Burst Release (burst + release)

Distribution by Scientific Domains

Kinds of Burst Release

  • initial burst release

  • Selected Abstracts

    Effects of ethyl benzoate on performance, morphology, and erosion of PLGA implants formed in situ

    R. Astaneh
    Abstract An in situ forming implant (ISFI) is a novel drug delivery system used for protein and peptide delivery, especially for cancer treatment. An ISFI based on 33% (w/w) poly(D,L -lactide- co -glycolide)(PLGA; 50:50)/3% (w/w) leuprolide acetate (LA)/64% (w/w) N -methyl-2-pyrrolidone (NMP) was prepared for this study. After injection of the final formulation, which is a viscous liquid to an aqueous medium, it deforms to become a semisolid or solid matrix. The performance of this matrix was investigated on the basis of peptide release from it. Erosion and morphology of ISFI were also studied. The effects of adding 12.8% (w/w) ethyl benzoate (EB) as a rate-modifying agent on performance, erosion, and morphology of ISFI were assessed. The implant containing EB showed very low burst release (5.53% ± 0.82%) and the morphology turns to closed pore-like structures. After adding EB, the morphology turns to closed pore-like structures. This type of morphology has very close relation to the performance of the implant as well. Finally, the effect of EB on performance, erosion, and morphology is explained by means of solvent,nonsolvent affinity, water permeation, and the rate of phase inversion. © 2008 Wiley Periodicals, Inc. Adv Polym Techn 27:17,26, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/adv.20114 [source]

    In vitro release of complexed pDNA from biodegradable polymer films

    Y. Ramgopal
    Abstract The controlled delivery of low-molecular weight drugs and proteins from biodegradable polymers has received considerable attention. However, controlled release studies of pDNA from such polymers have not been reported to date. In this study, a plasmid DNA was complexed with the cationic polymer called polyethylenimine (PEI). This gene vector has been shown to be very effective in transfecting cells. The complexed DNA were then incorporated into different types of poly-lactic- co -glycolic acid (PLGA) film; PLGA 53/47 (Mw 90 kDa), 50/50 (Mw 11 kDa, end group is lauryl ester) and 75/25 (Mw 120 kDa). Their release profiles from a buffer solution were studied. An initial (small) burst release of PEI-DNA from film was observed in PLGA 53/47 and 50/50, followed by a plateau phase and finally a rapid erosion-controlled release. For PLGA 50/50, the rapid release started after 14 days; erosion-controlled release for PLGA 53/47 started after 9 days; for PLGA 75/25, the release rate was governed by an initial burst release (10%) followed by a slow release controlled by diffusion. No obvious erosion-controlled release rate was observed for this polymer up to 27 days. Thus, the controlled release of complexed DNA follows the general features exhibited by lower- Mw drugs. This is of significance in designing gene vector matrices that offer the promise of more lasting gene therapy compared with particulate formulations. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008 [source]

    Intermittent watt-level ultrasonication facilitates vancomycin release from therapeutic acrylic bone cement

    Xun-Zi Cai
    Abstract Ultrasound holds promise for enhancing the vancomycin release from cement though the length of time when local drug level exceeded the minimum inhibitory concentration (T>MIC) was not prolonged by the previous protocol of milliwatt-level ultrasonication. Here vancomycin-loaded cements were subjected to continuous watt-level ultrasonication (CUG), intermittent watt-level ultrasonication (IUG) or no ultrasonication (NUG) for 14 d during immersion in 40-ml phosphate buffered saline (PBS) for 28 d. The T>MIC for IUG was more than three times that for NUG. In contrast, T>MIC for CUG was slightly shortened. The subtherapeutic release of vancomycin between 15 d and 28 d for IUG was one-ninth that for NUG. The fitting equations indicated a significant enhancement on the burst release and the slow release for IUG; however, the continuous ultrasonication hampered the slow release. SEM images exhibited denser craters and pores with larger diameters and less residual drug in specimens from IUG relative to those from both CUG and NUG. Intermittent watt-level ultrasonication improved the ultrasound-enhanced vancomycin release from cement in view of the prolonged T>MIC and the inhibited subtherapeutic release compared with continuous ultrasonication. The mechanisms may be associated with the distinctive effects of detaching forces and pushing forces by acoustic microstreams. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009 [source]

    In vivo release of the antimicrobial peptide hLF1-11 from calcium phosphate cement,

