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Release Kinetics (release + kinetics)
Selected AbstractsRelease of gentamicin from bone regenerative materials: An in vitro studyJOURNAL OF BIOMEDICAL MATERIALS RESEARCH, Issue 1 2007M. Teller Abstract Antibiotic loading of bone regenerative materials is a promising way to protect augmentation procedures from infection during the resorption phase of bone substitutes. Especially in the early stage of implantation, it should protect the grafted site against microbiological pathogens. The present study reports the release kinetics of gentamicin after loading from two synthetic bone filling materials. The first, BONITmatrix®, is a biphasic calcium phosphate silica composite obtained by the sol,gel route consisting of 13% silicon dioxide (w/w) and calcium phosphates (hydroxyapatite/,-tricalcium phosphate 60/40 w/w). The second, Synthacer®, is a sintered hydroxyapatite ceramic. Gentamicin was loaded by dipping and by vacuum coating. Release kinetics of the loaded Gentamicin was investigated by fluorescence polarization immunoassay and by staphylococcus aureus assay. By dipping, loading failed for Synthacer, and it was 12.7 mg gentamicin per gram bone substitute for BONITmatrix. By vacuum coating, loading was 11.3 mg gentamicin per gram bone substitute for Synthacer and 7.4 mg gentamicin per gram bone substitute for BONITmatrix. Distinct release kinetics were measured. For Synthacer, a high initial release was followed by a lower protracted release level up to 28 days. For BONITmatrix release was continuous over the investigated 70-day period. The present data suggest that the porosity properties at the nano- and microscopic levels, or the composition are responsible for antibiotic loading and subsequent release. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006 [source] Simultaneous Immobilization of Bioactives During 3D Powder Printing of Bioceramic Drug-Release MatricesADVANCED FUNCTIONAL MATERIALS, Issue 10 2010Elke Vorndran Abstract The combination of a degradable bioceramic scaffold and a drug-delivery system in a single low temperature fabrication step is attractive for the reconstruction of bone defects. The production of calcium phosphate scaffolds by a multijet 3D printing system enables localized deposition of biologically active drugs and proteins with a spatial resolution of approximately 300,µm. In addition, homogeneous or localized polymer incorporation during printing with HPMC or chitosan hydrochloride allows the drug release kinetics to be retarded from first to zero order over a period of 3,4 days with release rates in the range 0.68%,0.96%,h,1. The reduction in biological activity of vancomycin, heparin, and rhBMP-2 following spraying through the ink jet nozzles is between 1% and 18%. For vancomycin, a further loss of biological activity following incorporation into a cement and subsequent in vitro release is 11%. While previously acknowledged as theoretically feasible, is its shown for the first time that bone grafts with simultaneous geometry, localized organic bioactive loading, and localized diffusion control are a physical reality. This breakthrough offers a new future for patients by providing the required material function to match patient bone health status, site of repair, and age. [source] Smart Hydrogels Co-switched by Hydrogen Bonds and ,,, Stacking for Continuously Regulated Controlled-Release SystemADVANCED FUNCTIONAL MATERIALS, Issue 4 2010Fang Li Abstract A series of hydrogels with continuously regulatable release behavior can be achieved by incorporating hydrogen bonding and ,,, stacking co-switches in polymers. A poly(nitrophenyl methacrylate- co -methacrylic acid) hydrogel (NPMAAHG) for control over drug release is fabricated by copolymerizing 4-nitrophenyl methacrylate and methacrylic acid using ethylene glycol dimethacrylate as a crosslinker. The carboxylic acid groups and nitrylphenyl groups form hydrogen bonds and ,,, stacking interactions, respectively, which act as switches to control the release of guest molecules from the polymers. As revealed by the simulated gastrointestinal tract drug release experiments, the as-synthesized NPMAAHG hydrogels can be regulated to release only 4.7% of drugs after 3,h in a simulated stomach and nearly 92.6% within 43,h in the whole digestive tract. The relation between the release kinetics and structures and the mechanism of the smart release control are analyzed in terms of diffusion exponent, swelling interface number, drug diffusion coefficient, and velocity of the swelling interface in detail. The results reveal that the release of guest molecules from the hydrogels can be continuously regulated for systemic administration by controlling the ratio of the hydrophilic hydrogen bonds and the hydrophobic ,,, stacking switches. [source] Self-Assembling Peptide as a Potential Carrier for Hydrophobic Anticancer Drug Ellipticine: Complexation, Release and In Vitro DeliveryADVANCED FUNCTIONAL MATERIALS, Issue 1 2009Shan Yu Fung Abstract The self-assembling peptide EAK16-II is capable of stabilizing hydrophobic compounds to form microcrystal suspensions in aqueous solution. Here, the ability of this peptide to stabilize the hydrophobic anticancer agent ellipticine is investigated. The formation of peptide-ellipticine suspensions is monitored with time until equilibrium is reached. The equilibration time is found to be dependent on the peptide concentration. When the peptide concentration is close to its critical aggregation concentration, the equilibration time is minimal at 5,h. With different combinations of EAK16-II and ellipticine concentrations, two molecular states (protonated or cyrstalline) of ellipticine could be stabilized. These different states of ellipticine significantly affect the release kinetics of ellipticine from the peptide-ellipticine