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Sample records for affected drug release

  1. Setting accelerated dissolution test for PLGA microspheres containing peptide, investigation of critical parameters affecting drug release rate and mechanism.

    PubMed

    Tomic, I; Vidis-Millward, A; Mueller-Zsigmondy, M; Cardot, J-M

    2016-05-30

    The objective of this study was development of accelerated in vitro release method for peptide loaded PLGA microspheres using flow-through apparatus and assessment of the effect of dissolution parameters (pH, temperature, medium composition) on drug release rate and mechanism. Accelerated release conditions were set as pH 2 and 45°C, in phosphate buffer saline (PBS) 0.02M. When the pH was changed from 2 to 4, diffusion controlled phases (burst and lag) were not affected, while release rate during erosion phase decreased two-fold due to slower ester bonds hydrolyses. Decreasing temperature from 45°C to 40°C, release rate showed three-fold deceleration without significant change in release mechanism. Effect of medium composition on drug release was tested in PBS 0.01M (200 mOsm/kg) and PBS 0.01M with glucose (380 mOsm/kg). Buffer concentration significantly affected drug release rate and mechanism due to the change in osmotic pressure, while ionic strength did not have any effect on peptide release. Furthermore, dialysis sac and sample-and-separate techniques were used, in order to evaluate significance of dissolution technique choice on the release process. After fitting obtained data to different mathematical models, flow-through method was confirmed as the most appropriate for accelerated in vitro dissolution testing for a given formulation. PMID:27025293

  2. Glucose cryoprotectant affects glutathione-responsive antitumor drug release from polysaccharide nanoparticles.

    PubMed

    Curcio, Manuela; Blanco-Fernández, Bárbara; Costoya, Alejandro; Concheiro, Angel; Puoci, Francesco; Alvarez-Lorenzo, Carmen

    2015-06-01

    The aim of this work was to prepare polysaccharide-based nanoparticles (NPs) sensitive to glutathione (GSH), and to elucidate the effect of the concentration of glucose used as cryoprotectant during freeze-drying on the GSH-responsiveness. NPs were obtained via ionic interaction between negatively charged polysaccharides, chondroitin sulfate and dermatan sulfate, and the positively charged thiolated chitosan (CSSH), and crosslinking of CSSH before or after the nanoparticles formation with a disulfide-bond containing crosslinker, N,N'-bis(acryloyl)cystamine (BAC). NPs were freeze-dried with glucose at two different concentrations (0.5 and 5.0%w/w) and then characterized as methotrexate delivery systems, studying the effect of GSH concentration on drug release, efficacy against tumor cells and cellular internalization. Non-loaded NPs were highly compatible with murine fibroblasts and showed a suitable size for being used in anticancer therapy. When methotrexate-loaded NPs were freeze-dried with the highest glucose concentration, they lost their responsiveness to GSH concentration in vitro. Drug-loaded NPs were shown to inhibit the growth of tumor cells (HeLa and CHO-K1) with greater efficiency than free methotrexate, disregarding the concentration of glucose used for freeze-drying. Nevertheless, confocal microscopy studies revealed that cellular internalization of NPs freeze-dried with 5.0% glucose is more difficult than for NPs freeze-dried with lower glucose concentration. Thus, concentration of glucose cryoprotectant should be taken into account during development of NPs intended to release the drug as a function of GSH levels, due to the specific interactions of glucose with GSH. PMID:25917641

  3. What Affects Reintegration of Female Drug Users after Prison Release? Results of a European Follow-Up Study

    ERIC Educational Resources Information Center

    Zurhold, Heike; Moskalewicz, Jacek; Sanclemente, Cristina; Schmied, Gabriele; Shewan, David; Verthein, Uwe

    2011-01-01

    The main objective of this follow-up study is to explore factors influencing the success or failure of women in reintegrating after their release from prison. Female drug users in five European cities were tracked after being released from prison. Out of 234 female prisoners contacted in prisons, 59 were included in the follow-up study. Structured…

  4. Factors affecting gallbladder motility: drugs.

    PubMed

    Marzio, L

    2003-07-01

    Various drugs and medications that inhibit or stimulate gallbladder contraction and basal tone in humans are described. Active gallbladder contraction may be achieved using synthetic hormones such as cholecystokinin, caerulein and motilin, cholinomimetic drugs such as bethanecol, prostigmine, and erythromycin due to its motilin-like effect. Furthermore, cisapride and cholestyramine, may have some excitatory activity on the gallbladder muscle. Intravenous amino acids also induce gallbladder contraction through the release of cholecystokinin. Inhibition of gallbladder contraction induced by a meal, or reduction of the basal fasting tone may be achieved by using atropine and other cholinergics, and by inhibitory hormones such as somatostatin, the nitric acid releaser arginine, the calcium channel antagonist nifedipine, and progesterone. Other drugs such as trimebutine, loperamide and ondansetron may negatively affect gallbladder contraction. PMID:12974504

  5. Drugs affecting glycosaminoglycan metabolism.

    PubMed

    Ghiselli, Giancarlo; Maccarana, Marco

    2016-07-01

    Glycosaminoglycans (GAGs) are charged polysaccharides ubiquitously present at the cell surface and in the extracellular matrix. GAGs are crucial for cellular homeostasis, and their metabolism is altered during pathological processes. However, little consideration has been given to the regulation of the GAG milieu through pharmacological interventions. In this review, we provide a classification of small molecules affecting GAG metabolism based on their mechanism of action. Furthermore, we present evidence to show that clinically approved drugs affect GAG metabolism and that this could contribute to their therapeutic benefit. PMID:27217160

  6. Drugs affecting the eye.

    PubMed

    Taylor, F

    1985-08-01

    This discussion reviews drugs that affect the eye, including antihyperglycemic agents; corticosteroids; antirheumatic drugs (quinolines, indomethacin, and allopurinol); psychiatric drugs (phenothiazine, thioridazine, and chlorpromazine); drugs used in cardiology (practolol, amiodarone, and digitalis gylcosides); drugs implicated in optic neuritis and atrophy, drugs with an anticholinergic action; oral contraceptives (OCs); and topical drugs and systemic effects. Refractive changes, either myopic or hypermetropic, can occur as a result of hyperglycemia, and variation in vision is sometimes a presenting symptom in diabetes mellitus. If it causes a change in the refraction, treatment of hyperglycemia almost always produces a temporary hypermetropia. A return to the original refractive state often takes weeks, sometimes months. There is some evidence that patients adequately treated with insulin improve more rapidly than those taking oral medication. Such patients always should be referred for opthalmological evaluation as other factors might be responsible, but it might not be possible to order the appropriate spectacle correction for some time. The most important ocular side effect of the systemic adiministration of corticosteroids is the formation of a posterior subcapsular cataract. Glaucoma also can result from corticosteroids, most often when they are applied topically. Corticosteroids have been implicated in the production of benign intracranial hypertension, which is paradoxical because they also are used in its treatment. The most important side effect of drugs such as chloroquine and hydroxychloroquine is an almost always irreversible maculopathy with resultant loss of central vision. Corneal and retinal changes similar to those caused by the quinolines have been reported with indomethacin, but there is some question about a cause and effect relationship. The National Registry of Drug Induced Ocular Side Effects in the US published 30 case histories of

  7. Controlled Drug Release from Pharmaceutical Nanocarriers

    PubMed Central

    Lee, Jinhyun Hannah; Yeo, Yoon

    2014-01-01

    Nanocarriers providing spatiotemporal control of drug release contribute to reducing toxicity and improving therapeutic efficacy of a drug. On the other hand, nanocarriers face unique challenges in controlling drug release kinetics, due to the large surface area per volume ratio and the short diffusion distance. To develop nanocarriers with desirable release kinetics for target applications, it is important to understand the mechanisms by which a carrier retains and releases a drug, the effects of composition and morphology of the carrier on the drug release kinetics, and current techniques for preparation and modification of nanocarriers. This review provides an overview of drug release mechanisms and various nanocarriers with a specific emphasis on approaches to control the drug release kinetics. PMID:25684779

  8. Fabrication of drug eluting implants: study of drug release mechanism from titanium dioxide nanotubes

    NASA Astrophysics Data System (ADS)

    Hamlekhan, Azhang; Sinha-Ray, Suman; Takoudis, Christos; Mathew, Mathew T.; Sukotjo, Cortino; Yarin, Alexander L.; Shokuhfar, Tolou

    2015-06-01

    Formation of titanium dioxide nanotubes (TNTs) on a titanium surface holds great potential for promoting desirable cellular response. However, prolongation of drug release from these nano-reservoirs remains to be a challenge. In our previous work TNTs were successfully loaded with a drug. In this study the effect of TNTs dimensions on prolongation of drug release is quantified aiming at the introduction of a simple novel technique which overcomes complications of previously introduced methods. Different groups of TNTs with different lengths and diameters are fabricated. Samples are loaded with a model drug and rate of drug release over time is monitored. The relation of the drug release rate to the TNT dimensions (diameter, length, aspect ratio and volume) is established. The results show that an increase in any of these parameters increases the duration of the release process. However, the strongest parameter affecting the drug release is the aspect ratio. In fact, TNTs with higher aspect ratios release drug slower. It is revealed that drug release from TNT is a diffusion-limited process. Assuming that diffusion of drug in (Phosphate-Buffered Saline) PBS follows one-dimensional Fick’s law, the theoretical predictions for drug release profile is compatible with our experimental data for release from a single TNT.

  9. Factors affecting sporoplasm release in Kudoa septempunctata.

    PubMed

    Shin, Sang Phil; Zenke, Kosuke; Yokoyama, Hiroshi; Yoshinaga, Tomoyoshi

    2015-02-01

    The myxosporean parasite Kudoa septempunctata has been isolated from cultured olive flounder (Paralichthys olivaceus) and was recently identified as a cause of food poisoning in humans. Since the sporoplasm plays an important role in causing diarrhea by invading intestinal cells, the specific factors affecting the release of sporoplasm from spores should be determined. Thus, we investigated the effect of digestive and serum enzymes, fetal bovine serum (FBS), temperature, and the role of glucose in cell culture media on the release of sporoplasm. Sporoplasm release was observed in the groups treated with FBS and media containing glucose. In addition, 1,10-phenanthroline inhibited the release of sporoplasm in the FBS medium. These results indicate that K. septempunctata uses glucose for releasing its sporoplasm and that zinc or metalloprotease is related to the release mechanism. The present study provides important information for the development of agents to prevent sporoplasm release and the consequent food poisoning caused by K. septempunctata. PMID:25563617

  10. Drug release from ordered mesoporous silicas.

    PubMed

    Doadrio, Antonio L; Salinas, Antonio J; Sánchez-Montero, José M; Vallet-Regí, M

    2015-01-01

    The state-of-the-art in the investigation of drugs release from Silica-based ordered Mesoporous Materials (SMMs) is reviewed. First, the SMM systems used like host matrixes are described. Then, the model drugs studied until now, including their pharmacological action, structure and the mesoporous matrix employed for each drug, are comprehensively listed. Next, the factors influencing the release of drugs from SMMs and the strategies used to control the drug delivery, specially the chemical functionalization of the silica surface, are discussed. In addition, how all these factors were gathered in a kinetic equation that describes the drug release from the mesoporous matrixes is explained. The new application of molecular modeling and docking in the investigation of the drug delivery mechanisms from SMMs is also presented. Finally, the new approaches under investigation in this field are mentioned including the design of smart stimuli-responsive materials and other recent proposals for a future investigation. PMID:26549760

  11. Encapsulation of ketoprofen for controlled drug release.

    PubMed

    Arida, Adi I; Al-Tabakha, Moawia M

    2007-04-01

    Ketoprofen particles were encapsulated with polyions and gelatin to control the release of the drug in aqueous solutions. Charged linear polyions and gelatin were alternatively deposited on 6 microm drug microcrystals through layer-by-layer (LbL) assembly. Sequential layers of poly(dimethyldiallyl ammonium chloride) (PDDA) and poly(styrenesulfonate) (PSS) were followed by adsorption of two to six gelatin/PSS bilayers with corresponding capsule wall thicknesses ranging from 41 to 111 nm. The release of Ketoprofen from the coated microparticles was measured in aqueous solutions of pH 1.4, 4.1, and 7.4. The release rate has changed at these different pH values. At pH 7.4 the release rate of Ketoprofen from the encapsulated particles was less by 107 times compared to uncoated Ketoprofen. The results provide a method of achieving prolonged drug release through self-assembly of polymeric shells on drug crystals. PMID:17098404

  12. Drug release mechanisms of cast lipid implants.

    PubMed

    Kreye, F; Siepmann, F; Willart, J F; Descamps, M; Siepmann, J

    2011-08-01

    The aim of this work was to better understand which physicochemical processes are involved in the control of drug release from lipid implants prepared by melting and casting. Lipid implants gain steadily in importance as controlled parenteral drug delivery systems: In contrast to PLGA-based devices, no acidic microclimates are created, which can inactivate incorporated drugs. The melting and casting method offers various advantages over the commonly used direct compression technique. For example, powder de-mixing during manufacturing and highly challenging scale-up due to poor powder flowability are avoided. Importantly, broad spectra of drug release patterns can be easily provided by varying the type of lipid. The resulting drug release rates are generally lower than those of implants prepared by direct compression. This is probably due to the differences in the microstructure of the pore network of the systems. Drug or water diffusion plays a dominant role for the control of drug release, potentially combined with limited drug solubility effects, caused by the low amounts of water available within the implants. In the case of pure diffusion control, a mechanistic realistic mathematical theory is proposed, which allows for quantitative predictions of the effects of formulation parameters on the resulting drug release kinetics. Importantly, these theoretical predictions could be successfully confirmed by independent experiments. Thus, the obtained new insight into the underlying drug release mechanisms can significantly facilitate the optimization of this type of advanced drug delivery systems. This is particularly helpful if long release periods are targeted, requiring time-consuming experimental studies. PMID:21352913

  13. Electrospinning nanofibers for controlled drug release

    NASA Astrophysics Data System (ADS)

    Banik, Indrani

    Electrospinning is the most widely studied technique for the synthesis of nanofibers. Electrospinning is considered as one of the technologies that can produce nanosized drugs incorporated in polymeric nanofibers. In vitro and in vivo studies have demonstrated that the release rates of drugs from these nanofiber formulations are enhanced compared to those from original drug substance. This technology has the potential for enhancing the oral delivery of poorly soluble drugs. The electrospun mats were made using Polycaprolactone/PCL, Poly(DL-lactide)/PDL 05 and Poly(DL-lactide-co-glycolide)/PLGA. The drugs incorporated in the electrospun fibers were 5-Fluorouracil and Rapamycin. The evidence of the drugs being embedded in the polymers was obtained by scanning electron microscopy (SEM), Raman and infrared spectroscopy. The release of 5-Fluorouracil and Rapamycin were followed by UV-VIS spectroscopy.

  14. Nanotechnologies for Noninvasive Measurement of Drug Release

    PubMed Central

    Moore, Thomas; Chen, Hongyu; Morrison, Rachel; Wang, Fenglin; Anker, Jeffrey N.; Alexis, Frank

    2014-01-01

    A wide variety of chemotherapy and radiotherapy agents are available for treating cancer, but a critical challenge is to deliver these agents locally to cancer cells and tumors while minimizing side effects from systemic delivery. Nanomedicine uses nanoparticles with diameters in the range of ~1–100 nm to encapsulate drugs and target them to tumors. The nanoparticle enhances local drug delivery effciency to the tumors via entrapment in leaky tumor vasculature, molecular targeting to cells expressing cancer biomarkers, and/or magnetic targeting. In addition, the localization can be enhanced using triggered release in tumors via chemical, thermal, or optical signals. In order to optimize these nanoparticle drug delivery strategies, it is important to be able to image where the nanoparticles distribute and how rapidly they release their drug payloads. This Review aims to evaluate the current state of nanotechnology platforms for cancer theranostics (therapeutic and diagnostic particles) that are capable of noninvasive measurement of release kinetics. PMID:24215280

  15. Analysis of drug effects on neurotransmitter release

    SciTech Connect

    Rowell, P.; Garner, A.