    Hein P. Stallmann
    Abstract We studied the release of human lactoferrin 1-11 (hLF1-11), a potent antimicrobial peptide, in an animal model. Calcium phosphate cement with 50 mg/g hLF1-11 was injected into the femoral canal of 12 rabbits. One, 3, and 7 days later, four animals were terminated, and the femora excised. Sections of bone and cement were removed for histological analysis. We used liquid chromatography-mass spectrometry/mass spectrometry for semiquantitative determination of the hLF1-11 concentration. Blood samples were drawn for leukocyte count and differentiation to identify a potential immunomodulating effect of hLF1-11. After an initial burst release, the hLF1-11 concentration in cement and bone decreased steadily. This in vivo release profile is consistent with earlier in vitro studies. Tissue ingrowth into the cement, without signs of inflammation or necrosis, was observed. Leukocytosis or a shift in leukocyte differentiation did not occur. The carrier released over 99% of the hLF1-11, resulting in peak concentrations at the cement,bone interface. This indicates that hLF1-11 could become a valuable prophylactic agent in osteomyelitis treatment. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:531,538, 2008 [source]

    Design and evaluation of a dry coated drug delivery system with floating,pulsatile release

    Hao Zou
    Abstract The objective of this work was to develop and evaluate a floating,pulsatile drug delivery system intended for chronopharmacotherapy. Floating,pulsatile concept was applied to increase the gastric residence of the dosage form having lag phase followed by a burst release. To overcome limitations of various approaches for imparting buoyancy, we generated the system which consisted of three different parts, a core tablet, containing the active ingredient, an erodible outer shell and a top cover buoyant layer. The dry coated tablet consists in a drug-containing core, coated by a hydrophilic erodible polymer which is responsible for a lag phase in the onset of pulsatile release. The buoyant layer, prepared with Methocel® K4M, Carbopol® 934P and sodium bicarbonate, provides buoyancy to increase the retention of the oral dosage form in the stomach. The effect of the hydrophilic erodible polymer characteristics on the lag time and drug release was investigated. Developed formulations were evaluated for their buoyancy, dissolution and pharmacokinetic, as well gamma-scintigraphically. The results showed that a certain lag time before the drug released generally due to the erosion of the dry coated layer. Floating time was controlled by the quantity and composition of the buoyant layer. Both pharmacokinetic and gamma-scintigraphic data point out the capability of the system of prolonged residence of the tablets in the stomach and releasing drugs after a programmed lag time. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:263,273, 2008 [source]

    Oral peptide delivery: in-vitro evaluation of thiolated alginate/poly(acrylic acid) microparticles

    Alexander Greimel
    ABSTRACT The purpose of this study was to develop an oral thiomer-based microparticulate delivery system for insulin by ionic gelation. The microparticulate matrix consisted of either poly(acrylic acid)-cysteine (PAA-Cys) and alginate-cysteine (Alg-Cys) or the corresponding unmodified polymers (PAA, Alg). Two different viscosities of alginates were provided for the study, low and medium. Three different types of microparticles were prepared via ionic gelation with calcium (Alg, AlgPAA and AlgPAA-Cys) and their different properties evaluated in-vitro (particle size and shape, drug loading and release profile, swelling and stability). The mean particle size of all formulations ranged from 400 to 600 ,m, revealing the lowest for thiolated microparticles. SEM micrographs showed different morphological profiles for the three different types of microparticles. Encapsulation efficiency of insulin increased within the following rank order: Alg (15%) < AlgPAA (40%) < AlgPAA-Cys (65%). Alginate and AlgPAA microparticles displayed a burst release after 30 min, whereas the thiolated particles achieved a controlled release of insulin over 3 h. The swelling ratio was pH dependent: in simulated intestinal fluid microparticles exhibited a much higher water uptake compared with simulated gastric fluid. Due to the formation of intraparticulate disulfide bonds during the preparation process, thiolated particles revealed a higher stability. It was also observed that the viscosity of the two alginates used had no influence on the properties of the particles. According to these results AlgPAA-Cys microparticles obtained by ionic gelation and stabilized via disulfide bonds might be an alternative tool for the oral administration of therapeutic peptides. [source]

    Self-Assembled Nanogel of Hydrophobized Dendritic Dextrin for Protein Delivery

    Yayoi Ozawa
    Abstract Highly branched cyclic dextrin derivatives (CH-CDex) that are partly substituted with cholesterol groups have been synthesized. The CH-CDex forms monodisperse and stable nanogels with a hydrodynamic radii of ,10 nm by the self-assembly of 4,6 CH-CDex macromolecules in water. The CH-CDex nanogels spontaneously trap 10,16 molecules of fluorescein isothiocyanate-labeled insulin (FITC-Ins). The complex shows high colloidal stability: no dissociation of trapped insulin is observed after at least 1 month in phosphate buffer (0.1 M, pH 8.0). In the presence of bovine serum albumin (BSA, 50 mg,·,mL,1), which is a model blood system, the FITC-Ins trapped in the nanogels is continuously released (,20% at 12 h) without burst release. The high-density nanogel structure derived from the highly branched CDex significantly affects the stability of the nanogel,protein complex. [source]