complex into the egg phosphatidylcholine vesicles, which are used to mimic cell membranes. The transfer rate of protonated ellipticine from the complex to the vesicles is much faster than that of crystalline ellipticine. This observation may also be related to the size of the resulting complexes as revealed from the scanning electron micrographs. In addition, the complexes with protonated ellipticine are found to have a better anticancer activity against two cancer cell lines, A549 and MCF-7. This work forms the basis for studies of the peptide-ellipticine suspensions in vitro and in vivo leading to future development of self-assembling peptide-based delivery of hydrophobic anticancer drugs. [source] Antibacterial polyvinyl chloride/antibiotic films: The effect of solvent on morphology, antibacterial activity, and release kineticsJOURNAL OF APPLIED POLYMER SCIENCE, Issue 4 2010Martha Merchan Abstract Medical-grade polyvinyl chloride was modified with sodium ampicillin in a concentration range from 0 to 5 wt % by solvent casting technique using cyclohexanone and N,N -dimethylformamide. The obtained polymeric systems were characterized by optical microscopy, tensile test, and scanning electron microscopy. In addition, in vitro antibacterial activity against Gram-negative and Gram-positive bacteria was determined by an agar diffusion test. Antibiotic release experiments were performed in distilled water and physiological saline solution, which were monitored by UV-vis spectroscopy. The results showed a crucial role of the solvent on the morphology, antibacterial activity, and releasing characteristic of the ampicillin. Furthermore, a mathematical model was applied to data obtained from release study, to characterize the release kinetics of the ampicillin from the polyvinyl chloride-antibiotic systems. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010 [source] Evaluation of the potential of polymeric carriers based on chitosan- grafted -polyacrylonitrile in the formulation of drug delivery systemsJOURNAL OF APPLIED POLYMER SCIENCE, Issue 3 2010A. A. Sarhan Abstract Graft copolymerization of chitosan with acrylonitrile (AN) was carried out by free radical polymerization using KMnO4 and oxalic acid as a combined redox initiator system. Graft copolymerization was confirmed by Fourier transform infrared spectra (FTIR), proton nuclear magnetic resonance spectra (1H-NMR), thermal gravimetric analysis (TGA) measurements, and wide angle X-ray diffraction (WAXD). In addition, further modification of the cyano groups of the grafted copolymers was performed by partial hydrolysis into carboxylic function groups with various extents. The extent of hydrolysis was monitored using FTIR spectroscopy. The potential of the hydrolyzed and unhydrolyzed grafted copolymers as polymeric carriers for drug delivery systems was extensively studied by preparation of tablets incorporated with methyl orange (MO) as a drug model. In vitro drug release was carried out in simulated gastric and intestinal conditions. The effects of grafting percentage (GP) and the extent of hydrolysis on the release kinetics were evaluated. Release continued up to 24 h for both hydrolyzed and unhydrolysed chitosan- g -PAN copolymers. The nature of drug transport through the polymer matrices was studied by comparing with power law or Kormeyer-Peppas equation. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010 [source] Encapsulation efficiency and release behaviors of bovine serum albumin loaded in alginate microspheres prepared by sprayingJOURNAL OF APPLIED POLYMER SCIENCE, Issue 4 2008Jie Zhang Abstract Spraying and spraying with an electrostatic field (SEF) were employed to prepare alginate microspheres for delivering proteins, especially for intestinal digestive enzymes and cytokines. The encapsulation efficiency (EE) of a model protein [bovine serum albumin (BSA)] at a pH value lower than the isoelectric point was 20% higher than that at a natural pH. Moreover, for the microspheres prepared by SEF, EE improved significantly with increasing electric voltage. The interactions between BSA and the alginate microspheres were identified with Fourier transform infrared spectroscopy. The release profiles in vitro showed a controlled and pH-responsive release manner for the encapsulated BSA. A first-order release equation was postulated and modified to describe the release kinetics with an obviously initial burst release related to the eroded porous matrix. The equation fit the release data well when the pH value and composition of the release media were changed. The analysis of the release kinetics indicated that the drug release rate was in an inverse ratio to the diameter of the microspheres. Increasing the gas flow rate or electric voltage decreased both the mean diameter and size distribution of the microspheres significantly and enhanced the release rate of loaded drugs from alginate microspheres. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis analysis revealed that BSA kept its structural integrity during the encapsulation and release process. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008 [source] Modeling solvent evaporation during the manufacture of controlled drug-release coatings and the impact on release kinetics,,JOURNAL OF BIOMEDICAL MATERIALS RESEARCH, Issue 2 2009Chang-Soo Kim Abstract To improve functionality and performance, controlled drug-release coatings comprised of drug and polymer are integrated with traditional medical devices, e.g., drug eluting stents. Depending on manufacturing conditions, these coatings can exhibit complex microstructures. Previously, a thermodynamically consistent model was developed for microstructure evolution in these systems to establish relationships between process variables, microstructure, and the subsequent release kinetics. Calculations based on the model were, in general, consistent with experimental findings. However, because of assumptions regarding the evaporation of solvent during fabrication, the model was unable to capture variations through the coating thickness that are observed experimentally. Here, a straightforward method is introduced to incorporate solvent evaporation explicitly into the model. Calculations are used to probe the impact of solvent evaporation rate and drug loading on the microstructure that forms during manufacturing and subsequent drug release kinetics. The predicted structures and release kinetics are found to be consistent with experimental observations. Further, the calculations demonstrate that solvent evaporation rate can be as critical to device performance as the amount of drug within the coating. For example, changes of a factor of five in the amount of drug released were observed by modifying the rate of solvent evaporation during manufacturing. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009 [source] Release of gentamicin from bone regenerative materials: An in vitro studyJOURNAL OF BIOMEDICAL MATERIALS RESEARCH, Issue 1 2007M. Teller Abstract Antibiotic loading of bone regenerative materials is a promising way to protect augmentation procedures from infection during the resorption phase of bone substitutes. Especially in the early stage of implantation, it should protect the grafted site against microbiological pathogens. The present study reports the release kinetics of gentamicin after loading from two synthetic bone filling materials. The first, BONITmatrix®, is a biphasic calcium phosphate silica composite obtained by the sol,gel route consisting of 13% silicon dioxide (w/w) and calcium phosphates (hydroxyapatite/,-tricalcium phosphate 60/40 w/w). The second, Synthacer®, is a sintered hydroxyapatite ceramic. Gentamicin was loaded by dipping and by vacuum coating. Release kinetics of the loaded Gentamicin was investigated by fluorescence polarization immunoassay and by staphylococcus aureus assay. By dipping, loading failed for Synthacer, and it was 12.7 mg gentamicin per gram bone substitute for BONITmatrix. By vacuum coating, loading was 11.3 mg gentamicin per gram bone substitute for Synthacer and 7.4 mg gentamicin per gram bone substitute for BONITmatrix. Distinct release kinetics were measured. For Synthacer, a high initial release was followed by a lower protracted release level up to 28 days. For BONITmatrix release was continuous over the investigated 70-day period. The present data suggest that the porosity properties at the nano- and microscopic levels, or the composition are responsible for antibiotic loading and subsequent release. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006 [source] Spatiotemporal Delivery Strategies for Promoting Musculoskeletal Tissue Regeneration,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2009Robert E Guldberg PhD Abstract A primary regenerative medicine strategy is to stimulate or augment endogenous repair mechanisms that promote functional restoration of damaged or degenerated tissues. There is increasing evidence that maximizing the potency of tissue regenerative therapies will require design and development of delivery approaches that provide controlled spatiotemporal release of key signaling molecules. Guidance on which factors to deliver and the timing of delivery is emerging from advances in understanding of critical pathways involved in the development of integrated musculoskeletal tissues. A broad range of biomaterials-based deployment technologies are becoming available that allow controlled spatial presentation and release kinetics of biological cues. The purpose of this perspective article is to review promising spatiotemporal delivery strategies designed to promote functional tissue regeneration with an emphasis on vascularized bone repair. [source] Lipophilic cationic drugs increase the permeability of lysosomal membranes in a cell culture system,JOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2010Johannes Kornhuber Lysosomes accumulate many drugs several fold higher compared to their extracellular concentration. This mechanism is believed to be responsible for many pharmacological effects. So far, uptake and release kinetics are largely unknown and interactions between concomitantly administered drugs often provoke mutual interference. In this study, we addressed these questions in a cell culture model. The molecular mechanism for lysosomal uptake kinetics was analyzed by live cell fluorescence microscopy in SY5Y cells using four drugs (amantadine, amitriptyline, cinnarizine, flavoxate) with different physicochemical properties. Drugs with higher lipophilicity accumulated more extensively within lysosomes, whereas a higher pKa value was associated with a more rapid uptake. The drug-induced displacement of LysoTracker was neither caused by elevation of intra-lysosomal pH, nor by increased lysosomal volume. We extended our previously developed numerical single cell model by introducing a dynamic feedback mechanism. The empirical data were in good agreement with the results obtained from the numerical model. The experimental data and results from the numerical model lead to the conclusion that intra-lysosomal accumulation of lipophilic xenobiotics enhances lysosomal membrane permeability. Manipulation of lysosomal membrane permeability might be useful to overcome, for example, multi-drug resistance by altering subcellular drug distribution. J. Cell. Physiol. 