    1986-03-05

    The release of neurotransmitter is routinely studied in a superfusion system in which serial samples are collected and the effects of drugs or other treatments on the amount of material in the superfusate is determined. With frequent sampling interval, this procedure provides a mechanism for dynamically characterizing the release process itself. Using automated data collection in conjunction with polyexponential computer analysis, the equation which describes the release process in each experiment is determined. Analysis of the data during the nontreated phase of the experiment allows an internal control to be used for accurately assessing any changes in neurotransmitter release which may occur during a subsequent treatment phase. The use of internal controls greatly improves the signal to noise ratio and allows determinations of very low concentrations of drugs on small amounts of tissue to be made. In this presentation, the effects of 10 ..mu..M nicotine on /sup 3/H-dopamine release in rat nucleus accumbens is described. The time course, potency and efficacy of the drug treatment is characterized using this system. Determinations of the exponential order of the release as well as the rate constants allow one to study the mechanism of the release process. A description of /sup 3/H-dopamine release in normal as well as Ca/sup + +/-free medium is presented.

  16. Phasic dopamine release in appetitive behaviors and drug abuse

    PubMed Central

    Wanat, Matthew J.; Willuhn, Ingo; Clark, Jeremy J.; Phillips, Paul E. M.

    2010-01-01

    Short phasic bursts of neuronal activity in dopamine neurons produce rapid and transient increases in extracellular dopamine concentrations throughout the mesocorticolimbic system, which are associated with the initiation of goal-directed behaviors. It is well established that acute exposure to many addictive drugs produce increases in tonic dopamine levels that occur on the order of minutes. However, recent studies suggest that abused drugs similarly enhance phasic dopamine release events that occur on a subsecond time scale. Furthermore, drug experience modulates the synaptic and intrinsic properties of dopamine neurons, which could affect dopamine burst firing and phasic dopamine release. This review will provide a general introduction to the mesolimbic dopamine system, as well as the primary methods used to detect dopamine neurons and dopamine release. We present the role of phasic dopamine release in appetitive behaviors in the context of contemporary theories regarding the function of dopamine. Next we discuss the known drug-induced changes to dopamine neurons and phasic release in both in vitro and in vivo preparations. Finally, we offer a simple model that chronic drug experience attenuates tonic/basal dopamine levels but promotes phasic dopamine release, which may result in aberrant goal-directed behaviors contributing to the development of addiction. PMID:19630749

  17. Layered superhydrophobic meshes for controlled drug release.

    PubMed

    Falde, Eric J; Freedman, Jonathan D; Herrera, Victoria L M; Yohe, Stefan T; Colson, Yolonda L; Grinstaff, Mark W

    2015-09-28

    Layered superhydrophobic electrospun meshes composed of poly(ε-caprolactone) (PCL) and poly(glycerol monostearate-co-ε-caprolactone) (PGC-C18) are described as a local source of chemotherapeutic delivery. Specifically, the chemotherapeutic agent SN-38 is incorporated into a central 'core' layer, between two 'shield' layers of mesh without drug. This mesh is resistant to wetting of the surface and throughout the bulk due to the pronounced hydrophobicity imparted by the high roughness of a hydrophobic polymer, PGC-C18. In serum solution, these meshes exhibit slow initial drug release over 10days corresponding to media infiltrating the shield layer, followed by steady release over >30days, as the drug-loaded core layer is wetted. This sequence of events is supported by X-ray computed tomography imaging of a contrast agent solution infiltrating the mesh. In vitro cytotoxicity data collected with Lewis Lung Carcinoma (LLC) cells are consistent with this release profile, remaining cytotoxic for over 20days, longer than the unlayered version. Finally, after subcutaneous implantation in rats, histology of meshes with and without drug demonstrated good integration and lack of adverse reaction over 28days. The drug release rates, robust superhydrophobicity, in vitro cytotoxicity of SN-38 loaded meshes, and compatibility provide key design parameters for the development of an implantable chemotherapeutic-loaded device for the prevention of local lung cancer recurrence following surgical resection. PMID:26160309

  18. Infuence of Microstructure in Drug Release Behavior of Silica Nanocapsules

    PubMed Central

    Zoltan, Tamara

    2013-01-01

    Meso- and nanoporous structures are adequate matrices for controlled drug delivery systems, due to their large surface areas and to their bioactive and biocompatibility properties. Mesoporous materials of type SBA-15, synthesized under different pH conditions, and zeolite beta were studied in order to compare the different intrinsic morphological characteristics as pore size, pore connectivity, and pore geometry on the drug loading and release process. These materials were characterized by X-ray diffraction, nitrogen adsorption, scanning and transmission electron microscopy, and calorimetric measurements. Ibuprofen (IBU) was chosen as a model drug for the formulation of controlled-release dosage forms; it was impregnated into these two types of materials by a soaking procedure during different periods. Drug loading and release studies were followed by UV-Vis spectrophotometry. All nano- and mesostructured materials showed a similar loading behavior. It was found that the pore size and Al content strongly influenced the release process. These results suggest that the framework structure and architecture affect the drug adsorption and release properties of these materials. Both materials offer a good potential for a controlled delivery system of ibuprofen. PMID:23986870

  19. Infuence of microstructure in drug release behavior of silica nanocapsules.

    PubMed

    Gonzalez, Gema; Sagarzazu, Amaya; Zoltan, Tamara

    2013-01-01

    Meso- and nanoporous structures are adequate matrices for controlled drug delivery systems, due to their large surface areas and to their bioactive and biocompatibility properties. Mesoporous materials of type SBA-15, synthesized under different pH conditions, and zeolite beta were studied in order to compare the different intrinsic morphological characteristics as pore size, pore connectivity, and pore geometry on the drug loading and release process. These materials were characterized by X-ray diffraction, nitrogen adsorption, scanning and transmission electron microscopy, and calorimetric measurements. Ibuprofen (IBU) was chosen as a model drug for the formulation of controlled-release dosage forms; it was impregnated into these two types of materials by a soaking procedure during different periods. Drug loading and release studies were followed by UV-Vis spectrophotometry. All nano- and mesostructured materials showed a similar loading behavior. It was found that the pore size and Al content strongly influenced the release process. These results suggest that the framework structure and architecture affect the drug adsorption and release properties of these materials. Both materials offer a good potential for a controlled delivery system of ibuprofen. PMID:23986870

  20. Controlled drug release from hydrogel nanoparticle networks.

    PubMed

    Huang, Gang; Gao, Jun; Hu, Zhibing; St John, John V; Ponder, Bill C; Moro, Dan

    2004-02-10

    Monodisperse nanoparticles of poly-N-isopropylacrylamide-co-allylamine (PNIPAM-co-allylamine) and PNIPAM-co-acrylic acid (PNIPAM-co-AA) were synthesized. The close-packed PNIPAM-co-allylamine and PNIPAM-co-AA nanoparticles were converted to three-dimensional gel networks by covalently crosslinking neighboring particles at room temperature and neutral pH using glutaric dialdehyde and adipic acid dihydrazide, respectively. Controlled release studies were conducted using dextran markers of various molecular weights as model macromolecular drugs. Release was quantified under various physical conditions, including a range of temperatures and dextran molecular weights. Dextran, entrapped in cavities in the nanoparticle network, was released with a rate regulated by their molecular weights and cavity size. No release from a conventional bulk PNIPAM gel, with high crosslinking density, was observed. The rate of release from the PNIPAM-co-allylamine network was temperature-dependent, being much faster at room temperature than that at human body temperature. In contrast, release of low molecular weight dextrans from the PNIPAM-co-AA network showed a temperature-independent release profile. These nanoparticle networks have several advantages over conventional bulk gels for controlling the release of high molecular weight biomolecules. PMID:14744482

  1. Marine Toxins Potently Affecting Neurotransmitter Release

    NASA Astrophysics Data System (ADS)

    Meunier, Frédéric A.; Mattei, César; Molgó, Jordi

    Synapses are specialised structures where interneuronal communication takes place. Not only brain function is absolutely dependent on synaptic activity, but also most of our organs are intimately controlled by synaptic activity. Synapses re therefore an ideal target to act upon and poisonous species have evolved fascinating neurotoxins capable of shutting down neuronal communication by blocking or activating essential components of the synapse. By hijacking key proteins of the communication machinery, neurotoxins are therefore extremely valuable tools that have, in turn, greatly helped our understanding of synaptic biology. Moreover, analysis and understanding of the molecular strategy used by certain neurotoxins has allowed the design of entirely new classes of drugs acting on specific targets with high selectivity and efficacy. This chapter will discuss the different classes of marine neurotoxins, their effects on neurotransmitter release and how they act to incapacitate key steps in the process leading to synaptic vesicle fusion.

  2. Drug-drug interactions affecting fluoroquinolones.

    PubMed

    Wijnands, G J; Vree, T B; Janssen, T J; Guelen, P J

    1989-12-29

    In a three-week study, the metabolism of the bronchodilator theophylline and its major metabolites formed by C-8 oxidation (1,3-dimethyluric acid) and N-demethylation (3-methylxanthine and 1-methyluric acid) was investigated in two healthy volunteers. Metabolic studies were performed following intravenous infusion of a single 6 mg/kg dose of aminophylline. During Week 1, theophylline was given alone (blank period), and during Weeks 2 and 3 it was given during oral coadministration of ofloxacin and enoxacin, respectively. Dosage of each quinolone was 200 mg twice daily for four days, starting three days prior to the theophylline infusion. During enoxacin coadministration, elimination half-lives of theophylline increased from 8.7 to 17.4 hours and from 6.1 to 12.3 hours, respectively. Total body clearance of theophylline decreased in both volunteers, whereas renal clearance did not alter. From this it was concluded that the decreased elimination results from a reduced metabolic clearance. During enoxacin coadministration, the formation of the metabolites 1-methyluric acid and 3-methylxanthine clearly was decreased, whereas the formation of 1,3-dimethyluric acid was less affected compared with the blank period. Interference with theophylline disposition by enoxacin is based predominantly on inhibition of microsomal N-demethylation. Ofloxacin comedication did not cause a change in the plasma parameters or renal excretion of theophylline and its metabolites compared with the blank period. PMID:2603893

  3. Fabrication of porous, drug-releasing, biodegradable, polymer scaffolds for sustained drug release.

    PubMed

    Uttarwar, Mayur; Aswath, Pranesh

    2008-10-01

    Two different approaches were used to fabricate porous scaffolds, and their in vitro drug releasing characteristics were examined. In the first method, a poly(L-lactic acid) (PLLA) solution and poly(vinyl alcohol) (PVA) + acetaminophen solution was homogenized. The emulsion was then blended with a PLLA solution in chloroform. The resultant emulsion was freeze-dried to form porous scaffolds. Various combinations were obtained by varying homogenizer speed and blender speed, and by varying the concentration of PVA and acetaminophen solutions. The in vitro drug-release study was performed for 6 days in a phosphate buffer. The influence of structure, porosity, and drug concentration of the scaffolds on drug-release rate was examined using design of experiments. In the second approach, scaffolds were prepared in layered constructs, with either a three-layered or five-layered structure. The PVA + acetaminophen solution was blended with PLLA solution using a blender. The drug-release study was performed for 19 days. The effect of drug concentration, blender speed, and the thickness of the layers on drug-release rate was examined. PMID:18437710

  4. Drug releasing systems in cardiovascular tissue engineering

    PubMed Central

    Spadaccio, Cristiano; Chello, Massimo; Trombetta, Marcella; Rainer, Alberto; Toyoda, Yoshiya; Genovese, Jorge A

    2009-01-01

    Abstract Heart disease and atherosclerosis are the leading causes of morbidity and mortality worldwide. The lack of suitable autologous grafts has produced a need for artificial grafts; however, current artificial grafts carry significant limitations, including thrombosis, infection, limited durability and the inability to grow. Tissue engineering of blood vessels, cardiovascular structures and whole organs is a promising approach for creating replacement tissues to repair congenital defects and/or diseased tissues. In an attempt to surmount the shortcomings of artificial grafts, tissue-engineered cardiovascular graft (TECVG), constructs obtained using cultured autologous vascular cells seeded onto a synthetic biodegradable polymer scaffold, have been developed. Autologous TECVGs have the potential advantages of growth, durability, resistance to infection, and freedom from problems of rejection, thrombogenicity and donor scarcity. Moreover polymers engrafted with growth factors, cytokines, drugs have been developed allowing drug-releasing systems capable of focused and localized delivery of molecules depending on the environmental requirements and the milieu in which the scaffold is placed. A broad range of applications for compound-releasing, tissue-engineered grafts have been suggested ranging from drug delivery to gene therapy. This review will describe advances in the development of drug-delivery systems for cardiovascular applications focusing on the manufacturing techniques and on the compounds delivered by these systems to date. PMID:19379142

  5. Software control of intelligent drug releases using stimuli-responsive release systems and IR data communication

    NASA Astrophysics Data System (ADS)

    Sakata, Shoei; Uchida, Kumao; Kaetsu, Isao; Kita, Yoshimi; Tsuji, Daisuke

    2007-04-01

    Intelligent drug delivery systems using UV polymerized hydrogels controlled by software were developed. The conditions of drug releases such as drug concentration, timing and amount of released drug could be controlled. It was also shown that the release threshold and the program design could be modified by IR data communication.

  6. Mesoporous silicon microparticles for oral drug delivery: loading and release of five model drugs.

    PubMed

    Salonen, J; Laitinen, L; Kaukonen, A M; Tuura, J; Björkqvist, M; Heikkilä, T; Vähä-Heikkilä, K; Hirvonen, J; Lehto, V-P

    2005-11-28

    Mesoporous silicon (PSi) microparticles were produced using thermal carbonization (TCPSi) or thermal oxidation (TOPSi) to obtain surfaces suitable for oral drug administration applications. The loading of five model drugs (antipyrine, ibuprofen, griseofulvin, ranitidine and furosemide) into the microparticles and their subsequent release behaviour were studied. Loading of drugs into TCPSi and TOPSi microparticles showed, that in addition to effects regarding the stability of the particles in the presence of aqueous or organic solvents, surface properties will affect compound affinity towards the particle. In addition to the surface properties, the chemical nature of the drug and the loading solution seems to be critical to the loading process. This was reflected in the obtained loading efficiencies, which varied between 9% and 45% with TCPSi particles. The release rate of a loaded drug from TCPSi microparticles was found to depend on the characteristic dissolution behaviour of the drug substance. When the dissolution rate of the free/unloaded drug was high, the microparticles caused a delayed release. However, with poorly dissolving drugs, the loading into the mesoporous microparticles clearly improved dissolution. In addition, pH dependency of the dissolution was reduced when the drug substance was loaded into the microparticles. PMID:16169628

  7. Effect of drug solubility and different excipients on floating behaviour and release from glyceryl monooleate matrices.