    Reduction-Sensitive Self-Aggregates as a Novel Delivery System

    Ju Eun Kim
    Abstract Methoxy PEG amine with molecular weight of 5k and , -caprolactone with molecular weight of 1,960 were conjugated to a peptide comprising three cysteine residues. The shift of peak molecular weight and narrow molecular weight distribution in GPC trace without any noticeable shoulder as well as 1H NMR analysis confirmed the successful synthesis of the copolymer. A modified O/W dialysis system was employed to prepare self-aggregates having the size around 210,nm. During the dialysis, stabilized aggregates were obtained by intermolecular disulfide bonds via oxidation. Critical aggregate concentration (CAC) of the copolymer was determined as 0.07,mg,·,mL,1 and disulfide-stabilized self-aggregates remained stable regardless of the concentration without displaying CAC. Doxorubicin-loading amount and efficiency was 8.7 and 26.0%, respectively. Release profile of doxorubicin below CAC at 37,°C showed a sustained release and the addition of D,L -dithiothreitol (DTT) after 24,h triggered a burst release of doxorubicin. Intermolecular disulfide bonds via oxidation stabilized the polymeric aggregates even in the diluted condition similar to that in the bloodstream and addition of DTT destabilized the aggregates to burst encapsulated doxorubicin in the reductive condition. [source]

    Liquid chromatography-tandem mass spectrometry method for determination of Sirolimus coated drug eluting nano porous carbon stents

    G. Rajender
    Abstract Liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has proved to powerful research tool due to its sensitivity, high selectivity, and high throughput efficiency..Sirolimus was extracted from plasma by two-step extraction procedure using chloroform as extracting solvent. Signal intensity was high using ESI+ source provided for the quantitation of samples. Chromatographic separation was performed on phenomenax C-18 column (250 × 4.60,mm 5microns).Mobile phase contains acetonitrile, water (80; 20 v/v) + 0.1% acetic acid, flow rate 1,mL/min. The retention time of Sirolimus 8.4,min, the total run time10,min. Linearity correlation coefficients (r2) curve was 0.997183.calibraction range 10,1000,ng/mL. The UV detection of Sirolimus was at 278(277.78) nm. Sirolimus coated drug eluting stents, MRM (Multiple reaction monitoring) transition of Sirolimus m/z 936.83,208.84 was selected to obtain maximum sensitivity. LC/MS/MS results exhibited consistency in drug content on the stent surface. In-vitro release kinetic indicated the release of Sirolimus in 41 days from the date of implanted. Drug release was found at the first day, burst release was observed at 7th day of implantation. This study involved pharmacological coating of stents, based on the notion that sustained systemic local delivery of anti-proliferative agents. LC-MS/MS method has been successfully used in the pharmacokinetic analysis of Sirolimus coated drug eluting stents. Copyright © 2009 John Wiley & Sons, Ltd. [source]

    A Novel Technique for Loading of Paclitaxel-PLGA Nanoparticles onto ePTFE Vascular Grafts

    Hyun Jung Lim
    The major cause of hemodialysis vascular access dysfunction (HVAD) is the occurrence of stenosis followed by thrombosis at venous anastomosis sites due to the aggressive development of venous neointimal hyperplasia. Local delivery of antiproliferative drugs may be effective in inhibiting hyperplasia without causing systemic side effects. We have previously demonstrated that paclitaxel-coated expanded poly(tetrafluoroethylene) (ePTFE) grafts, by a dipping method, could prevent neointimal hyperplasia and stenosis of arteriovenous (AV) hemodialysis grafts, especially at the graft-venous anastomoses; however, large quntities of initial burst release have remained a problem. To achieve controlled drug release, paclitaxel (Ptx)-loaded poly(lactic- co -glycolic acid) (PLGA) nanoparticles (Ptx-PLGA-NPs) were prepared by the emulsion-solvent evaporation method and then transferred to the luminal surface and inner part of ePTFE vascular grafts through our micro tube pumping and spin penetration techniques. Scanning electron microscope (SEM) images of various stages of Ptx-PLGA-NPs unequivocally showed that micro tube pumping followed by spin penetration effectively transferred Ptx-PLGA-NPs to the inner part, as well as the luminal surface, of an ePTFE graft. In addition, the in vitro release profiles of paclitaxel demonstrated that this new system achieved controlled drug delivery with a reduced initial burst release. These results suggest that loading of Ptx-PLGA-NPs to the luminal surface and the inner part of an ePTFE graft is a promising strategy to ultimately inhibit the development of venous neointimal hyperplasia. [source]