224:152,164, 2010 © 2010 Wiley-Liss, Inc. [source] Controlled drug delivery: therapeutic and pharmacological aspectsJOURNAL OF INTERNAL MEDICINE, Issue 5 2000J. Urquhart Abstract. Urquhart J (Department of Epidemiology, Pharmaco-epidemiology Group, Maastricht University, Maastricht, the Netherlands). Controlled drug delivery: therapeutic and pharmacological aspects (Internal Medicine in the 21st Century). J Intern Med 2000; 248: 357,376. Concerted work to develop human pharmaceuticals based on rate-controlled drug delivery systems began in 1970. Today there are over three dozen such products, plus a few for veterinary use. In addition, osmotic minipumps have been extensively used since 1978, resulting in over 6000 publications in the pharmacological, endocrinological and physiological literature. Rate-controlled delivery provides for drug entry into the bloodstream continuously at either a constant or a modulated rate. By this means, one avoids the usual peak and trough pattern of drug concentrations in plasma, with its echoing peak and trough pattern of drug actions, during the interval between successive doses. In contrast to the happenstance release kinetics of rapid-release dosage forms, rate-controlled delivery systems can be designed to provide specific temporal patterns of drug concentration in plasma, for the purpose of optimizing the selectivity of drug action, the interval between successive administerings of drug and the likelihood that the next administering will occur at the proper time. [source] Experimental and modeling analysis of diffusive release from single-shell microcapsulesAICHE JOURNAL, Issue 11 2009Enrique Muńoz Tavera Abstract There is much experimental and mathematical work that describes chemical transport from multilayered films of planar geometries. There is less so, however, for chemical transport from multilayered spheres, a common structure for controlled-release materials. Based on the Sturm,Liouville approach of Ramkrishna and Amundson (1974), explicit analytical solutions for the concentration profiles and release kinetics from spherical capsules are presented. Fluorescent dye-release studies using single-shelled microspheres called nanoparticle-assembled capsules were performed to validate the model for uniformly and nonuniformly sized capsules. The combined experiment-modeling approach allows optical microscopy images and release measurements to be readily analyzed for estimating diffusion coefficients in capsule core and shell walls. © 2009 American Institute of Chemical Engineers AIChE J, 2009 [source] Three-photon microscopy shows that somatic release can be a quantitatively significant component of serotonergic neurotransmission in the mammalian brainJOURNAL OF NEUROSCIENCE RESEARCH, Issue 15 2008S.K. Kaushalya Abstract Recent experiments on monoaminergic neurons have shown that neurotransmission can originate from somatic release. However, little is known about the quantity of monoamine available to be released through this extrasynaptic pathway or about the intracellular dynamics that mediate such release. Using three-photon microscopy, we directly imaged serotonin autofluorescence and investigated the total serotonin content, release competence, and release kinetics of somatic serotonergic vesicles in the dorsal raphe neurons of the rat. We found that the somata of primary cultured neurons contain a large number of serotonin-filled vesicles arranged in a perinuclear fashion. A similar distribution is also observed in fresh tissue slice preparations obtained from the rat dorsal raphe. We estimate that the soma of a cultured neuron on an average contains about 9 fmoles of serotonin in about 450 vesicles (or vesicle clusters) of ,370 nm average diameter. A substantial fraction (>30%) of this serotonin is released with a time scale of several minutes by K+ -induced depolarization or by para-chloroamphetamine treatment. The amount of releasable serotonin stored in the somatic vesicles is comparable to the total serotonin content of all the synaptic vesicles in a raphe neuron, indicating that somatic release can potentially play a major role in serotonergic neurotransmission in the mammalian brain. © 2008 Wiley-Liss, Inc. [source] Enhanced flexor tendon healing through controlled delivery of PDGF-BBJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 9 2009Stavros Thomopoulos Abstract A fibrin/heparin-based delivery system was used to provide controlled delivery of platelet derived growth factor BB (PDGF-BB) in an animal model of intrasynovial flexor tendon repair. We hypothesized that PDGF-BB, administered in this manner, would stimulate cell proliferation and matrix remodeling, leading to improvements in the sutured tendon's functional and structural properties. Fifty-six flexor digitorum profundus tendons were injured and repaired in 28 dogs. Three groups were compared: (1) controlled delivery of PDGF-BB using a fibrin/heparin-based delivery system; (2) delivery system carrier control; and (3) repair- only control. The operated forelimbs were treated with controlled passive motion rehabilitation. The animals were euthanized at 7, 14, and 42 days, at which time the tendons were assessed using histologic (hyaluronic acid content, cellularity, and inflammation), biochemical (total DNA and reducible collagen crosslink levels), and biomechanical (gliding and tensile properties) assays. We found that cell activity (as determined by total DNA, collagen crosslink analyses, and hyaluronic acid content) was accelerated due to PDGF-BB at 14 days. Proximal interphalangeal joint rotation and tendon excursion (i.e., tendon gliding properties) were significantly higher for the PDGF-BB-treated tendons compared to the repair-alone tendons at 42 days. Improvements in tensile properties were not achieved, possibly due to suboptimal release kinetics or other factors. In conclusion, PDGF-BB treatment consistently improved the functional but not the structural properties of sutured intrasynovial tendons through 42 days following repair. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res [source] Mechanistic understanding of degradation in bioerodible polymers for drug deliveryAICHE JOURNAL, Issue 12 2002Domenico Larobina A new model was developed to understand the mechanism of erosion in bioerodible polymers, which is essential to accurately predict drug release and precisely design controlled release devices. This model takes into account the phenomenon of microphase separation observed for polyanhydrides of certain copolymer compositions, and assumes that erosion is dominated by degradation and, thus, in a system with a fast eroding and a slow eroding species, two rate constants,one for each species,essentially control the evolution of the polymer microstructure. Expressions were derived for the fraction of each monomer released, as well as for the porosity in the system. A partition coefficient accounts for thermodynamic partitioning of a drug into the microdomains. The solutions of the model equations were fitted to experimental data on monomer release kinetics from two polyanhydride systems to obtain the erosion rate constants. Drug release kinetics experiments are compared to the model solution for drug release, and the partition coefficient of the drug is obtained from the fits. The comparisons to the data are promising, while pointing out the limitations of the model. The model does not account for oligomer formation prior to monomer release or for the dependence of the rate constants on parameters such as the degree of crystallinity, the local pH, and the polymer molecular weight. [source] Liposome transport of hydrophobic drugs: Gel phase lipid bilayer permeability and partitioning of the lactone form of a hydrophobic camptothecin, DB-67JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 1 2008Vijay Joguparthi Abstract The design of liposomal delivery systems for hydrophobic drug molecules having improved encapsulation efficiency and enhanced drug retention would be highly desirable. Unfortunately, the poor aqueous solubility and high membrane binding affinity of hydrophobic drugs necessitates extensive validation of experimental methods to determine both liposome loading and permeability and thus the development of a quantitative understanding of the factors governing the encapsulation and retention/release of such compounds has been slow. This report describes an efflux transport method using dynamic dialysis to study the liposomal membrane permeability of hydrophobic compounds. A mathematical model has been developed to calculate liposomal membrane permeability coefficients of hydrophobic compounds from dynamic dialysis experiments and partitioning experiments using equilibrium dialysis. Also reported is a simple method to study the release kinetics of liposome encapsulated camptothecin lactone in plasma by comparing the hydrolysis kinetics of liposome entrapped versus free drug. DB-67, a novel hydrophobic camptothecin analogue has been used as a model permeant to validate these methods. Theoretical estimates of DB-67 permeability obtained from the bulk solubility diffusion model and the "barrier-domain" solubility diffusion model are compared to the experimentally observed value. The use of dynamic dialysis in drug release studies of liposome and other nanoparticle formulations is further discussed and experimental artifacts that can arise without adequate validation are illustrated through simulations. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:400,420, 2008 [source] Drug release properties of polymer coated ion-exchange resin complexes: Experimental and theoretical evaluationJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 3 2007Seong Hoon Jeong Abstract Although ion-exchange resins have been used widely as drug delivery systems, their exact release kinetics has not been reported yet. Usually only the rate-limiting step has been taken into account and the rest of the steps have been ignored as instantaneous processes. To investigate the exact release kinetics of polymer-coated drug/ion-exchange resin complexes for sustained drug delivery, the results of new mathematical modeling were compared with experimental results. Drug/resin complexes with a model drug, dextromethorphan, were prepared and used as cores for fluid-bed coating. An aqueous colloidal dispersion of poly(vinyl acetate) was applied for the coating. A comprehensive mathematical model was developed using a mechanistic approach by considering diffusion, swelling, and ion-exchange processes solved by numerical techniques. The rate-limiting factor of the uncoated resin particles was diffusion through the core matrix. Similarly, in the coated particles the rate-limiting factor was diffusion through the coating membrane. The mathematical model has captured the phenomena observed during experimental evaluations and the release dynamics from uncoated and coated (at different coat levels) particles were predicted accurately (maximum RMSE 2.4%). The mathematical model is a useful tool to theoretically evaluate the drug release properties from coated ion-exchange complexes thus can be used for design purposes. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci [source] Acrylic polymers as thickening agents for tetraglycol cosolventJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 4 2006Giulia Bonacucina Abstract This article evaluated the thickening properties of two different Eudragits, L and RS, in tetraglycol cosolvent in order to obtain high viscosity systems characterized by controlled release properties. Tetraglycol was chosen for its ability to dissolve a wide range of water insoluble drugs, while Eudragit RS and L for their specific dissolution and permeability properties under physiological conditions. Study of the rheological properties was performed to characterize elastic and viscous properties of Eudragit/tetraglycol samples in function of frequency and temperature. For all systems, the results outlined a liquid like behavior, as observed for dilute polymer solutions. In fact the fitting of the log G,-log G,, versus frequency curves showed a good agreement with the Rouse or Zimm models. So despite the increase in viscosity, samples still behaved like liquid systems. After the addition of paracetamol the release characteristics were defined pointing out the great release control properties of both Eudragit L and RS, which showed different release kinetics depending on the pH of the environment. Semisolid Eudragits/tetraglycol systems can be considered as a new alterative for the sustained release of insoluble or poorly water-soluble drugs. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95:726,736, 2006 [source] Pharmaceutical and immunological evaluation of a single-shot hepatitis B vaccine formulated with PLGA microspheresJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 4 2002Li Shi Abstract A single-shot Hepatitis B vaccine formulation using poly(d,l)-lactide-co-glycolide acid (PLGA) microspheres as a delivery system was examined using a variety of biophysical and biochemical techniques as well as immunological evaluation in C3H mice. PLGA microsphere encapsulation of the Hepatitis B surface antigen (HBsAg), a lipoprotein particle, resulted in good recoveries of protein mass, protein particle conformational integrity, and in vitro antigenicity. Some partial delipidation of the HBsAg, however, was observed. The loading and encapsulation efficiency of HBsAg into the PLGA microspheres were measured along with the morphology and size distribution of the vaccine-loaded PLGA microspheres. The in vitro release kinetics of HBsAg from the PLGA microspheres was evaluated and found to be affected by experimental conditions such as stirring rate. HBsAg showed enhanced storage stability at 37°C in the slightly acidic pH range reported to be found inside PLGA microspheres; thus, the antigen is relatively stable under conditions of temperature and pH that may mimic in vivo conditions. The immunogenicity of the microsphere formulations of HBsAg was compared with conventional aluminum adjuvant formulated HBsAg vaccine in C3H mice. Comparisons were made between aluminum formulations (one and two injections), PLGA microsphere formulations (single injection), and a mixture of aluminum and PLGA microsphere formulations (single injection). The nine-month serum antibody titers indicate that a single injection of a mixture of aluminum and PLGA-formulated HBsAg results in equal or better immune responses than two injections of aluminum-formulated HBsAg vaccine. Based on these invitro and in vivo studies, it is concluded that HBsAg can be successfully encapsulated and recovered from the PLGA microspheres and a mixture of aluminum-adjuvanted and PLGA-formulated HBsAg can auto-boost an immune response in manner comparable to multiple injections of an aluminum-formulated vaccine. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:1019,1035, 2002 [source] Effect of surfactant on fabrication and characterization of paclitaxel-loaded polybutylcyanoacrylate nanoparticulate delivery systemsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 7 2003Amitava Mitra ABSTRACT The feasibility of applying biodegradable polybutylcyanoacrylate (PBCA) nanoparticulate delivery systems (NDSs) for the controlled release of paclitaxel was investigated. Paclitaxel-loaded and unloaded PBCA-NDSs containing various surfactants (dextran 70, cholesterol, polyvinyl alcohol and lecithin) were prepared by anionic polymerization. The effects of surfactant (1% w/v), surfactant combination (1% w/v each), and surfactant concentration (0.05, 1.0 and 2.5% w/v) on PBCA-NDSs were evaluated and characterized by particle size, zeta potential, entrapment efficiency, and in-vitro paclitaxel release kinetics. The physicochemical characteristics of PBCA-NDSs incorporated with various surfactants were significantly improved compared with PBCA-NDS without any surfactant, by decreasing particle size at least 3-fold as well as by increasing the zeta potential up to 18-fold to minimize the agglomeration of nanoparticles. Moreover, PBCA-NDSs incorporated with various surfactants demonstrated higher entrapment efficiency of paclitaxel. Results from the in-vitro release kinetic studies indicated that a more controlled biphasic zero-order release pattern of paclitaxel was observed for PBCA-NDSs incorporated with various surfactants. Compared with dextran 70 and polyvinyl alcohol, the naturally occurring lipids, lecithin and cholesterol, indicated greater advantages in improving the physicochemical properties of PBCA-NDSs, in terms of smaller particle size, higher zeta potential and better drug entrapment efficiency, and better controlled release of paclitaxel, in terms of lower release rate and prolonged action from PBCA-NDSs. [source] Dispersion polymerization of vinyl monomers in supercritical carbon dioxide in the presence of drug molecules: A one-pot route for the preparation of controlled delivery systemsJOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 22 2008Alessandro Galia Abstract The polymerization of 1-vinyl-2-pyrrolidone in supercritical carbon dioxide in the presence of ibuprofen as a model drug was investigated as a new one-pot process for the preparation of polymer-based drug delivery systems (DDSs). The composites were prepared at 65 °C and P = 31,42 MPa by changing the initial concentration of the drug and the concentration of a crosslinking agent and that of a hydrophobic comonomer. The effects of these parameters on the performances of the polymerization and on the in vitro release kinetics of ibuprofen were studied. In all the experiments, part of the drug was entrapped inside the polymer particles and dissolved more slowly with respect to the pure compound. Copolymerization with methyl methacrylate was the most effective route to obtain a DDS with sustained temporal release of the drug molecule. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 7429,7446, 2008 [source] Transformation of antimicrobial into bradykinin-potentiating peptides during peptic hydrolysis of bovine haemoglobin: identification, release kinetics and reaction network of peptidesJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 3 2007Wei Qi Abstract The precursor cleavage of the antimicrobial peptide ,107,136 into the bradykinin-potentiating peptide ,110,125 during peptic hydrolysis of bovine haemoglobin was investigated by reverse phase high-performance liquid chromatography coupled with tandem mass spectrometry. The optimal conditions for the preparation of ,107,136 and ,110,125 were found to be low and high degrees of hydrolysis respectively. A total of six peptides were identified as being involved in the cleavage process. Moreover, the reaction network of these peptides was developed according to the sequence alignment and their release kinetics. The affinity of pepsin towards different peptide bonds of bovine haemoglobin was also compared based on data from the release kinetics of peptides. In addition, some potentially bioactive peptides were predicted by means of sequence analysis and secondary structure calculations. Copyright © 2006 Society of Chemical Industry [source] Loading of Bacterial Cellulose Aerogels with Bioactive Compounds by Antisolvent Precipitation with Supercritical Carbon DioxideMACROMOLECULAR SYMPOSIA, Issue 2 2010Emmerich Haimer Abstract Bacterial cellulose aerogels overcome the drawback of shrinking during preparation by drying with supercritical CO2. Thus, the pore network of these gels is fully accessible. These materials can be fully rewetted to 100% of its initial water content, without collapsing of the structure due to surface tension of the rewetting solvent. This rehydration property and the high pore volume of these material rendered bacterial cellulose aerogels very interesting as controlled release matrices. Supercritical CO2 drying, the method of choice for aerogel preparation, can simultaneously be used to precipitate solutes within the cellulose matrix and thus to load bacterial cellulose aerogels with active substances. This process, frequently termed supercritical antisolvent precipitation, is able to perform production of the actual aerogel and its loading in one single preparation step. In this work, the loading of a bacterial cellulose aerogel matrix with two model substances, namely dexpanthenol and L-ascorbic acid, and the release behavior from the matrix were studied. A mathematical release model was applied to model the interactions between the solutes and the cellulose matrix. The bacterial cellulose aerogels were easily equipped with the reagents by supercritical antisolvent precipitation. Loading isotherms as well as release kinetics indicated no specific interaction between matrix and loaded substances. Hence, loading and release can be controlled and predicted just by varying the thickness of the gel and the solute concentration in the loading bath. [source] Localized delivery of growth factors for periodontal tissue regeneration: Role, strategies, and perspectives,MEDICINAL RESEARCH REVIEWS, Issue 3 2009Fa-Ming Chen Abstract Difficulties associated with achieving predictable periodontal regeneration, means that novel techniques need to be developed in order to regenerate the extensive soft and hard tissue destruction that results from periodontitis. Localized delivery of growth factors to the periodontium is an emerging and versatile therapeutic approach, with the potential to become a powerful tool in future regenerative periodontal therapy. Optimized delivery regimes and well-defined release kinetics appear to be logical prerequisites for safe and efficacious clinical application of growth factors and to avoid unwanted side effects and toxicity. While adequate concentrations of growth factor(s) need to be appropriately localized, delivery vehicles are also expected to possess properties such as protein protection, precision in controlled release, biocompatibility and biodegradability, self-regulated therapeutic activity, potential for multiple delivery, and good cell/tissue penetration. Here, current knowledge, recent advances, and future possibilities of growth factor delivery strategies are outlined for periodontal regeneration. First, the role of those growth factors that have been implicated in the periodontal healing/regeneration process, general requirements for their delivery, and the different material types available are described. A detailed discussion follows of current strategies for the selection of devices for localized growth factor delivery, with particular emphasis placed upon their advantages and disadvantages and future prospects for ongoing studies in reconstructing the tooth supporting apparatus. © 2009 Wiley Periodicals, Inc. Med Res Rev, 29, No. 3, 472-513, 2009 [source] Location-dependent controlled release kinetics of model hydrophobic compounds from mesoporous silicon/biopolymer composite fibersPHYSICA STATUS SOLIDI (A) APPLICATIONS AND MATERIALS SCIENCE, Issue 6 2009Dongmei Fan Abstract In this study, biodegradable mesoporous Si (BioSiliconTM) was loaded with cis-(2,2,-bipyridine) dichlororuthenium (II) (Ru complex) as a model hydrophobic compound. This ruthenium complex-loaded BioSiliconTM was either partially embedded on the surface of electrospun polycaprolactone (PCL) fibers or fully encapsulated within the fibers. To study release profiles in the above model delivery systems, porous Si/PCL constructs were soaked in DI water at 37 °C and the UV,Vis absorption spectrum of the supernatant was measured as a function of time. These results show that the Ru complex was released in a sustained manner over 7-day period. In addition, it is shown