    PubMed

    Kumar M, Kiran; Shah, Manish H; Ketkar, Anant; Mahadik, K R; Paradkar, Anant

    2004-03-19

    Glycerol monooleate (GMO) matrix was found to be a gastro-retentive carrier system suitable for both polar and as well as non-polar drugs. Chlorpheniramine maleate (CPM) and diazepam (DZP) were used as model drugs. Effect of PEG 4000, PEG 10000, and stearic acid on floatability and release profile was studied. Water uptake increased with increase in the loading of polar drug (CPM) and decreased with non-polar drug (DZP). Similar effect was found to occur in case of drug release. PEGs increased the release up to certain concentration and decreased thereafter. Drug release decreased linearly with concentration of stearic acid. The type and extent of mesophases formed were significantly affected by the nature of drug, excipients and their concentration. Thus the selection of suitable excipients depending on polarity of drug, could help to modulate the floatability and release profile from GMO matrices. PMID:15019078

  8. Controlled drug release from Gelucire-based matrix pellets: experiment and theory.

    PubMed

    Siepmann, F; Muschert, S; Flament, M P; Leterme, P; Gayot, A; Siepmann, J

    2006-07-24

    The aim of this work was to elucidate the underlying drug release mechanisms from lipidic matrix pellets, using theophylline and Gelucire 50/02 as model drug and carrier material, respectively. Pellets were prepared by two different techniques: melt-solidification and extrusion-spheronization. The effects of different formulations and processing parameters on the resulting drug release kinetics in 0.1N HCl and phosphate buffer pH 7.4 were studied and the obtained results analyzed using adequate mathematical models in order to get further insight into the underlying mass transport mechanisms. The type of preparation technique was found to strongly affect the underlying drug release mechanisms. Drug release from pellets prepared by the melt-solidification method was primarily controlled by pure diffusion, whereas drug release from pellets prepared by the extrusion-spheronization method was purely diffusion-controlled only at early time points. After approximately 2h, the pellets started to disintegrate, resulting in decreased diffusion pathway lengths and, thus, increased drug release rates. Furthermore, the curing conditions significantly affected the theophylline release kinetics, whereas varying the initial drug loading from 20 to 50% (w/w) resulted only in a slight increase in the relative drug release rate. Interestingly, the effects of the size of pellets prepared by the melt-solidification method on the resulting drug release kinetics could be quantitatively predicted using an analytical solution of Fick's second law of diffusion. These predictions could be verified by independent experiments. PMID:16621362

  9. Similarity solution of a Stefan drug-release subdiffusion problem

    NASA Astrophysics Data System (ADS)

    Volpert, V. A.; Nepomnyashchy, A. A.

    2016-04-01

    Propagation of a gel/glass transition boundary in a polymer is considered in the context of drug release. Drug molecules are assumed to undergo subdiffusive motion in the gel and be quiescent in the glass region. Exact self-similar solutions for the drug concentration are constructed, and the amount of released drug is determined as a function of time.

  10. 21 CFR 343.90 - Dissolution and drug release testing.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Dissolution and drug release testing. 343.90 Section 343.90 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE INTERNAL ANALGESIC, ANTIPYRETIC, AND ANTIRHEUMATIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Testing Procedures §...

  11. Controlled release of an anti-cancer drug from DNA structured nano-films

    NASA Astrophysics Data System (ADS)

    Cho, Younghyun; Lee, Jong Bum; Hong, Jinkee

    2014-02-01

    We demonstrate the generation of systemically releasable anti-cancer drugs from multilayer nanofilms. Nanofilms designed to drug release profiles in programmable fashion are promising new and alternative way for drug delivery. For the nanofilm structure, we synthesized various unique 3-dimensional anti cancer drug incorporated DNA origami structures (hairpin, Y, and X shaped) and assembled with peptide via layer-by-layer (LbL) deposition method. The key to the successful application of these nanofilms requires a novel approach of the influence of DNA architecture for the drug release from functional nano-sized surface. Herein, we have taken first steps in building and controlling the drug incorporated DNA origami based multilayered nanostructure. Our finding highlights the novel and unique drug release character of LbL systems in serum condition taken full advantages of DNA origami structure. This multilayer thin film dramatically affects not only the release profiles but also the structure stability in protein rich serum condition.

  12. Controlled release of an anti-cancer drug from DNA structured nano-films

    PubMed Central

    Cho, Younghyun; Lee, Jong Bum; Hong, Jinkee

    2014-01-01

    We demonstrate the generation of systemically releasable anti-cancer drugs from multilayer nanofilms. Nanofilms designed to drug release profiles in programmable fashion are promising new and alternative way for drug delivery. For the nanofilm structure, we synthesized various unique 3-dimensional anti cancer drug incorporated DNA origami structures (hairpin, Y, and X shaped) and assembled with peptide via layer-by-layer (LbL) deposition method. The key to the successful application of these nanofilms requires a novel approach of the influence of DNA architecture for the drug release from functional nano-sized surface. Herein, we have taken first steps in building and controlling the drug incorporated DNA origami based multilayered nanostructure. Our finding highlights the novel and unique drug release character of LbL systems in serum condition taken full advantages of DNA origami structure. This multilayer thin film dramatically affects not only the release profiles but also the structure stability in protein rich serum condition. PMID:24518218

  13. Drug-loaded electrospun mats of poly(vinyl alcohol) fibres and their release characteristics of four model drugs

    NASA Astrophysics Data System (ADS)

    Taepaiboon, Pattama; Rungsardthong, Uracha; Supaphol, Pitt

    2006-05-01

    Mats of PVA nanofibres were successfully prepared by the electrospinning process and were developed as carriers of drugs for a transdermal drug delivery system. Four types of non-steroidal anti-inflammatory drug with varying water solubility property, i.e. sodium salicylate (freely soluble in water), diclofenac sodium (sparingly soluble in water), naproxen (NAP), and indomethacin (IND) (both insoluble in water), were selected as model drugs. The morphological appearance of the drug-loaded electrospun PVA mats depended on the nature of the model drugs. The 1H-nuclear magnetic resonance results confirmed that the electrospinning process did not affect the chemical integrity of the drugs. Thermal properties of the drug-loaded electrospun PVA mats were analysed by differential scanning calorimetry and thermogravimetric analysis. The molecular weight of the model drugs played a major role on both the rate and the total amount of drugs released from the as-prepared drug-loaded electrospun PVA mats, with the rate and the total amount of the drugs released decreasing with increasing molecular weight of the drugs. Lastly, the drug-loaded electrospun PVA mats exhibited much better release characteristics of the model drugs than drug-loaded as-cast films.

  14. SU-F-19A-08: Optimal Time Release Schedule of In-Situ Drug Release During Permanent Prostate Brachytherapy

    SciTech Connect

    Cormack, R; Ngwa, W; Makrigiorgos, G; Tangutoori, S; Rajiv, K; Sridhar, S

    2014-06-15

    Purpose: Permanent prostate brachytherapy spacers can be used to deliver sustained doses of radiosentitizing drug directly to the target, in order to enhance the radiation effect. Implantable nanoplatforms for chemo-radiation therapy (INCeRTs) have a maximum drug capacity and can be engineered to control the drug release schedule. The optimal schedule for sensitization during continuous low dose rate irradiation is unknown. This work studies the optimal release schedule of drug for both traditional sensitizers, and those that work by suppressing DNA repair processes. Methods: Six brachytherapy treatment plans were used to model the anatomy, implant geometry and calculate the spatial distribution of radiation dose and drug concentrations for a range of drug diffusion parameters. Three state partial differential equations (cells healthy, damaged or dead) modeled the effect of continuous radiation (radiosensitivities α,β) and cellular repair (time tr) on a cell population. Radiosensitization was modeled as concentration dependent change in α,β or tr which with variable duration under the constraint of fixed total drug release. Average cell kill was used to measure effectiveness. Sensitization by means of both enhanced damage and reduced repair were studied. Results: Optimal release duration is dependent on the concentration of radiosensitizer compared to the saturation concentration (csat) above which additional sensitization does not occur. Long duration drug release when enhancing α or β maximizes cell death when drug concentrations are generally over csat. Short term release is optimal for concentrations below saturation. Sensitization by suppressing repair has a similar though less distinct trend that is more affected by the radiation dose distribution. Conclusion: Models of sustained local radiosensitization show potential to increase the effectiveness of radiation in permanent prostate brachytherapy. INCeRTs with high drug capacity produce the greatest

  15. Effect of drug release kinetics on nanoparticle therapeutic efficacy and toxicity.

    PubMed

    Sethi, Manish; Sukumar, Rohit; Karve, Shrirang; Werner, Michael E; Wang, Edina C; Moore, Dominic T; Kowalczyk, Sonya R; Zhang, Liangfang; Wang, Andrew Z

    2014-02-21

    The effects of nanoparticle (NP) properties, such as size, shape and surface charge, on their efficacy and toxicity have been studied extensively. However, the effect of controlled drug release on NP efficacy and toxicity has not been thoroughly evaluated in vivo. Our study aims to fill this knowledge gap. A key challenge in characterizing the relationship between drug release and therapeutic ratio is to fabricate NPs that differ only in their drug release profile but are otherwise identical. To overcome this challenge, we developed crosslinkable lipid shell (CLS) NPs, where the drug release kinetics can be modulated without changing any other NP property. Using CLS NPs with wortmannin and docetaxel as model drugs, we determined the relationship between the release kinetics and therapeutic efficacy and toxicity of the drugs. We have determined that drug release kinetics can affect the therapeutic efficacy of NP docetaxel and NP wortmannin in vitro and in vivo. Our study also demonstrates that a decrease in drug release kinetics can result in a decrease in the hepatotoxicity of CLS NP wortmannin. Using two model drugs, the current findings provide the first direct evidence that NP drug release profile is a critical factor in determining the NP therapeutics' efficacy and toxicity in vivo. PMID:24418914

  16. Drug loading and release on tumor cells using silk fibroin-albumin nanoparticles as carriers

    NASA Astrophysics Data System (ADS)

    Subia, B.; Kundu, S. C.

    2013-01-01

    Polymeric and biodegradable nanoparticles are frequently used in drug delivery systems. In this study silk fibroin-albumin blended nanoparticles were prepared using the desolvation method without any surfactant. These nanoparticles are easily internalized by the cells, reside within perinuclear spaces and act as carriers for delivery of the model drug methotrexate. Methotrexate loaded nanoparticles have better encapsulation efficiency, drug loading ability and less toxicity. The in vitro release behavior of methotrexate from the nanoparticles suggests that about 85% of the drug gets released after 12 days. The encapsulation and loading of a drug would depend on factors such as size, charge and hydrophobicity, which affect drug release. MTT assay and conjugation of particles with FITC demonstrate that the silk fibroin-albumin nanoparticles do not affect the viability and biocompatibility of cells. This blended nanoparticle, therefore, could be a promising nanocarrier for the delivery of drugs and other bioactive molecules.

  17. Programmable and on-demand drug release using electrical stimulation

    PubMed Central

    Yi, Y. T.; Sun, J. Y.; Lu, Y. W.; Liao, Y. C.

    2015-01-01

    Recent advancement in microfabrication has enabled the implementation of implantable drug delivery devices with precise drug administration and fast release rates at specific locations. This article presents a membrane-based drug delivery device, which can be electrically stimulated to release drugs on demand with a fast release rate. Hydrogels with ionic model drugs are sealed in a cylindrical reservoir with a separation membrane. Electrokinetic forces are then utilized to drive ionic drug molecules from the hydrogels into surrounding bulk solutions. The drug release profiles of a model drug show that release rates from the device can be electrically controlled by adjusting the stimulated voltage. When a square voltage wave is applied, the device can be quickly switched between on and off to achieve pulsatile release. The drug dose released is then determined by the duration and amplitude of the applied voltages. In addition, successive on/off cycles can be programmed in the voltage waveforms to generate consistent and repeatable drug release pulses for on-demand drug delivery. PMID:25825612

  18. Stimulus responsive drug release from polymer gel.. Controlled release of ionic drug from polyampholyte gel

    NASA Astrophysics Data System (ADS)

    Sutani, Kouichi; Kaetsu, Isao; Uchida, Kumao; Matsubara, Yoshio

    2002-07-01

    2-(Dimethylamino)ethyl methacrylate or Methacryloyloxyethyltrimethylammonium chloride as a cationic monomer was copolymerized by UV with anionic monomer such as acrylic acid (AAc), into a polyampholyte. The pH responsive swelling behaviour and the pH and electro-responsive drug release functions of polyampholyte were investigated. The result showed that a copolymer of cation rich composition swelled at acidic condition, and shrank at alkaline condition. On the other hand, an anion rich copolymer showed a reverse phenomenon. Polyampholyte proved to interact with an ionic drug both by ionic binding and physical adsorption.

  19. Controlled release of dual drug-loaded hydroxypropyl methylcellulose matrix tablet using drug-containing polymeric coatings.

    PubMed

    Lee, B J; Ryu, S G; Cui, J H

    1999-10-15

    A dual drug-loaded hydroxypropylmethylcellulose (HPMC) matrix tablet simultaneously containing drug in inner tablet core and outer coated layer was formulated using drug-containing aqueous-based polymeric Eudragit RS30D dispersions. Effects of coating levels, drug loadings in outer layers, amount and type of five plasticizers and talc concentration on the release characteristics were evaluated on the characteristics in simulated gastric fluid for 2 h followed by a study in intestinal fluids. Melatonin (MT) was selected as a model drug. The surface morphology of dual drug-loaded HPMC tablets using scanning electron microscope (SEM) was smooth, showing the distinct coated layer with about 75-microm coating thickness at the 15% coating level. Unlike the uncoated and conventionally coated HPMC tablet, the dual drug-loaded HPMC matrix tablet gave a biphasic linear release, showing a zero-order for 4 h (first) followed by another zero-order release when fitted using linear regression (r(2) = 0.99). As the coating levels (15, 25%) increased, the release rate was further decreased. The biphasic release profiles of dual drug-loaded HPMC matrix tablet was unchanged except when 25% coating level containing 0.5% drug concentration was applied. As the drug concentration in polymeric coating dispersion increased (0.25-1.0%), the amount of drug released increased. The time for the first linear release was also advanced. However, the biphasic release pattern was not changed. The biphasic release profiles of dual drug-loaded HPMC matrix tablet were highly modified, depending on the amount and type of five plasticizers. Talc (10-30%) in coating dispersion as an anti-sticking material did not affect the release profiles. The current dual drug-loaded HPMC matrix tablet, showing biphasic release profiles may provide an alternative to deliver drugs with circadian rhythmic behaviors in the body but needs to be further validated in future in human studies. The dual drug-loaded coating

  20. Drug loaded and ethylcellulose coated mesoporous silica for controlled drug release prepared using a pilot scale fluid bed system.

