobic, negatively charged, and positively charged surfaces were prepared. Hydrophobic and negatively charged PLGA microspheres were prepared by using terminally capped and uncapped PLGA polymer, respectively. Positively charged PLGA microspheres were prepared by blending PLGA with PLGA-g-poly(L-lysine) graft copolymer as a surface modifying agent. Bovine chondrocytes were cultured on the three PLGA microspheres under serum conditions to comparatively evaluate cell attachment, cell proliferation, and cell function with respect to surface properties. Positively charged PLGA microspheres showed the highest cell attachment, growth, and function compared to hydrophobic and negatively charged microspheres. Surface-modified PLGA microspheres can potentially be used as an injectable delivery system for cells into a tissue defect site.

Absorbable Implants↗
PubMed2002

Biodegradable poly (DL-lactide glycolide) microparticles as a vehicle for allergen-specific vaccines: a study performed with Ole e 1, the main allergen of olive pollen.

Ole e 1, the main allergen of the olive pollen, was entrapped in poly (DL-lactide glycolide) microparticles by a solvent evaporation double emulsion technique. The physical properties of the microparticles, such as particle size, surface morphology, allergen entrapment rate and antigen release pattern were investigated. Microparticles with a spherical morphology displayed a size range of less than 2 microm in diameter and antigen loading up to 60-70% (w/w). SDS-PAGE and immunoblotting of the released Ole e 1 confirmed that the molecular integrity and the antigenic properties of Ole e 1 remained unaltered by the encapsulation process or polymer degradation. This finding suggests that microparticles displaying small particle sizes, rapid antigen release and a high allergen/polymer ratio may be a suitable delivery system for antigen in hyposensitization therapy against allergy.

Allergens↗
PubMed2002

Poly(glutamic acid) poly(ethylene glycol) hydrogels prepared by photoinduced polymerization: Synthesis, characterization, and preliminary release studies of protein drugs.

A class of new biodegradable hydrogels based on poly(ethylene glycol) methacrylate-graft-poly(glutamic acid) and poly(ethylene glycol) dimethacrylate was synthesized by photoinduced polymerization. Because all the polymeric constituents were highly hydrophilic, crosslinking could be performed in aqueous solutions. This type of crosslinked hydrogel was prepared by modifying a select number of acidic side-groups on poly(glutamic acid) with poly(ethylene glycol) methacrylate. These modified chains were then crosslinked in the presence of poly(ethylene glycol) dimethacrylate under a photoinduced polymerization at a wavelength of 365 nm. Swelling experiments were conducted to study the crosslinking density, pH-responsive behavior, and degradation of the hydrogel. Results showed that the degree of swelling of this type of hydrogels increased as the crosslinker concentration (or density) was reduced. Because of the presence of acidic side chains on poly(glutamic acid), swelling behavior was found to be pH-responsive, increasing at high pH in response to the increase in the amount of ionized acidic side chains. The degradation rate of these hydrogels also varied with pH. More rapid degradation was observed under stronger alkaline conditions because of the hydrolysis of the ester bonds between the crosslinker and the polymer backbone. Practically useful degradation rates could be achieved for such hydrogels under physiological conditions. Drug release rates from these hydrogels were found to be proportional to the protein molecular weight and the crosslinker density; increasing at lower protein molecular weight or crosslinker density. The preliminary findings presented in this article suggest that this class of biodegradable hydrogels could be an attractive avenue for drug delivery applications. The specific photoinduced crosslinking chemistry used would permit hydrogels to be synthesized in existence of the entrapped macromolecular drugs including peptides, proteins, and cells. In addition, the rapid feature of this polymerization procedure along with the ability to perform hydrogel synthesis and drug loading in an aqueous environment would offer great advantages in retaining drug activity during hydrogel synthesis.

Biocompatible Materials↗
PubMed1998

Encapsulation of proteins for improved delivery.

Two recent advances have enabled the development of clinically useful, injectable, sustained-release protein formulations. The first is a nonaqueous, cryogenic atomization process that encapsulates the protein into microspheres composed of a biodegradable polymer from which the protein is released slowly. The second consists of numerous ways of maintaining protein stability within the microspheres for extended periods after injection. In addition to allowing less frequent administration of protein drugs, at possibly lower overall doses, it is possible that sustained-release formulations will justify commercial development of proteins that could not be marketed as solution formulations.

Delayed-Action Preparations↗
PubMed2001

Peptide vaccines and peptide libraries.