that the controlled-release of this complex depends on both the spatial location of the complex in the PCL fibrous scaffolds as well as the amount of Ru compound loaded in the mesoporous Si. (© 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Modulation of dynamic release of vitamin B2 from a model pH-sensitive terpolymeric hydrogel systemPOLYMER INTERNATIONAL, Issue 12 2004Dr SK Bajpai Abstract Terpolymeric devices consisting of acrylamide, methacrylamide and acrylic acid were synthesized and the release of the model drug riboflavin from these devices was studied at the physiological temperature 37°C. The gels exhibit a sharp pH-dependent release behavior. The devices released nearly 42.2 ± 2.6% drug at pH 1.0 while nearly 95.3 ± 3.2% drug was released at pH 7.4. With increasing concentration of cross-linker in the gel, the drug released was found to decrease. Moreover, with low content of cross-linker a nearly zero-order profile was obtained. The size of the cylindrical devices also affected the release kinetics and a linear dependency was observed between t1/2 (ie, the time required for 50 % release) and the square of the diameter, thus supporting the Tanaka,Fillmore theory. The molar ratio of acrylamide and methacrylamide also affected the dynamic release of riboflavin. It was found that variation in transit time could also affect the drug-releasing capacity of the devices. Finally, the average and ,late-time' diffusion coefficients for the gels having different initial loads were also evaluated. Copyright © 2004 Society of Chemical Industry [source] Amphiphilic polyelectrolyte for stabilization of multiple emulsions,POLYMER INTERNATIONAL, Issue 4 2003Fanny Michaut Abstract Multiple emulsions are complex thermodynamically unstable systems where both types of emulsion coexist. We investigated the stability behaviour of water-in-oil-in-water (W/O/W) emulsions formulated with a hydrophobically modified poly(sodium acrylate) emulsifier at the outer interface and a monomeric surfactant (span 80) at the inner interface. Their stability was tested through release kinetics of a marker (NaCl) initially encapsulated in the aqueous droplets, and by rheology. Slow release rates and remarkably long shelf-life were obtained compared to typical multiple emulsions stabilized by two commonly used surfactants (span 80 and tween 20). In addition, we prepared stable highly concentrated multiple emulsions. Their rheological behaviour indicated that the internal interface was essentially covered with span 80. Thus, transportation of the polymer across the oil phase is limited, which in turn explains, at least partially, the stability improvement in the presence of the polymeric emulsifier. Finally, the long lifetime of the emulsions allowed study by diffusing wave spectroscopy of the interactions between the droplets and the globule surface which are important for understanding the destruction mechanisms of multiple emulsions. © 2003 Society of Chemical Industry [source] The controlled release behavior and pH- and thermo-sensitivity of alginate/poly(vinyl alcohol) blended hydrogelsPOLYMERS FOR ADVANCED TECHNOLOGIES, Issue 8 2009Win-Chun Jao Abstract Poly(vinyl alcohol) (PVA) was blended with sodium alginate (Alg) in various ratios and crosslinked with calcium chloride and made into hydrogel membranes. The dependence of the swelling behavior of these Alg-Ca/PVA hydrogels on pH was investigated. The temperature-dependent swelling behavior of the semi-interpenetrating network (semi-IPN) hydrogels was examined at temperatures from 2 to 45°C and the enthalpy of mixing (,Hmix) was determined at various temperatures. The molecular structure of the hydrogels was studied by infrared spectroscopy and their water structure in the semi-IPN hydrogels was measured by differential scanning calorimetry (DSC). The influence of Ca2+ content on the network structure of Alg-Ca/PVA hydrogels was investigated in terms of the compressive elastic modulus, effective crosslinking density, and the polymer,solvent interaction parameter based on the Flory theory. The loading of alizarin red S (ARS) followed the Langmuir isotherm mechanism and the release kinetics of ARS from the Alg-Ca/PVA hydrogels followed the Fickian diffusion mechanism. Copyright © 2008 John Wiley & Sons, Ltd. [source] Relationship among drug delivery behavior, degradation behavior and morphology of copolylactones derived from glycolide, l -lactide and ,-caprolactonePOLYMERS FOR ADVANCED TECHNOLOGIES, Issue 2 2002Qing Cai Abstract A series of copolylactones was synthesized by ring-opening copolymerization of glycolide, L -lactide and ,-caprolactone, using stannous octoate as catalyst. The in vitro degradation behaviors of them were studied and data demonstrated different degradation rates which mainly depended on the compositions. Investigation of the 5-fluorouracil (5-Fu) release from these copolylactones revealed that the composition, degradation rate and the morphology of the polymeric matrix played an important role on the drug release kinetics. A sustained 5-Fu release without initial time lag was obtained from random poly(lactide-co-glycolide-co-caprolactone) (r-PGLC) drug carrier, and it differed from the cases of polylactide (PLA) or random poly(lactide-co-glycolide) (PLGA), which usually showed an initial time lag or biphasic drug release behavior. It was due to the low glass transition temperature (Tg) of the r-PGLC and the drug would diffuse faster in rubbery state under the experimental temperature. Furthermore, a significant change in the drug release behavior of r-PGLC was observed when the temperatures were changed around the Tg of the drug carrier, which implied that the drug release behavior could be regulated by adjusting the morphology of the drug carrier. Copyright © 2002 John Wiley & Sons, Ltd. [source] | |||||||||||||||||||