    PubMed

    Hacene, Youcef Chakib; Singh, Abhishek; Van den Mooter, Guy

    2016-06-15

    The goal of this study was to test the feasibility to load non-ordered, non-spherical mesoporous silica with the model drug paracetamol, and subsequently coat the loaded particles using one single pilot scale fluid bed system equipped with a Wurster insert. Mesoporous silica particles (Davisil(®)) with a size ranging from 310 to 500μm and an average pore diameter of 15nm were loaded with paracetamol to 18.8% drug content. Subsequently, loaded cores were coated with ethylcellulose to obtain controlled drug release. Coating processing variables were varied following a full factorial design and their effect on drug release was assessed. Increasing coating solution feed rate and decreasing fluidizing air temperature were found to increase drug release rates. Increasing pore former level and decreasing coating level were found to increase drug release rates. The release medium's osmolality was varied using different sodium chloride concentrations, which was found to affect drug release rates. The results of this study clearly indicate the potential of non-ordered, non-spherical mesoporous silica as a reservoir carrier for the controlled release of drugs. Although non-spherical, we were able to reproducibly coat this carrier using a bottom spray fluid bed system. However, a major hurdle that needs to be tackled is the attrition the material suffers from during fluid bed processing. PMID:27107901

  1. Evaluation of sodium alginate as drug release modifier in matrix tablets.

    PubMed

    Liew, Celine Valeria; Chan, Lai Wah; Ching, Ai Ling; Heng, Paul Wan Sia

    2006-02-17

    Alginates are useful natural polymers suitable for use in the design of pharmaceutical dosage forms. However, the effects of particle size, viscosity and chemical composition of alginates on drug release from alginate matrix tablets are not clearly understood. Hence, 17 grades of sodium alginate with different particle size distributions, viscosities and chemical compositions were used to prepare matrix tablets at various concentrations to screen the factors influencing drug release from such matrices. Particle size was found to have an influence on drug release from these matrices. Sodium alginate was subsequently classified into several size fractions and also cryogenically milled to produce smaller particle size samples. Cryogenic milling could be successfully applied to pulverize coarse alginate particles without changing the quality through degradation or segregation. This study showed the significance of each alginate property in modulating drug release: particle size is important in initial alginic acid gel barrier formation as it affected the extent of burst release; higher alginate viscosity slowed down drug release rate in the buffer phase but enhanced release rate in the acid phase; high M-alginate might be more advantageous than high-G-alginate in sustaining drug release; and, the effect of increasing alginate concentration was greater with larger alginate particles. This can serve as a framework for formulators working with alginates. Furthermore, the results showed that sodium alginate matrices can sustain drug release for at least 8 h, even for a highly water-soluble drug in the presence of a water-soluble excipient. PMID:16364576

  2. Core-Shell Chitosan Microcapsules for Programmed Sequential Drug Release.

    PubMed

    Yang, Xiu-Lan; Ju, Xiao-Jie; Mu, Xiao-Ting; Wang, Wei; Xie, Rui; Liu, Zhuang; Chu, Liang-Yin

    2016-04-27

    A novel type of core-shell chitosan microcapsule with programmed sequential drug release is developed by the microfluidic technique for acute gastrosis therapy. The microcapsule is composed of a cross-linked chitosan hydrogel shell and an oily core containing both free drug molecules and drug-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles. Before exposure to acid stimulus, the resultant microcapsules can keep their structural integrity without leakage of the encapsulated substances. Upon acid-triggering, the microcapsules first achieve burst release due to the acid-induced decomposition of the chitosan shell. The encapsulated free drug molecules and drug-loaded PLGA nanoparticles are rapidly released within 60 s. Next, the drugs loaded in the PLGA nanoparticles are slowly released for several days to achieve sustained release based on the synergistic effect of drug diffusion and PLGA degradation. Such core-shell chitosan microcapsules with programmed sequential drug release are promising for rational drug delivery and controlled-release for the treatment of acute gastritis. In addition, the microcapsule systems with programmed sequential release provide more versatility for controlled release in biomedical applications. PMID:27052812

  3. Determining drug release rates of hydrophobic compounds from nanocarriers.

    PubMed

    D'Addio, Suzanne M; Bukari, Abdallah A; Dawoud, Mohammed; Bunjes, Heike; Rinaldi, Carlos; Prud'homme, Robert K

    2016-07-28

    Obtaining meaningful drug release profiles for drug formulations is essential prior to in vivo testing and for ensuring consistent quality. The release kinetics of hydrophobic drugs from nanocarriers (NCs) are not well understood because the standard protocols for maintaining sink conditions and sampling are not valid owing to mass transfer and solubility limitations. In this work, a new in vitroassay protocol based on 'lipid sinks' and magnetic separation produces release conditions that mimic the concentrations of lipid membranes and lipoproteins in vivo, facilitates separation, and thus allows determination of intrinsic release rates of drugs from NCs. The assay protocol is validated by (i) determining the magnetic separation efficiency, (ii) demonstrating that sink condition requirements are met, and (iii) accounting for drug by completing a mass balance. NCs of itraconazole and cyclosporine A (CsA) were prepared and the drug release profiles were determined. This release protocol has been used to compare the drug release from a polymer stabilized NC of CsA to a solid drug NP of CsA alone. These data have led to the finding that stabilizing block copolymer layers have a retarding effect on drug release from NCs, reducing the rate of CsA release fourfold compared with the nanoparticle without a polymer coating.This article is part of the themed issue 'Soft interfacial materials: from fundamentals to formulation'. PMID:27298440

  4. Superhydrophobic coating to delay drug release from drug-loaded electrospun fibrous materials

    NASA Astrophysics Data System (ADS)

    Song, Botao; Xu, Shichen; Shi, Suqing; Jia, Pengxiang; Xu, Qing; Hu, Gaoli; Zhang, Hongxin; Wang, Cuiyu

    2015-12-01

    The drug-loaded electrospun fibrous materials showed attractive applications in biomedical fields; however, the serve burst release of drug from this kind of drug carrier limited its further applications. In this study, inspired by water strong repellency of superhydrophobic surface, the drug-loaded electrospun fibrous mat coated with superhydrophobic layer was constructed to retard and control drug release. The results indicated that the superhydrophobic coating could be simply fabricated on the drug-loaded electrospun mat by the electrospray approach, and the thickness of the superhydrophobic coating could be finely controlled by varying the deposition time. It was further found that, as compared with drug-loaded electrospun mats, drug released sustainably from the samples coated with superhydrophobic layer, and the drug release rate could be controlled by the thickness of superhydrophobic layer. In summary, the current approach of coating a superhydrophobic layer on the drug-loaded electrospun fibrous materials offered a fundament for drug sustained release.

  5. Novel sustained release microspheres for pulmonary drug delivery.

    PubMed

    Cook, Robert O; Pannu, Rupi K; Kellaway, Ian W

    2005-05-01

    A novel process for generating sustained release (SR) particles for pulmonary drug delivery is described. High purity nanoparticles of a hydrophilic, ionised drug are entrapped within hydrophobic microspheres using a spray-drying approach. Sustained release of the model drug, terbutaline sulphate (TS), from the microspheres was found to be proportional to drug loading and phospholipid content. Microspheres with a 33% drug loading exhibited sustained release of 32.7% over 180 min in phosphate buffer. Release was not significantly different in simulated lung fluids. No significant burst release was observed which suggested that nanoparticles were coated effectively during spray-drying. The absence of nanoparticles at the microsphere surface was confirmed with confocal microscopy. The sustained release microspheres were formulated as a carrier-free dry powder for inhalation, and exhibited a favourable Fine Particle Fraction (FPF) of 46.5+/-1.8% and Mass Median Aerodynamic Diameter (MMAD) of 3.93+/-0.12 microm. PMID:15866336

  6. New insight into modified release pellets - Internal structure and drug release mechanism.

    PubMed

    Ensslin, Simon; Moll, Klaus Peter; Paulus, Kurt; Mäder, Karsten

    2008-06-01

    The aim of the study was to explore the drug release mechanism from pellets, coated with blends of poly(vinyl acetate) (PVAc) and polyvinyl alcohol-polyethylene glycol graft copolymer (PVA-PEG). Water influx and drug solubilization inside the pellets were investigated in correlation to drug release. The highly soluble drug Chlorpheniramine maleate (CPM) was used as a model compound. Modified release pellets were manufactured by fluid bed drug layering and film coating of starter beads. The pellets were characterized using cross section EDX mapping, confirming location and homogeneity of the different layers. A film coat of 23%, containing PVAc/PVA-PEG in 9:1 ratio, resulted in a sigmoid shaped release curve with 2 h lag-time, followed by 3 h of continuous drug release. Using NMR analysis, water influx and drug solubilization inside the pellets were detected within 20 min. Additionally, dissolution of PVA-PEG after several minutes and drug release after the lag-time were measurable. A fast water influx into PVAc/PVA-PEG film coated pellets did not result in a fast drug release. Despite a fast drug solubilization within the pellets, drug release was initiated after 2 h, suggesting a one way stream of water during the observed lag-time. PMID:18433911

  7. Magnetically Actuated Soft Capsule With the Multimodal Drug Release Function.

    PubMed

    Yim, Sehyuk; Goyal, Kartik; Sitti, Metin

    2013-01-01

    In this paper, we present a magnetically actuated multimodal drug release mechanism using a tetherless soft capsule endoscope for the treatment of gastric disease. Because the designed capsule has a drug chamber between both magnetic heads, if it is compressed by the external magnetic field, the capsule could release a drug in a specific position locally. The capsule is designed to release a drug in two modes according to the situation. In the first mode, a small amount of drug is continuously released by a series of pulse type magnetic field (0.01-0.03 T). The experimental results show that the drug release can be controlled by the frequency of the external magnetic pulse. In the second mode, about 800 mm(3) of drug is released by the external magnetic field of 0.07 T, which induces a stronger magnetic attraction than the critical force for capsule's collapsing. As a result, a polymeric coating is formed around the capsule. The coated area is dependent on the drug viscosity. This paper presents simulations and various experiments to evaluate the magnetically actuated multimodal drug release capability. The proposed soft capsules could be used as minimally invasive tetherless medical devices with therapeutic capability for the next generation capsule endoscopy. PMID:25378896

  8. In vitro drug release mechanism and drug loading studies of cubic phase gels.

    PubMed

    Lara, Marilisa G; Bentley, M Vitória L B; Collett, John H

    2005-04-11

    Glyceryl monooleate/water cubic phase systems were investigated as drug delivery systems, using salicylic acid as a model drug. The liquid crystalline phases formed by the glyceryl monooleate (GMO)/water systems were characterized by polarizing microscopy. In vitro drug release studies were performed and the influences of initial water content, swelling and drug loading on the drug release properties were evaluated. Water uptake followed second-order swelling kinetics. In vitro release profiles showed Fickian diffusion control and were independent on the initial water content and drug loading, suggesting GMO cubic phase gels suitability for use as drug delivery system. PMID:15778062

  9. Continuous nanostructures for the controlled release of drugs.

    PubMed

    Venugopal, J; Prabhakaran, Molamma P; Low, Sharon; Choon, Aw Tar; Deepika, G; Dev, V R Giri; Ramakrishna, S

    2009-01-01

    The annual world wide market for controlled release of polymer systems which extends beyond drug delivery is now estimated to $60 billion and these systems are used by over 100 million people each year. It was estimated that drug delivery will play a pivotal role in approximately 40% of all pharmaceutical sales in near future. Novel methods of drug delivery will not only result in more effective and efficacious treatments but also generates new niche markets to provide greater intellectual property protection to already existing drug formulations. Recently, biodegradable electrospun polymer nanofibrous substrate as drug carrier seems to be a promising method for delivering anticancer drugs, especially in postoperative local chemotherapy. Alternatively drug release can be triggered by the environment or other external events such as changes in pH, temperature, or the presence of analyte such as glucose. In general, controlled release of polymer systems delivering drugs in the optimum dosage for long periods is to increase the efficacy of drug, reducing patient compliance. Recent research for the use of nanotechnology (nanoparticle and nanofibers) in drug delivery suggests that the technology might solve problems in the areas such as controlled release, various topical administration, gut absorption and targeted systemic delivery. This review article described the applications of polymer nanoparticles and nanofibers for loading potential drugs for the controlled release to target incurable diseases. PMID:19442191

  10. Drug release kinetic analysis and prediction of release data via polymer molecular weight in sustained release diltiazem matrices.

    PubMed

    Adibkia, K; Ghanbarzadeh, S; Mohammadi, G; Khiavi, H Z; Sabzevari, A; Barzegar-Jalali, M

    2014-03-01

    This study was conducted to investigate the effects of HPMC (K4M and K100M) as well as tragacanth on the drug release rate of diltiazem (DLTZ) from matrix tablets prepared by direct compression method.Mechanism of drug transport through the matrices was studied by fitting the release data to the 10 kinetic models. 3 model independent parameters; i. e., mean dissolution time (MDT), mean release rate (MRR) and release rate efficacy (RE) as well as 5 time point approaches were established to compare the dissolution profiles. To find correlation between fraction of drug released and polymer's molecular weight, dissolution data were fitted into two proposed equations.All polymers could sustain drug release up to 10 h. The release data were fitted best to Peppas and Higuchi square root kinetic models considering squared correlation coefficient and mean percent error (MPE). RE and MRR were decreased when polymer to drug ratio was increased. Conversely, t60% was increased with raising polymer /drug ratio. The fractions of drug released from the formulations prepared with tragacanth were more than those formulated using the same amount of HPMC K4M and HPMC K100M.Preparation of DLTZ matrices applying HPMCK4M, HPMC K100M and tragacanth could effectively extend the drug release. PMID:23986307

  11. Hybrid Nanogels for Sustainable Positive Thermosensitive Drug Release

    SciTech Connect

    Shin, Yongsoon ); Chang, Jeong H.; Liu, Jun; Williford, Rick E. ); Shin, Young-Kook; Exarhos, Gregory J. )

    2001-05-18

    A hybrid nanogel is developed based on interpenetrating networks of thermosensitive PNIPAAm gels and tailored nanoporous silica. Sustainable positive thermo-responsive drug release profile is obtained. When the temperature rises, the polymer gel shrinks, squeezing the drug into the porous channels, and at the same time, opening the pore to the outside media. The drug slowly diffuses out of the porous channels. The overall release rate can be adjusted by changing the composition of the nanogel.

  12. Effect of source variation on drug release from HPMC tablets: linear regression modeling for prediction of drug release.

    PubMed

    Piriyaprasarth, Suchada; Sriamornsak, Pornsak

    2011-06-15

    The aim of this study was to investigate the effect of source variation of hydroxypropyl methylcellulose (HPMC) raw material on prediction of drug release from HPMC matrix tablets. To achieve this objective, the flow ability (i.e., angle of repose and Carr's compressibility index) and apparent viscosity of HPMC from 3 sources was investigated to differentiate HPMC source variation. The physicochemical properties of drug and manufacturing process were also incorporated to develop the linear regression model for prediction of drug release. Specifically, the in vitro release of 18 formulations was determined according to a 2 × 3 × 3 full factorial design. Further regression analysis provided a quantitative relationship between the response and the studied independent variables. It was found that either apparent viscosity or Carr's compressibility index of HPMC powders combining with solubility and molecular weight of drug had significant impact on the release behavior of drug. The increased drug release was observed when a greater in drug solubility and a decrease in the molecular weight of drug were applied. Most importantly, this study has shown that the HPMC having low viscosity or high compressibility index resulted in an increase of drug release, especially in the case of poorly soluble drugs. PMID:21420475

  13. Controlled release niosome embedded chitosan system: effect of crosslink mesh dimensions on drug release.

    PubMed

    Williams, Eva Christabel; Toomey, Ryan; Alcantar, Norma

    2012-12-01

    We report on a model chemotherapy drug delivery system comprising nonionic surfactant vesicles (niosomes) packaged within a temperature-sensitive chitosan network. This smart packaging, or package-within-a package system, provides two distinct advantages. First, the gel prevents circulation of the niosomes and maintains delivery in the vicinity of a tumor. Second, the chitosan network protects the niosomes against fluctuations in tonicity, which affects delivery rates. Tonicity is the sum of the concentrations of the solutes which have the capacity to exert an osmotic force across the membrane. All release rate experiments were conducted with 5,6-carboxyfluorescein, a fluorescent dye. Release rates were monitored from both bare niosomes alone and niosome-embedded, chitosan networks. It was observed that chitosan networks prolonged delivery from 100 h to 55 days in low ionic strength environment and pH conditions similar to a tumor site. The primary effect of chitosan is to add control on release time and dosage, and stabilize the niosomes through a high ionic strength surrounding that prevents uncontrolled bursting of the niosomes. Secondary factors include crosslink density of the chitosan network, molecular weight of the individual chitosan polymers, dye concentration within the niosomes, and the number density of niosomes packaged within the chitosan network. Each of these factors can be altered to fine-tune release rates. PMID:22733611