Synthetic immunogens, containing built-in adjuvanticity, B cell, T helper cell and CTL epitopes or mimotopes, are ideal and invaluable tools to study the immune response with respect to antigen processing and presentation. This serves as a basis for the development of complete and minimal vaccines which do not need large carrier proteins, further adjuvants, liposome formulations or other delivery systems. Combinatorial peptide libraries, either completely random or characterized by one or several defined positions, are useful tools for the identification of the critical features of B cell epitopes and of MHC class I and class II binding natural and synthetic epitopes. The complete activity pattern of an O/Xn library with hundreds of peptide collections, each made up from billions of different peptides, represents the ranking of amino acid residues mediating contact to the target proteins of the immune system. Combinatorial libraries support the design of peptides applicable in vaccination against infectious agents as well as therapeutic tumour vaccines. Using the principle of lipopeptide vaccines, strong humoral and cellular immune responses could be elicited. The lipopeptide vaccines are heat-stable, non-toxic, fully biodegradable and can be prepared on the basis of minimized epitopes by modern methods of multiple peptide synthesis. The lipopeptides activate the antigen-presenting macrophages and B cells and have been recently shown to stimulate innate immunity by specific interaction with receptors of the Toll family.

Animals↗
PubMed2005

Thioflavins released from nanoparticles target fibrillar amyloid beta in the hippocampus of APP/PS1 transgenic mice.

For the delivery of drugs into the brain, the use of nanoparticles as carriers has been described as a promising approach. Here, we prepared nanoparticles as carriers for the model drugs thioflavin T and thioflavin S that bind fibrillar amyloid beta peptides (Abeta). These polymer colloids are composed of a polystyrene core and a degradable PBCA [poly(butyl-2-cyanoacrylate)] shell with a diameter of 90-100nm as shown by dynamic light scattering. Fluorescence spectrophotometric analysis revealed that encapsulated thioflavin T exhibited significantly stronger fluorescence than the free fluorophore. The enzymatic degradation of core-shell nanoparticles, as required in vivo, was shown after their treatment with porcine liver esterase, a non-specific esterase, in vitro. Shells of nanoparticles were dose-dependently degraded while their polystyrene cores remained intact. In the cortices of 7-14 months old APP/PS1 mice with age-dependent beta-amyloidosis, thioflavins selectively targeted fibrillar Abeta after biodegradation-induced release from their nanoparticulate carriers upon intracerebral injection. Collectively, our data suggest that core-shell nanoparticles with controlled degradation in vivo can become versatile tools to trace and clear Abeta in the brain.

Alzheimer Disease↗
PubMed1997

The GyneFix implant systems for interval, postabortal and postpartum contraception: a significant advance in long-term reversible contraception. International Study Group on Intrauterine Drug Delivery.

Intrauterine contraception has a number of important advantages over other forms of contraception and remains, therefore, an important method of birth control. However, side-effects and other drawbacks have reduced its overall acceptance. Also misconceptions and lack of updated scientific knowledge among the potential users and providers are major obstacles to the widespread use of intrauterine contraception. Ideally, an intrauterine device (IUD) should prevent pregnancy effectively, be well tolerated, not become displaced or expelled over time, cause a minimum of side-effects, be long-lasting, have a strictly local effect, and be easy to insert and remove. A group at the University of Ghent, Belgium, the International Study Group on Intrauterine Drug Delivery, has developed, since 1985, a totally new concept in order to improve current intrauterine contraceptive efficacy and enhance tolerance, by creating a harmonious relationship between the uterine cavity and the contraceptive 'foreign body'. The new concept (GyneFix) consists of a non-biodegradable suture thread made of surgical 00 monofilament polypropylene on which six copper tubes are threaded, providing a total surface area of 330 mm2. The upper and lower tubes are crimped onto the thread to keep the tubes in place. The upper extremity of the thread is provided with a knot which serves as an anchor. The knot is implanted in the myometrium of the uterine fundus with a specially designed insertion instrument, thereby permanently securing the device in the uterine cavity. Since the initial clinical investigations, over 10,000 woman years of experience and up to 10 years' follow-up in international multicenter, non-comparative and comparative clinical trials have been collected. The clinical material also included a large number of nulligravid and nulliparous women. Due to the design characteristics of the GyneFix and its anchoring in the uterine fundus, an optimal tolerance and almost complete absence of expulsion were obtained. The constant release of copper ions in the upper part of the uterine cavity results in the high effectiveness of the anchored device. The effectiveness is higher than in the high-load conventional copper IUDs which have a risk of becoming displaced, partially or totally expelled in 10% or more (nulliparous women), resulting in a significant number of accidental pregnancies. The absence of frame and, as a consequence, its flexibility, explain the low incidence of side-effects and the very low incidence of complications, such as pelvic inflammatory disease and ectopic pregnancies. This new concept could be a major step forward in the acceptance of intrauterine contraception worldwide and increase its popularity. This article reviews the experience with the new concept for interval, postabortal and postpartum contraception.

Abortion, Induced↗