  14. Compression of coated drug beads for sustained release tablet of glipizide: formulation, and dissolution.

    PubMed

    Nguyen, Chien; Christensen, J Mark; Ayres, James W

    2014-02-01

    A promising glipizide formulation comprising compression of four-layer coated beads into tablets was prepared. The tablet offered the advantages of: a two-hour lag time before drug release, retaining sustained release characteristics and providing approximately zero-order drug release. Drug release was nearly independent of paddle speeds of 50 and 100 rpm releasing 80% over 14 h similar to the commercial glipizide osmotic pump tablet during dissolution testing while keeping the benefits of multiparticular dosage forms. The tablets contain beads with four layers: (1) the innermost layer consists of 2.5 g glipizide and 3.75 g solid ethylcellulose (Surelease®) coated onto 71.25 g of sugar beads; (2) next a hardening layer of 5 g of hypromellose; (3) the controlled release layer of 7.5 g of Surelease®:lactose at a solids ratio of 100:7 and (4) an outermost layer of 20 g of lactose:sodium starch glycolate (Explotab®) at a 2:1 ratio. Then, beads were compressed into tablets containing 11 mg of glipizide using 1500 lbs of compression pressure. The dissolution test similarity factor (f2) was above 50 for all test conditions for formulation F13 and Glucotrol® with a high of 69.9. The two Surelease® layers both aid controlling drug release, with the Surelease®-drug layer affecting drug release to a greater extent. PMID:23259589

  15. Investigating the feasibility of temperature-controlled accelerated drug release testing for an intravaginal ring.

    PubMed

    Externbrink, Anna; Clark, Meredith R; Friend, David R; Klein, Sandra

    2013-11-01

    The objective of the present study was to investigate if temperature can be utilized to accelerate drug release from Nuvaring®, a reservoir type intravaginal ring based on polyethylene vinyl acetate copolymer that releases a constant dose of contraceptive steroids over a duration of 3 weeks. The reciprocating holder apparatus (USP 7) was utilized to determine real-time and accelerated etonogestrel release from ring segments. It was demonstrated that drug release increased with increasing temperature which can be attributed to enhanced drug diffusion. An Arrhenius relationship of the zero-order release constants was established, indicating that temperature is a valid parameter to accelerate drug release from this dosage form and that the release mechanism is maintained under these accelerated test conditions. Accelerated release tests are particularly useful for routine quality control to assist during batch release of extended release formulations that typically release the active over several weeks, months or even years, since they can increase the product shelf life. The accelerated method should therefore be able to discriminate between formulations with different release characteristics that can result from normal manufacturing variance. In the case of Nuvaring®, it is well known that the process parameters during the extrusion process strongly influence the polymeric structure. These changes in the polymeric structure can affect the permeability which, in turn, is reflected in the release properties. Results from this study indicate that changes in the polymeric structure can lead to a different temperature dependence of the release rate, and as a consequence, the accelerated method can become less sensitive to detect changes in the release properties. When the accelerated method is utilized during batch release, it is therefore important to take this possible restriction into account and to evaluate the accelerated method with samples from non

  16. Bioerodible system for sequential release of multiple drugs.

    PubMed

    Sundararaj, Sharath C; Thomas, Mark V; Dziubla, Thomas D; Puleo, David A

    2014-01-01

    Because many complex physiological processes are controlled by multiple biomolecules, comprehensive treatment of certain disease conditions may be more effectively achieved by administration of more than one type of drug. Thus, the objective of the present research was to develop a multilayered, polymer-based system for sequential delivery of multiple drugs. The polymers used were cellulose acetate phthalate (CAP) complexed with Pluronic F-127 (P). After evaluating morphology of the resulting CAPP system, in vitro release of small molecule drugs and a model protein was studied from both single and multilayered devices. Drug release from single-layered CAPP films followed zero-order kinetics related to surface erosion of the association polymer. Release studies from multilayered CAPP devices showed the possibility of achieving intermittent release of one type of drug as well as sequential release of more than one type of drug. Mathematical modeling accurately predicted the release profiles for both single layer and multilayered devices. The present CAPP association polymer-based multilayer devices can be used for localized, sequential delivery of multiple drugs for the possible treatment of complex disease conditions, and perhaps for tissue engineering applications, that require delivery of more than one type of biomolecule. PMID:24096151

  17. Effect of drug release kinetics on nanoparticle therapeutic efficacy and toxicity

    NASA Astrophysics Data System (ADS)

    Sethi, Manish; Sukumar, Rohit; Karve, Shrirang; Werner, Michael E.; Wang, Edina C.; Moore, Dominic T.; Kowalczyk, Sonya R.; Zhang, Liangfang; Wang, Andrew Z.

    2014-01-01

    The effects of nanoparticle (NP) properties, such as size, shape and surface charge, on their efficacy and toxicity have been studied extensively. However, the effect of controlled drug release on NP efficacy and toxicity has not been thoroughly evaluated in vivo. Our study aims to fill this knowledge gap. A key challenge in characterizing the relationship between drug release and therapeutic ratio is to fabricate NPs that differ only in their drug release profile but are otherwise identical. To overcome this challenge, we developed crosslinkable lipid shell (CLS) NPs, where the drug release kinetics can be modulated without changing any other NP property. Using CLS NPs with wortmannin and docetaxel as model drugs, we determined the relationship between the release kinetics and therapeutic efficacy and toxicity of the drugs. We have determined that drug release kinetics can affect the therapeutic efficacy of NP docetaxel and NP wortmannin in vitro and in vivo. Our study also demonstrates that a decrease in drug release kinetics can result in a decrease in the hepatotoxicity of CLS NP wortmannin. Using two model drugs, the current findings provide the first direct evidence that NP drug release profile is a critical factor in determining the NP therapeutics' efficacy and toxicity in vivo.The effects of nanoparticle (NP) properties, such as size, shape and surface charge, on their efficacy and toxicity have been studied extensively. However, the effect of controlled drug release on NP efficacy and toxicity has not been thoroughly evaluated in vivo. Our study aims to fill this knowledge gap. A key challenge in characterizing the relationship between drug release and therapeutic ratio is to fabricate NPs that differ only in their drug release profile but are otherwise identical. To overcome this challenge, we developed crosslinkable lipid shell (CLS) NPs, where the drug release kinetics can be modulated without changing any other NP property. Using CLS NPs with

  18. Drug encapsulation and release behavior of telechelic nanoparticles

    NASA Astrophysics Data System (ADS)

    Zhang, Shimiao; Arshad, Muhammad; Ullah, Aman

    2015-10-01

    The encapsulation and release of hydrophobic drug, carbamazepine (CBZ) was investigated using three previously synthesized amphiphilic Lipid-b-poly(ethylene glycol) (Lipid-PEG) conjugates. Their micellization, drug encapsulation, and release behavior was investigated by dynamic light scattering (DLS), transmission electron microscope (TEM), and fluorescence spectroscopy. The highest capacity of drug entrapment was observed for the CPE-PEG-a telechelic with the shorter PEG block and the size of the nanoparticles decreased evidently after the drug was loaded, while a slight decrease in size was also observed for the CPE-PEG-b telechelic with longer PEG block and the three-armed CPE-GE conjugate. TEM images showed that all three types of the drug-loaded micelles had spherical or near-spherical morphology. In the study of the in vitro drug release, slower drug-release patterns were observed for CPE-PEG-a and CPE-GE micelles. Almost all the drug entrapped inside the three types of micelles could be released within 50 h.

  19. Preparation of hybrid materials for controlled drug release.

    PubMed

    Milczewska, Kasylda; Voelkel, Adam; Zwolińska, Joanna; Jędro, Dorota

    2016-07-01

    Authors obtained hybrid organic-inorganic materials applied in sustained drug delivery. The materials are ibuprofen as a model drug, hydroxyapatite and three different polymers as supports. Influence of the type of employed polymer, an inorganic carrier, on the properties and drug release profiles was estimated. Flory-Huggins interaction parameters, the dispersive component of surface free energy and acid-base characteristic of the surface were used to assess the behavior of the composites in terms of drug release. The experiments were carried out with the use of inverse gas chromatography (IGC), Fourier transform infrared (FTIR) and ultraviolet (UV) techniques. FTIR and ATR-FTIR spectra were collected. The values of [Formula: see text] parameter obtained for all investigated materials (excluding poly(L-lactide) (PLA2)) indicate low or medium activity. The strongest interactions (the lowest values of the Flory-Huggins [Formula: see text] parameter) are observed for PLA2 composition, while the weakest interactions for systems with polyethylene glycol (PEG). Finally, drug release profiles are shown. For materials prepared with Eudragit® (EUD) and PLA, the release of drug was much smaller, which corresponds to lower values of Flory-Huggins parameter. The executed experiments allowed the estimation of the properties of prepared composites. Prepared materials present properties required in sustained drug release and may be successfully applied as drug delivery systems. PMID:26559181

  20. Effect of Antiadherents on the Physical and Drug Release Properties of Acrylic Polymeric Films.

    PubMed

    Ammar, Hussein O; Ghorab, Mamdouh M; Felton, Linda A; Gad, Shadeed; Fouly, Aya A

    2016-06-01

    Antiadherents are used to decrease tackiness of a polymer coating during both processing and subsequent storage. Despite being a common excipient in coating formulae, antiadherents may affect mechanical properties of the coating film as well as drug release from film-coated tablets, but how could addition of antiadherents affect these properties and to what extent and is there a relation between the physical characteristics of the tablet coat and the drug release mechanisms? The aim of this study was to evaluate physical characteristics of films containing different amounts of the antiadherents talc, glyceryl monostearate, and PlasACRYL(TM) T20. Eudragit RL30D and Eudragit RS30D as sustained release polymers and Eudragit FS30D as a delayed release material were used. Polymer films were characterized by tensile testing, differential scanning calorimetry (DSC), microscopic examination, and water content as calculated from loss on drying. The effect of antiadherents on in vitro drug release for the model acetylsalicylic acid tablets coated with Eudragit FS30D was also determined. Increasing talc concentration was found to decrease the ability of the polymer films to resist mechanical stress. In contrast, glyceryl monostearate (GMS) and PlasACRYL produced more elastic films. Talc at concentrations higher than 25% caused negative effects, which make 25% concentration recommended to be used with acrylic polymers. All antiadherents delayed the drug release at all coating levels; hence, different tailoring of drug release may be achieved by adjusting antiadherent concentration with coating level. PMID:26314244

  1. Mechanism of drug release from poly(L-lactic acid) matrix containing acidic or neutral drugs.

    PubMed

    Miyajima, M; Koshika, A; Okada, J; Ikeda, M

    1999-08-01

    The release profiles of acidic and neutral drugs from poly(L-lactic acid) [P(L)LA] matrices were investigated to reveal their release mechanism. Cylindrical matrices (rods; 10 mmx1 mm diameter) were prepared by the heat compression method. The acidic and neutral drugs investigated were dissolved in the P(L)LA rods. It was found that the release profiles consisted of two sequential stages. At the first release stage, P(L)LA remained in an amorphous state and the drugs diffused through the hydrated matrices. At the second release stage, P(L)LA transformed to a semicrystalline state and the drugs diffused through water-filled micropores developed by polymer crystallization. In addition, the drugs were also found to precipitate out as crystals in the rods, resulting in a transformation of the rods into drug-dispersed matrices. On the basis of these findings, we derived a modified diffusion equation for the drug release at the second stage. This equation showed good fits to the release profiles of these drugs. Furthermore, the availability of the derived equation was supported by the acceleration in the fractional drug release rate noted both with decreases in the drug content in the rod and increases in the pH of the medium. PMID:10425326

  2. Mathematical modeling of drug release from lipid dosage forms.

    PubMed

    Siepmann, J; Siepmann, F

    2011-10-10

    Lipid dosage forms provide an interesting potential for controlled drug delivery. In contrast to frequently used poly(ester) based devices for parenteral administration, they do not lead to acidification upon degradation and potential drug inactivation, especially in the case of protein drugs and other acid-labile active agents. The aim of this article is to give an overview on the current state of the art of mathematical modeling of drug release from this type of advanced drug delivery systems. Empirical and semi-empirical models are described as well as mechanistic theories, considering diffusional mass transport, potentially limited drug solubility and the leaching of other, water-soluble excipients into the surrounding bulk fluid. Various practical examples are given, including lipid microparticles, beads and implants, which can successfully be used to control the release of an incorporated drug during periods ranging from a few hours up to several years. The great benefit of mechanistic mathematical theories is the possibility to quantitatively predict the effects of different formulation parameters and device dimensions on the resulting drug release kinetics. Thus, in silico simulations can significantly speed up product optimization. This is particularly useful if long release periods (e.g., several months) are targeted, since experimental trial-and-error studies are highly time-consuming in these cases. In the future it would be highly desirable to combine mechanistic theories with the quantitative description of the drug fate in vivo, ideally including the pharmacodynamic efficacy of the treatments. PMID:21802501

  3. Extended Release of Native Drug Conjugated in Polyketal Microparticles.

    PubMed

    Guo, Shutao; Nakagawa, Yoshiyuki; Barhoumi, Aoune; Wang, Weiping; Zhan, Changyou; Tong, Rong; Santamaria, Claudia; Kohane, Daniel S

    2016-05-18

    Polyketals, which can be biodegradable, have good biocompatibility, and are pH-sensitive, could have broad applicability in drug delivery and other biomedical applications. However, facile synthesis of high molecular weight polyketals is challenging, and short durations of drug release from polyketal particulate formulations limit their application in drug delivery. Here we report the synthesis of a di-isopropenyl ether monomer and its use to synthesize high molecular weight estradiol-polyketal conjugates by addition polymerization. Microparticles were prepared from the estradiol-polyketal conjugate, where estradiol was incorporated into the polymer backbone. The particles had high drug loading and significantly prolonged drug release. Release of estradiol from the drug-polyketal conjugate microparticles was acid-responsive, as evidenced by faster drug release at low pH and with co-incorporation of PLGA. Tissue reaction to the microparticles was benign in vivo. Polyketal drug conjugates are promising candidates for long-acting drug delivery systems to treat chronic diseases. PMID:27148927

  4. Polymeric nanoparticles containing diazepam: preparation, optimization, characterization, in-vitro drug release and release kinetic study

    NASA Astrophysics Data System (ADS)

    Bohrey, Sarvesh; Chourasiya, Vibha; Pandey, Archna

    2016-03-01

    Nanoparticles formulated from biodegradable polymers like poly(lactic-co-glycolic acid) (PLGA) are being extensively investigated as drug delivery systems due to their two important properties such as biocompatibility and controlled drug release characteristics. The aim of this work to formulated diazepam loaded PLGA nanoparticles by using emulsion solvent evaporation technique. Polyvinyl alcohol (PVA) is used as stabilizing agent. Diazepam is a benzodiazepine derivative drug, and widely used as an anticonvulsant in the treatment of various types of epilepsy, insomnia and anxiety. This work investigates the effects of some preparation variables on the size and shape of nanoparticles prepared by emulsion solvent evaporation method. These nanoparticles were characterized by photon correlation spectroscopy (PCS), transmission electron microscopy (TEM). Zeta potential study was also performed to understand the surface charge of nanoparticles. The drug release from drug loaded nanoparticles was studied by dialysis bag method and the in vitro drug release data was also studied by various kinetic models. The results show that sonication time, polymer content, surfactant concentration, ratio of organic to aqueous phase volume, and the amount of drug have an important effect on the size of nanoparticles. Hopefully we produced spherical shape Diazepam loaded PLGA nanoparticles with a size range under 250 nm with zeta potential -23.3 mV. The in vitro drug release analysis shows sustained release of drug from nanoparticles and follow Korsmeyer-Peppas model.

  5. Swelling and drug release from oral thin films (OTFs)

    NASA Astrophysics Data System (ADS)

    Adrover, A.; Casadei, M. A.; Paolicelli, P.; Petralito, S.; Varani, G.

    2016-05-01

    We investigate the characteristic time-scales for swelling and drug release from polymeric thin films for buccal delivery. In this work, novel OTFs were prepared combining Gellan gum, a natural polysaccharide well known in the pharmaceutical field, along with Glycerol, used as plasticizer. A new millifluidic flow-through device is adopted for in-vitro release tests.

  6. Mechanisms of drug release in citrate buffered HPMC matrices.

    PubMed

    Pygall, Samuel R; Kujawinski, Sarah; Timmins, Peter; Melia, Colin D

    2009-03-31

    Few studies report the effects of alkalizing buffers in HPMC matrices. These agents are incorporated to provide micro-environmental buffering, protection of acid-labile ingredients, or pH-independent release of weak acid drugs. In this study, the influence of sodium citrate on the release kinetics, gel layer formation, internal gel pH and drug release mechanism was investigated in HPMC 2910 and 2208 (Methocel E4M and K4M) matrices containing 10% felbinac 39% HPMC, dextrose and sodium citrate. Matrix dissolution at pH 1.2 and pH 7.5 resulted in complex release profiles. HPMC 2910 matrices exhibited biphasic release, with citrate increasing the immediate release phase (<60min) and reducing the extended release. HPMC 2208 matrices were accelerated, but without the loss of extended release characteristics. Studies of early gel layer formation suggested gel barrier disruption and enhanced liquid penetration. pH modification of the gel layer was transitory (<2h) and corresponded temporally with the immediate release phase. Results suggest that in HPMC 2910 matrices, high initial citrate concentrations within the gel layer suppress particle swelling, interfere with diffusion barrier integrity, but are lost rapidly whereupon drug solubility reduces and the diffusion barrier recovers. These Hofmeister or osmotic-mediated effects are better resisted by the less methoxylated HPMC 2208. PMID:19100822

  7. Photocatalytic Degradation of Cell Membrane Coatings for Controlled Drug Release.

    PubMed

    Rao, Lang; Meng, Qian-Fang; Huang, Qinqin; Liu, Pei; Bu, Lin-Lin; Kondamareddy, Kiran Kumar; Guo, Shi-Shang; Liu, Wei; Zhao, Xing-Zhong

    2016-06-01

    Biomimetic cell-membrane-camouflaged particles with desirable features have been widely used for various biomedical applications. However, there are few reports on employing these particles for cancer drug delivery due to the failure of the membrane coatings to be efficiently degraded in the tumor microenvironment which hampers the drug release. In this work, core-shell SiO2 @TiO2 nanoparticles with enhanced photocatalytic activity are used for controlled degradation of surface erythrocyte membrane coatings. The antitumor drug docetaxel is encapsulated into nanocarriers to demonstrate the controlled drug release under ultraviolet irradiation, and the drug-loaded nanoparticles are further used for enhanced cancer cell therapy. Here, a simple but practical method for degradation of cell membrane coatings is presented, and a good feasibility of using cell membrane-coated nanocarriers for controlled drug delivery is demonstrated. PMID:27191802

  8. Spherical and tubule nanocarriers for sustained drug release

    PubMed Central

    Shutava, T.; Fakhrullin, R.; Lvov, Y.

    2014-01-01

    We discuss new trends in Layer-by-Layer (LbL) encapsulation of spherical and tubular cores of 50–150 nm diameter and loaded with drugs. This core size decrease (from few micrometers to a hundred of nanometers) for LbL encapsulation required development of sonication assistant non-washing technique and shell PEGylation to reach high colloidal stability of drug nanocarriers at 2–3 mg/mL concentration in isotonic buffers and serum. For 120–170 nm spherical LbL nanocapsules of low soluble anticancer drugs, polyelectrolyte shell thickness controls drug dissolution. As for nanotube carriers, we concentrated on natural halloysite clay nanotubes as cores for LbL encapsulation that allows high drug loading and sustains its release over tens and hundreds hours. Further drug release prolongation was reached with formation of the tube-end stoppers. PMID:25450068

  9. Thermosensitive liposomes entrapping iron oxide nanoparticles for controllable drug release.

    PubMed

    Tai, Lin-Ai; Tsai, Pi-Ju; Wang, Yu-Chao; Wang, Yu-Jing; Lo, Leu-Wei; Yang, Chung-Shi

    2009-04-01

    Iron oxide nanoparticles can serve as a heating source upon alternative magnetic field (AMF) exposure. Iron oxide nanoparticles can be mixed with thermosensitive nanovehicles for hyperthermia-induced drug release, yet such a design and mechanism may not be suitable for controllable drug release applications in which the tissues are susceptible to environmental temperature change such as brain tissue. In the present study, iron oxide nanoparticles were entrapped inside of thermosensitive liposomes for AMF-induced drug release while the environmental temperature was maintained at a constant level. Carboxyfluorescein was co-entrapped with the iron oxide nanoparticles in the liposomes as a model compound for monitoring drug release and environmental temperature was maintained with a water circulator jacket. These experiments have been successfully performed in solution, in phantom and in anesthetized animals. Furthermore, the thermosensitive liposomes were administered into rat forearm skeletal muscle, and the release of carboxylfluorescein triggered by the external alternative magnetic field was monitored by an implanted microdialysis perfusion probe with an on-line laser-induced fluorescence detector. In the future such a device could be applied to simultaneous magnetic resonance imaging and non-invasive drug release in temperature-sensitive applications. PMID:19420485

  10. Diisocyanate mediated polyether modified gelatin drug carrier for controlled release

    PubMed Central

    Vijayakumar, Vediappan; Subramanian, Kaliappagounder

    2013-01-01

    Gelatin is an extensively studied biopolymer hydrogel drug carrier due to its biocompatibility, biodegradability and non-toxicity of its biodegraded products formed in vivo. But with the pristine gelatin it is difficult to achieve a controlled and desirable drug release characteristics due to its structural and thermal lability and high solubility in aqueous biofluids. Hence it is necessary to modify its solubility and structural stability in biofluids to achieve controlled release features with improved drug efficacy and broader carrier applications. In the present explorations an effort is made in this direction by cross linking gelatin to different extents using hitherto not studied isocyanate terminated poly(ether) as a macrocrosslinker prepared from poly(ethylene glycol) and isophorone diisocyanate in dimethyl sulfoxide. The crosslinked samples were analyzed for structure by Fourier transform-infrared spectroscopy, thermal behavior through thermogravimetric analysis and differential scanning calorimetry. The cross linked gelatins were biodegradable, insoluble and swellable in biofluids. They were evaluated as a carrier for in vitro drug delivery taking theophylline as a model drug used in asthma therapy. The crosslinking of gelatin decreased the drug release rate by 10–20% depending upon the extent of crosslinking. The modeled drug release characteristics revealed an anomalous transport mechanism. The release rates for ampicillin sodium, 5-fluorouracil and theophylline drugs in a typical crosslinked gelatin carrier were found to depend on the solubility and hydrophobicity of the drugs, and the pH of the fluid. The observed results indicated that this material can prove its mettle as a viable carrier matrix in drug delivery applications. PMID:24493973

  11. Drug release kinetics from carboxymethylcellulose-bacterial cellulose composite films.

    PubMed

    Juncu, Gheorghe; Stoica-Guzun, Anicuta; Stroescu, Marta; Isopencu, Gabriela; Jinga, Sorin Ion

    2016-08-30

    Composite films of sodium carboxymethyl cellulose and bacterial cellulose (NaCMC-BC) cross-linked with citric acid (CA) were prepared by solution casting method. Ibuprofen sodium salt (IbuNa) has been used to study the mechanism of drug release from composite films. Surface morphology was investigated by scanning electron microscopy (SEM) and proved that the BC content influences the aspect of the films. Fourier transformed infrared spectroscopy (FTIR) revealed specific peaks in IR spectra of composite films which sustain that NaCMC was cross-linked with CA. Starting from swelling observations, the release kinetic of IbuNa was described using a model which neglects the volume expansion due to polymer swelling and which considers non-linear diffusion coefficients for drug and solvent. The IbuNa release is also influenced by BC content, the drug release rate was decreasing with the increase of BC content. PMID:26688041

  12. Drug release from porous silicon for stable neural interface

    NASA Astrophysics Data System (ADS)

    Sun, Tao; Tsang, Wei Mong; Park, Woo-Tae

    2014-02-01

    70 μm-thick porous Si (PSi) layer with the pore size of 11.1 ± 7.6 nm was formed on an 8-in. Si wafer via an anodization process for the microfabrication of a microelectrode to record neural signals. To reduce host tissue responses to the microelectrode and achieve a stable neural interface, water-soluble dexamethesone (Dex) was loaded into the PSi via incubation with the drug solution overnight. After the drug loading process, the pore size of PSi reduced to 4.7 ± 2.6 nm on the basis of scanning electron microscopic (SEM) images, while its wettability was remarkably enhanced. Fluorescence images demonstrated that Dex was loaded into the porous structure of the PSi. Degradation rate of the PSi was investigated by incubation in distilled water for 21 days. Moreover, the drug release profile of the Dex-loaded PSi was a combination of an initial burst release and subsequent sustained release. To evaluate cellular responses to the drug release from the PSi, primary astrocytes were seeded on the surface of samples. After 2 days of culture, the Dex-loaded PSi could not only moderately prevent astrocyte adhesion in comparison with Si, but also more effectively suppress the activation of primary astrocytes than unloaded PSi due to the drug release. Therefore, it might be an effective method to reduce host tissue responses and stabilize the quality of the recorded neural signal by means of loading drugs into the PSi component of the microelectrode.

  13. Release mechanism and parameter estimation in drug-eluting stent systems: analytical solutions of drug release and tissue transport

    PubMed Central

    McGinty, Sean; McKee, Sean; McCormick, Christopher; Wheel, Marcus

    2015-01-01

    Drug-eluting stents have significantly improved the treatment of coronary artery disease. They offer reduced rates of restenosis compared with their bare-metal predecessors and are the current gold standard in percutaneous coronary interventions. Drug-eluting stents have been approved for use in humans since 2002 and yet, despite the intensive research activity over the past decade, the drug release mechanism(s) and the uptake into the arterial wall are still poorly understood. While stent manufacturers have focussed primarily on empirical methods, several mathematical models have appeared in the literature considering the release problem, the uptake problem and also the coupled problem. However, two significant challenges that remain are in understanding the drug release mechanism(s) and also the determination of the various parameters characterizing the system. These include drug diffusion coefficients and dissolution constants in the stent polymer coating as well as drug diffusion coefficients, binding/uptake rates and the magnitude of the transmural convection in the arterial wall. In this paper we attempt to address these problems. We provide analytical solutions which, when compared with appropriate experiments, may allow the various parameters of the system to be estimated via the inverse problem. The analytical solutions which we provide here for drug release in vitro may thus be used as a tool for providing insights into the mechanism(s) of release. PMID:24463960

  14. Formation of drug/surfactant catanionic vesicles and their application in sustained drug release.

    PubMed

    Jiang, Yue; Li, Feifei; Luan, Yuxia; Cao, Wenting; Ji, Xiaoqing; Zhao, Lanxia; Zhang, Longlong; Li, Zhonghao

    2012-10-15

    The aggregation behavior of the cationic drug/anionic surfactant vesicles formed by tetracaine hydrochloride (TH) and double-chain surfactant, sodium bis(2-ethylhexyl)sulfosuccinate (AOT), was investigated. By controlling the molar ratio of TH to AOT, a transition from catanionic vesicles to micelles was observed. The catanionic aggregates exhibited different charge properties, structures, interaction enthalpies and drug release behaviors depending on the composition. To characterize the cationic drug/anionic surfactant system, transmission electron microscopy (TEM), dynamic light scattering (DLS), isothermal titration calorimetry (ITC), conductivity, turbidity and zeta potential (ζ) measurements were performed. The drug release results indicate that the present drug-containing catanionic vesicles have promising applications in drug delivery systems. Furthermore, the percentage of drug distributed in the catanionic vesicles or micelles can be obtained by comparing the cumulative release of the corresponding aggregates with the pure drug solution. PMID:22871561

  15. Controlled release of dual drugs from emulsion electrospun nanofibrous mats.

    PubMed

    Yan, Su; Xiaoqiang, Li; Shuiping, Liu; Xiumei, Mo; Ramakrishna, Seeram

    2009-10-15

    The purpose of this work is to develop a novel type of tissue engineering scaffold or drugs delivery carrier with the capability of encapsulation and controlled release drugs. In this study, Rhodamine B and Bovine Serum Albumin (BSA) were successfully incorporated into nanofibers by means of emulsion electrospinning. The morphology of composite nanofibers was studied by Scanning Electron Microscopy (SEM). The composite nanofibrous mats made from emulsion electrospinning were characterized by water contact angle measurement and X-ray diffraction. In vitro dual drugs release behaviors from composite nanofibrous mats were investigated. The results indicated that the incorporated drug and/or proteins in composite fibrous mats made from electrospinning could be control released by adjusting the processes of emulsions preparation. PMID:19586756

  16. Triggering of drug release of particles in hair follicles.

    PubMed

    Mak, Wing Cheung; Patzelt, Alexa; Richter, Heike; Renneberg, Reinhardt; Lai, Kwok Kei; Rühl, Eckart; Sterry, Wolfram; Lademann, Jürgen

    2012-06-28

    Particulate drug delivery via hair follicles represents a promising concept, although requirements are high. This process must be realized at the desired depth and at the appropriate time, due to the fact that the particles themselves are not able to overcome the follicular skin barrier. In the present study, a novel triggering concept for the release of a model drug from the delivering particles is presented based on the application of two different particle types of the same size, where one particle type is the drug carrier, and the second one is loaded with a protease. The latter particle type is supposed to interact with the drug-carrying particles to trigger the drug release. A mixture of both particles was applied onto porcine skin samples, followed by follicular analysis. As a control, the particles were applied unaided without protease, whereas one skin area remained untreated. The investigations revealed that the protease was able to release the model drug from the delivering particles in significant depths within the hair follicle (866±62nm). Additionally, an uptake of the model drug in the sebaceous gland was observed after release providing a promising novel approach for the development of treatment strategies for different skin diseases. PMID:22516090

  17. Gravity spun polycaprolactone fibres: controlling release of a hydrophilic macromolecule (ovalbumin) and a lipophilic drug (progesterone).

    PubMed

    Williamson, Matthew R; Chang, Hsin-I; Coombes, Allan G A

    2004-09-01

    A hydrophilic macromolecule (ovalbumin (OVA)) and a lipophilic drug (progesterone) were incorporated in polycaprolactone (PCL) fibres by gravity spinning using particulate dispersions and co-solutions of PCL and steroid, respectively. PCL fibres loaded with 1% (w/w) OVA powder displayed a pronounced burst release phase (60% of the protein load) over 2 days in PBS at 37 degrees C. The release profile then tended to plateau. In contrast, OVA nanoparticle-loaded fibres exhibited delayed protein release initially and then a major increase at day 14. This behaviour may be useful for sequential release of polypeptide growth factors which are influential at specific time points in the wound healing process. SDS-PAGE analysis revealed that the protein molecular weight was conserved during fibre spinning. The amount of progesterone release from PCL fibres in PBS increased with drug loading but the cumulative release profiles (% w/w) were little affected by the initial drug loading of the fibres (1.5 and 3.5% w/w) or the concentration of the PCL spinning solution (12.5 and 20% w/v). Steroid delivery was rapid due to the high fibre surface area and high permeability of PCL resulting in complete drug loss over 24h. Released progesterone inhibited the growth of MCF-7 breast epithelial cells in culture, demonstrating retention of bioactivity. Gravity spinning shows potential for producing PCL fibre-based platforms for programmed delivery of bioactive molecules of utility for tissue engineering and drug delivery. PMID:15109868

  18. Incorporating small molecules or biologics into nanofibers for optimized drug release: A review.

    PubMed

    Sebe, István; Szabó, Péter; Kállai-Szabó, Barnabás; Zelkó, Romána

    2015-10-15

    Over the past several decades, the formulation of novel nanofiber-based drug delivery systems focusing on specific delivery purposes has been investigated worldwide with a continuous level of interest. The unique structure and properties of nanoscale fibrous systems, such as their high specific-area-to-volume ratio and high porosity and the possibility of controlling their crystalline-amorphous phase transitions, make them a desirable formulation pathway to satisfy the needs of recent pharmaceutical development. Fibrous delivery systems can facilitate the accelerated dissolution and increased solubility of small molecules and can also be useful in controlling drug delivery over time (for local or systemic drug administration). In the latter case, the release periods can be tuned over a wide range (from hours to weeks), e.g., by adjusting the fiber diameter and selecting the appropriate polymers. The solubility of the polymer, the fiber diameter and the fiber structure are the primary parameters affecting drug release. In addition to immediate and sustained release, other release profiles, such as biphasic release, can also be achieved. Chemical conjugation and surface functionalization offer further possibilities for the control of drug release. In the case of small molecules, developments focus mostly on overcoming the unfavorable physicochemical nature of the active agents. By contrast, in the preparation of macromolecule-loaded nanofibers, maximizing the biological activity of the macromolecules presents the greatest challenge. The authors' intent is to provide a comprehensive overview of the key parameters of advanced drug delivery systems of this type. PMID:26307263

  19. Dual-drug encapsulation and release from core-shell nanofibers.

    PubMed

    Su, Yan; Su, Qianqian; Liu, Wei; Jin, Guori; Mo, Xiumei; Ramakrishn, Seeram

    2012-01-01

    The purpose of this work was to develop a type of tissue-engineering scaffold or drug-delivery carrier with the capability of encapsulation and controlled release of dual drugs. In this study, Rhodamine B and bovine serum albumin (BSA) were successfully incorporated into nanofibers by means of blending or coaxial electrospinning. The morphology of composite nanofibers was studied by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The composite nanofibrous mats made from coaxial electrospinning were characterized by X-ray diffraction. In vitro dual-drug release behaviors from composite nanofibrous mats were investigated. From the drug-release profiles, it shows that the location where the drug or protein is put into (into the core or shell of the nanofibers) can affect the drug-release profile in the coaxially electrospun fibers. The results imply that the drug- and/or protein-release profile in composite fibrous mats made from electrospinning can be controlled by altering the coaxial electrospinning process and has significant implications for a wide range of applications such as tissue regeneration, combined therapies or even cancer treatments. PMID:21418751

  20. An investigation of effects of modification processes on physical properties and mechanism of drug release for sustaining drug release from modified rice.

    PubMed

    Ngo, Vuong Duy; Luu, Thinh Duc; Van Vo, Toi; Tran, Van-Thanh; Duan, Wei; Tran, Phuong Ha-Lien; Tran, Thao Truong-Dinh

    2016-10-01

    The aim of this study was to investigate the effect of modification processes on physical properties and explain the mechanism of sustained drug release from modified rice (MR). Various types of Vietnamese rice were introduced in the study as the matrices of sustained release dosage form. Rice was thermally modified in water for a determined temperature at different times with a simple process. Then tablets containing MR and isradipine, the model drug, were prepared to investigate the capability of sustained drug release. Scanning electron microscopy (SEM) was used to determine different morphologies between MR formulations. Flow property of MR was analyzed by Hausner ratio and Carr's indices. The dissolution rate and swelling/erosion behaviors of tablets were evaluated at pH 1.2 and pH6.8 at 37±0.5°C. The matrix tablet containing MR showed a sustained release as compared to the control. The SEM analyses and swelling/erosion studies indicated that the morphology as well as swelling/erosion rate of MR were modulated by modification time, drying method and incubation. It was found that the modification process was crucial because it could highly affect the granule morphologies and hence, leading to the change of flowability and swelling/erosion capacity for sustained release of drug. PMID:27287092

  1. Binding and release of drugs into and from thermosensitive poly(N-vinyl caprolactam) nanoparticles.

    PubMed

    Vihola, Henna; Laukkanen, Antti; Hirvonen, Jouni; Tenhu, Heikki

    2002-07-01

    Three model drug substances, the beta-blocking agents nadolol and propranolol and a choline-esterase inhibitor tacrine, were used in order to determine how different drug molecules affect the behavior of thermally responsive polymer nanoparticles composed of poly(N-vinylcaprolactam) (PVCL). Pure PVCL particles in water exist in a swollen state at room temperature, but the size of the particles decreases discontinuously when the temperature is raised above the volume phase transition temperature. At temperatures above this transition temperature, water is expelled out from the nanoscopic hydrogel particles. Light scattering studies revealed that the more hydrophobic drug substances, propranolol and tacrine, considerably swell the PVCL-microgel. The more hydrophilic drug, nadolol, decreased the transition temperature of PVCL particles, whereas the transition temperature values of pure PVCL particles and that of the added propranolol and tacrine were quite similar. Attenuated drug release results showed that the beta-blocking agents were tightly bound to the microgel, and this was more evident at higher temperatures. On the contrary, the release of tacrine across the cellulose membrane was increased when PVCL particles were present. Thus, both physical and chemical properties of the drugs clearly affected their binding to PVCL particles and the release of drugs was affected by the temperature. PMID:12113893

  2. Controlled Release for Local Delivery of Drugs: Barriers and Models

    PubMed Central

    Weiser, Jennifer R.; Saltzman, W. Mark

    2014-01-01

    Controlled release systems are an effective means for local drug delivery. In local drug delivery, the major goal is to supply therapeutic levels of a drug agent at a physical site in the body for a prolonged period. A second goal is to reduce systemic toxicities, by avoiding the delivery of agents to non-target tissues remote from the site. Understanding the dynamics of drug transport in the vicinity of a local drug delivery device is helpful in achieving both of these goals. Here, we provide an overview of controlled release systems for local delivery and we review mathematical models of drug transport in tissue, which describe the local penetration of drugs into tissue and illustrate the factors—such as diffusion, convection, and elimination—that control drug dispersion and its ultimate fate. This review highlights the important role of controlled release science in development of reliable methods for local delivery, as well as the barriers to accomplishing effective delivery in the brain, blood vessels, mucosal epithelia, and the skin. PMID:24801251

  3. Effect of geometry on drug release from 3D printed tablets.

    PubMed

    Goyanes, Alvaro; Robles Martinez, Pamela; Buanz, Asma; Basit, Abdul W; Gaisford, Simon

    2015-10-30

    The aim of this work was to explore the feasibility of combining hot melt extrusion (HME) with 3D printing (3DP) technology, with a view to producing different shaped tablets which would be otherwise difficult to produce using traditional methods. A filament extruder was used to obtain approx. 4% paracetamol loaded filaments of polyvinyl alcohol with characteristics suitable for use in fused-deposition modelling 3DP. Five different tablet geometries were successfully 3D-printed-cube, pyramid, cylinder, sphere and torus. The printing process did not affect the stability of the drug. Drug release from the tablets was not dependent on the surface area but instead on surface area to volume ratio, indicating the influence that geometrical shape has on drug release. An erosion-mediated process controlled drug release. This work has demonstrated the potential of 3DP to manufacture tablet shapes of different geometries, many of which would be challenging to manufacture by powder compaction. PMID:25934428

  4. Pediatric drug formulation of sodium benzoate extended-release granules.

    PubMed

    Combescot, E; Morat, G; de Lonlay, P; Boudy, V

    2016-01-01

    Urea cycle disorders are a group of inherited orphan diseases leading to hyperammonemia. Current therapeutic strategy includes high doses of sodium benzoate leading to three or four oral intakes per day. As this drug is currently available in capsules or in solution, children are either unable to swallow the capsule or reluctant to take the drug due to its strong bitter taste. The objective of the present study was to develop solid, multiparticulate formulations of sodium benzoate, which are suitable for pediatric patients (i.e. flavor-masked, easy to swallow and with a dosing system). Drug layering and coating in a fluidized bed were applied for preparing sustained-release granules. Two types of inert cores (GalenIQ® and Suglets®) and three different polymers (Kollicoat®, Aquacoat® and Eudragit®) were tested in order to select the most appropriate polymer and starter core for our purpose. Physical characteristics and drug release profiles of the pellets were evaluated. A Suglets® core associated with a Kollicoat® coating seems to be the best combination for an extended release of sodium benzoate. A curing period of 8 h was necessary to complete film formation and the resulting drug release pattern was found to be dependent of the acidity of the release medium. PMID:25582668

  5. Continuous Drug Release by Sea Anemone Nematostella vectensis Stinging Microcapsules

    PubMed Central

    Tal, Yossi; Ayalon, Ari; Sharaev, Agnesa; Kazir, Zoya; Brekhman, Vera; Lotan, Tamar

    2014-01-01

    Transdermal delivery is an attractive option for drug delivery. Nevertheless, the skin is a tough barrier and only a limited number of drugs can be delivered through it. The most difficult to deliver are hydrophilic drugs. The stinging mechanism of the cnidarians is a sophisticated injection system consisting of microcapsular nematocysts, which utilize built-in high osmotic pressures to inject a submicron tubule that penetrates and delivers their contents to the prey. Here we show, for the first time, that the nematocysts of the starlet sea anemone Nematostella vectensis can be isolated and incorporated into a topical formulation for continuous drug delivery. We demonstrate quantitative delivery of nicotinamide and lidocaine hydrochloride as a function of microcapsular dose or drug exposure. We also show how the released submicron tubules can be exploited as a skin penetration enhancer prior to and independently of drug application. The microcapsules are non-irritant and may offer an attractive alternative for hydrophilic transdermal drug delivery. PMID:24473172

  6. Continuous drug release by sea anemone Nematostella vectensis stinging microcapsules.

    PubMed

    Tal, Yossi; Ayalon, Ari; Sharaev, Agnesa; Kazir, Zoya; Brekhman, Vera; Lotan, Tamar

    2014-02-01

    Transdermal delivery is an attractive option for drug delivery. Nevertheless, the skin is a tough barrier and only a limited number of drugs can be delivered through it. The most difficult to deliver are hydrophilic drugs. The stinging mechanism of the cnidarians is a sophisticated injection system consisting of microcapsular nematocysts, which utilize built-in high osmotic pressures to inject a submicron tubule that penetrates and delivers their contents to the prey. Here we show, for the first time, that the nematocysts of the starlet sea anemone Nematostella vectensis can be isolated and incorporated into a topical formulation for continuous drug delivery. We demonstrate quantitative delivery of nicotinamide and lidocaine hydrochloride as a function of microcapsular dose or drug exposure. We also show how the released submicron tubules can be exploited as a skin penetration enhancer prior to and independently of drug application. The microcapsules are non-irritant and may offer an attractive alternative for hydrophilic transdermal drug delivery. PMID:24473172

  7. Sol-gel encapsulation for controlled drug release and biosensing

    NASA Astrophysics Data System (ADS)

    Fang, Jonathan

    The main focus of this dissertation is to investigate the use of sol-gel encapsulation of biomolecules for controlled drug release and biosensing. Controlled drug release has advantages over conventional therapies in that it maintains a constant, therapeutic drug level in the body for prolonged periods of time. The anti-hypertensive drug Captopril was encapsulated in sol-gel materials of various forms, such as silica xerogels and nanoparticles. The primary objective was to show that sol-gel silica materials are promising drug carriers for controlled release by releasing Captopril at a release rate that is within a therapeutic range. We were able to demonstrate desired release for over a week from Captopril-doped silica xerogels and overall release from Captopril-doped silica nanoparticles. As an aside, the antibiotic Vancomycin was also encapsulated in these porous silica nanoparticles and desired release was obtained for several days in-vitro. The second part of the dissertation focuses on immobilizing antibodies and proteins in sol-gel to detect various analytes, such as hormones and amino acids. Sol-gel competitive immunoassays on antibody-doped silica xerogels were used for hormone detection. Calibration for insulin and C-peptide in standard solutions was obtained in the nM range. In addition, NASA-Ames is also interested in developing a reagentless biosensor using bacterial periplasmic binding proteins (bPBPs) to detect specific biomarkers, such as amino acids and phosphate. These bPBPs were doubly labeled with two different fluorophores and encapsulated in silica xerogels. Ligand-binding experiments were performed on the bPBPs in solution and in sol-gel. Ligand-binding was monitored by fluorescence resonance energy transfer (FRET) between the two fluorophores on the bPBP. Titration data show that one bPBP has retained its ligand-binding properties in sol-gel.

  8. Drug Convictions May Affect Your Student Aid.

    ERIC Educational Resources Information Center

    Department of Education, Washington, DC.

    This booklet explains problems posed by prior drug convictions to college-bound students seeking federal financial aid. Under a new law which takes effect on July 1, 2000, some students who have drug convictions may be ineligible for federal student aid. For possession of illegal drugs, students are ineligible from the date of conviction for one…

  9. Development of novel small molecules for imaging and drug release

    NASA Astrophysics Data System (ADS)

    Cao, Yanting

    Small organic molecules, including small molecule based fluorescent probes, small molecule based drugs or prodrugs, and smart multifunctional fluorescent drug delivery systems play important roles in biological research, drug discovery, and clinical practices. Despite the significant progress made in these fields, the development of novel and diverse small molecules is needed to meet various demands for research and clinical applications. My Ph.D study focuses on the development of novel functional molecules for recognition, imaging and drug release. In the first part, a turn-on fluorescent probe is developed for the detection of intracellular adenosine-5'-triphosphate (ATP) levels based on multiplexing recognitions. Considering the unique and complicated structure of ATP molecules, a fluorescent probe has been implemented with improved sensitivity and selectivity due to two synergistic binding recognitions by incorporating of 2, 2'-dipicolylamine (Dpa)-Zn(II) for targeting of phospho anions and phenylboronic acid group for cis-diol moiety. The novel probe is able to detect intracellular ATP levels in SH-SY5Y cells. Meanwhile, the advantages of multiplexing recognition design concept have been demonstrated using two control molecules. In the second part, a prodrug system is developed to deliver multiple drugs within one small molecule entity. The prodrug is designed by using 1-(2-nitrophenyl)ethyl (NPE) as phototrigger, and biphenol biquaternary ammonium as the prodrug. With controlled photo activation, both DNA cross-linking agents mechlorethamine and o-quinone methide are delivered and released at the preferred site, leading to efficient DNA cross-links formation and cell death. The prodrug shows negligible cytotoxicity towards normal skin cells (Hekn cells) with and without UV activation, but displays potent activity towards cancer cells (HeLa cells) upon UV activation. The multiple drug release system may hold a great potential for practical application. In the

  10. Composite chitosan hydrogels for extended release of hydrophobic drugs.

    PubMed

    Delmar, Keren; Bianco-Peled, Havazelet

    2016-01-20

    A composite chitosan hydrogel durable in physiological conditions intended for sustained release of hydrophobic drugs was investigated. The design is based on chitosan crosslinked with genipin with embedded biocompatible non-ionic microemulsion (ME). A prolonged release period of 48 h in water, and of 24h in phosphate buffer saline (PBS) of pH 7.4 was demonstrated for Nile red and curcumin. The differences in release patterns in water and PBS were attributed to distinct dissimilarities in the swelling behaviors; in water, the hydrogels swell enormously, while in PBS they expel water and shrink. The release mechanism dominating this system is complex due to intermolecular bonding between the oil droplets and the polymeric network, as confirmed by Fourier transform infrared spectroscopy (FTIR) experiments. This is the first time that oil in water microemulsions were introduced into a chitosan hydrogels for the creation of a hydrophobic drug delivery system. PMID:26572389

  11. Analyzing the impact of different excipients on drug release behavior in hot-melt extrusion formulations using FTIR spectroscopic imaging.

    PubMed

    Pudlas, Marieke; Kyeremateng, Samuel O; Williams, Leonardo A M; Kimber, James A; van Lishaut, Holger; Kazarian, Sergei G; Woehrle, Gerd H

    2015-01-25

    The drug release performance of hot-melt extrudate formulations is mainly affected by its composition and interactions between excipients, drug and the dissolution media. For targeted formulation development, it is crucial to understand the role of these interactions on the drug release performance of extrudate formulations. Attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopic imaging was used with an in-situ flow-cell device to analyze the impact of different excipients on drug release from extrudates. The compositions differed in the type of polymer (copovidone and Soluplus®), the salt or acid form of ibuprofen and the addition of sodium carbonate. For comparison, conventional USP (United States Pharmacopeia) Apparatus 2 dissolution studies were performed. FTIR imaging revealed that differences in the drug release rate were mainly due to drug-polymer interactions. Ibuprofen acid showed interactions with the matrix polymer and exhibited a slower drug release compared to non-interacting ibuprofen salt. Addition of sodium carbonate to the ibuprofen acid containing formulations enhanced the drug release rate of these systems by interfering with the drug-polymer interactions. In addition, drug release rates also depended on the polymer type, showing faster drug release rates for extrudate formulations containing copovidone compared to Soluplus®. FTIR imaging revealed that the stronger the drug-polymer interaction in the formulations, the slower the drug release. The addition of sodium carbonate improved release as it reduces drug-polymer interactions and allows for the formation of the more water-soluble ibuprofen salt. PMID:25445833

  12. Current strategies for sustaining drug release from electrospun nanofibers.

    PubMed

    Chou, Shih-Feng; Carson, Daniel; Woodrow, Kim A

    2015-12-28

    Electrospun drug-eluting fibers are emerging as a novel dosage form for multipurpose prevention against sexually transmitted infections, including HIV, and unintended pregnancy. Previous work from our lab and others show the versatility of this platform to deliver large doses of physico-chemically diverse agents. However, there is still an unmet need to develop practical fiber formulations for water-soluble small molecule drugs needed at high dosing due to intrinsic low potency or desire for sustained prevention. To date, most sustained release fibers have been restricted to the delivery of biologics or hydrophobic small molecules at low drug loading of typically <1 wt.%, which is often impractical for most clinical applications. For hydrophilic small molecule drugs, their high aqueous solubility and poor partitioning and incompatibility with insoluble polymers make long-term release even more challenging. Here we investigate several existing strategies to sustain release of hydrophilic small molecule drugs that are highly-loaded in electrospun fibers. In particular, we investigate what is known about the design constraints required to realize multi-day release from fibers fabricated from uniaxial and coaxial electrospinning. PMID:26363300

  13. Transdermal Delivery Devices: Fabrication, Mechanics and Drug Release from Silk**

    PubMed Central

    Raja, Waseem K.; MacCorkle, Scott; Diwan, Izzuddin M.; Abdurrob, Abdurrahman; Lu, Jessica; Omenetto, Fiorenzo G.; Kaplan, David L.

    2013-01-01

    Microneedles are a relatively simple, minimally invasive and painless approach to deliver drugs across the skin. However, there remain limitations with this approach because of the materials most commonly utilized for such systems. Silk protein, with tunable and biocompatibility properties, is a useful biomaterial to overcome the current limitations with microneedles. Silk devices preserve drug activity, offer superior mechanical properties and biocompatibility, can be tuned for biodegradability, and can be processed under aqueous, benign conditions. In the present work, we report the fabrication of dense microneedle arrays from silk with different drug release kinetics. The mechanical properties of the microneedle patches are tuned by post-fabrication treatments or by loading the needles with silk microparticles to increase capacity and mechanical strength. Drug release is further enhanced by the encapsulation of the drugs in the silk matrix and coating with a thin dissolvable drug layer. The microneedles are used on human cadaver skin and drugs were delivered successfully. The various attributes demonstrated suggest that silk-based microneedle devices can provide significant benefit as a platform material for transdermal drug delivery. PMID:23653252

  14. Organically modified titania nanoparticles for sustained drug release applications.

    PubMed

    Sethi, Komal; Roy, Indrajit

    2015-10-15

    In this paper, we report the synthesis, characterization of drug-doped organically modified titania nanoparticles, and their applications in sustained drug release. The drug-doped nanoparticles were synthesized in the hydrophobic core of oil-in-water microemulsion medium. Structural aspects obtained through TEM and FESEM depicted that organically modified titania nanoparticles are monodispersed with spherical morphology, with an average size of around 200 nm. Their polymorphic forms and porosity were determined using powder XRD and BET, respectively, which showed that they are present in the anatase form, with a surface area of 136.5 m(2)/g and pore-diameter of 5.23 nm. After synthesis and basic structural characterizations, optical properties were studied for both fluorophore and drug encapsulated nanoparticles. The results showed that though the optical properties of the fluorophore are partially diminished upon nanoencapsulation, it became more stable against chemical quenching. The nanoparticles showed pH-dependent drug release pattern. In vitro studies showed that the nanoparticles were efficiently uptaken by cells. Cell viability assay results showed that though the placebo nanoparticles are non-cytotoxic, the drug-doped nanoparticles show drug-induced toxicity. Therefore, such porous nanoparticles can be used in non-toxic drug delivery applications. PMID:26093234

  15. Application of a binary polymer system in drug release rate modulation. 1. Characterization of release mechanism.

    PubMed

    Kim, H; Fassihi, R

    1997-03-01

    A new binary polymer matrix tablet for oral administration was developed. The system will deliver drug at variable rates according to zero-order kinetics for total drug content and is manufactured by direct compression technology. Highly methoxylated pectin and hydroxypropyl methylcellulose (HPMC) at different ratios were used as major formulation components, and prednisolone was used as the drug model. The results indicate that by increasing pectin:HPMC ratios, release rates are increased, but zero-order kinetics prevail throughout the dissolution period (e.g., 3-22 h). Different pectin:HPMC ratios provide a range of viscosities that modulates drug release and results in rapid hydration/gelation in both axial and radial directions, as evidenced by photomicrographic pictures. This hydration-gelation contributes to the development of swelling/erosion boundaries and consequently to constant drug release. Combination of these particular polymers facilitates rapid formation of necessary boundaries (i.e., gel layer and solid core boundaries) to control overall mass transfer processes. The drug fraction released (Mt/M infinity), release kinetics, and mechanism of release were analyzed by applying the simple power law expression Mt/M infinity = kt(n), where k is a kinetic constant and the exponent n is indicative of the release mechanism. The calculated n values for pectin:HPMC ratios of 4:5, 3:6, and 2:7 were >0.95, which is indicative of a Case II transport mechanism (polymer relaxation/dissolution). The achievement of total zero-order kinetics is due to the predictable swelling/erosion and final polymer chain deaggregation and dissolution that is regulated by the gelling characteristics of polymers in the formulation. PMID:9050799

  16. Fractal kinetics in drug release from finite fractal matrices

    NASA Astrophysics Data System (ADS)

    Kosmidis, Kosmas; Argyrakis, Panos; Macheras, Panos

    2003-09-01

    We have re-examined the random release of particles from fractal polymer matrices using Monte Carlo simulations, a problem originally studied by Bunde et al. [J. Chem. Phys. 83, 5909 (1985)]. A certain population of particles diffuses on a fractal structure, and as particles reach the boundaries of the structure they are removed from the system. We find that the number of particles that escape from the matrix as a function of time can be approximated by a Weibull (stretched exponential) function, similar to the case of release from Euclidean matrices. The earlier result that fractal release rates are described by power laws is correct only at the initial stage of the release, but it has to be modified if one is to describe in one picture the entire process for a finite system. These results pertain to the release of drugs, chemicals, agrochemicals, etc., from delivery systems.

  17. Cellulose, Chitosan, and Keratin Composite Materials. Controlled Drug Release

    PubMed Central

    2015-01-01

    A method was developed in which cellulose (CEL) and/or chitosan (CS) were added to keratin (KER) to enable [CEL/CS+KER] composites to have better mechanical strength and wider utilization. Butylmethylimmidazolium chloride ([BMIm+Cl–]), an ionic liquid, was used as the sole solvent, and because the [BMIm+Cl–] used was recovered, the method is green and recyclable. Fourier transform infrared spectroscopy results confirm that KER, CS, and CEL remain chemically intact in the composites. Tensile strength results expectedly show that adding CEL or CS into KER substantially increases the mechanical strength of the composites. We found that CEL, CS, and KER can encapsulate drugs such as ciprofloxacin (CPX) and then release the drug either as a single or as two- or three-component composites. Interestingly, release rates of CPX by CEL and CS either as a single or as [CEL+CS] composite are faster and independent of concentration of CS and CEL. Conversely, the release rate by KER is much slower, and when incorporated into CEL, CS, or CEL+CS, it substantially slows the rate as well. Furthermore, the reducing rate was found to correlate with the concentration of KER in the composites. KER, a protein, is known to have secondary structure, whereas CEL and CS exist only in random form. This makes KER structurally denser than CEL and CS; hence, KER releases the drug slower than CEL and CS. The results clearly indicate that drug release can be controlled and adjusted at any rate by judiciously selecting the concentration of KER in the composites. Furthermore, the fact that the [CEL+CS+KER] composite has combined properties of its components, namely, superior mechanical strength (CEL), hemostasis and bactericide (CS), and controlled drug release (KER), indicates that this novel composite can be used in ways which hitherto were not possible, e.g., as a high-performance bandage to treat chronic and ulcerous wounds. PMID:25548871

  18. Microfluidic Synthesis of pH-Sensitive Multicompartmental Microparticles for Multimodulated Drug Release.

    PubMed

    Kim, Hyeon Ung; Choi, Dae Gun; Roh, Yoon Ho; Shim, Min Suk; Bong, Ki Wan

    2016-07-01

    Stimuli-responsive carriers releasing multiple drugs have been researched for synergistic combinatorial cancer treatment with reduced side-effects. However, previously used drug carriers have limitations in encapsulating multiple drug components in a single carrier and releasing each drug independently. In this work, pH-sensitive, multimodulated, anisotropic drug carrier particles are synthesized using an acid-cleavable polymer and stop-flow lithography. The particles exhibit a faster drug release rate at the acidic pH of tumors than at physiological pH, demonstrating their potential for tumor-selective drug release. The drug release rate of the particles can be adjusted by controlling the monomer composition. To accomplish multimodulated drug release, multicompartmental particles are synthesized. The drug release profile of each compartment is programmed by tailoring the monomer composition. These pH-sensitive, multicompartmental particles are promising drug carriers enabling tumor-selective and multimodulated release of multiple drugs for synergistic combination cancer therapy. PMID:27197594

  19. Drug release from hydrazone-containing peptide amphiphiles.

    PubMed

    Matson, John B; Stupp, Samuel I

    2011-07-28

    Hydrolytically-labile hydrazones in peptide amphiphiles were studied as degradable tethers for release of the drug nabumetone from nanofiber gels. On-resin addition of the novel compound tri-Boc-hydrazido adipic acid to a lysine ε-amine allowed for precise placement of a hydrazide in a peptide sequence. PMID:21674107

  20. Drug release from hydrazone-containing peptide amphiphiles

    SciTech Connect

    Matson, John B.; Stupp, Samuel I.

    2012-03-15

    Hydrolytically-labile hydrazones in peptide amphiphiles were studied as degradable tethers for release of the drug nabumetone from nanofiber gels. On-resin addition of the novel compound tri-Boc-hydrazido adipic acid to a lysine E-amine allowed for precise placement of a hydrazide in a peptide sequence.

  1. The effect of polymer properties on direct compression and drug release from water-insoluble controlled release matrix tablets.

    PubMed

    Grund, Julia; Koerber, Martin; Walther, Mathias; Bodmeier, Roland

    2014-07-20

    The objective of this study was to identify and evaluate key polymer properties affecting direct compression and drug release from water-insoluble matrices. Commonly used polymers, such as Kollidon(®) SR, Eudragit(®) RS and ethyl cellulose, were characterized, formulated into tablets and compared with regard to their properties in dry and wet state. A similar site percolation threshold of 65% v/v was found for all polymers in dry state. Key parameters influencing polymer compactibility were the surface properties and the glass transition temperature (T(g)), affecting polymer elasticity and particle size-dependent binding. The important properties observed in dry state also governed matrix characteristics and therefore drug release in wet state. A low T(g) (Kollidon(®) SRrelease retardation was observed in the same order as matrix integrity (Eudragit(®) RSrelease matrix systems. PMID:24746409

  2. Hollow mesoporous silica as a high drug loading carrier for regulation insoluble drug release.

    PubMed

    Geng, Hongjian; Zhao, Yating; Liu, Jia; Cui, Yu; Wang, Ying; Zhao, Qinfu; Wang, Siling

    2016-08-20

    The purpose of this study was to develop a high drug loading hollow mesoporous silica nanoparticles (HMS) and apply for regulation insoluble drug release. HMS was synthesized using hard template phenolic resin nanoparticles with the aid of cetyltrimethyl ammonium bromide (CTAB), which was simple and inexpensive. To compare the difference between normal mesoporous silica (NMS) and hollow mesoporous silica in drug loading efficiency, drug release behavior and solid state, NMS was also prepared by soft template method. Transmission electron microscopy (TEM), specific surface area analysis, FT-IR and zeta potential were employed to characterize the morphology structure and physicochemical property of these carriers. The insoluble drugs, carvedilol and fenofibrate(Car and Fen), were chosen as the model drug to be loaded into HMS and NMS. We also chose methylene blue (MB) as a basic dye to estimate the adsorption ability of these carriers from macroscopic and microscopic view, and the drug-loaded carriers were systematically studied by differential scanning calorimetry (DSC), X-ray diffraction (XRD) and UV-vis spectrophotometry. What' more, the in vivo process of HMS was also study by confocal microscopy and in vivo fluorescence imaging. In order to confirm the gastrointestinal safety of HMS, the pathological examination of stomach and intestine also be evaluated. HMS allowed a higher drug loading than NMS and exhibited a relative sustained release curve, while NMS was immediate-release. And the effect of preventing drugs crystallization was weaker than NMS. As for in vivo process, HMS was cleared relatively rapidly from the mouse gastrointestinal and barely uptake by intestinal epithelial cell in this study due to its large particle size. And the damage of HMS to gastrointestinal could be ignored. This study provided a simple method to obtain high drug loading and regulation insoluble drug release, expanded the application of inorganic carriers in drug delivery system

  3. Piroxicam loaded alginate beads obtained by prilling/microwave tandem technique: morphology and drug release.

    PubMed

    Aquino, Rita P; Auriemma, Giulia; d'Amore, Matteo; D'Ursi, Anna Maria; Mencherini, Teresa; Del Gaudio, Pasquale

    2012-07-01

    This paper presents a tandem technique, based on the combination of prilling and microwave (MW) assisted treatments, to produce biodegradable alginate carriers of piroxicam with different drug controlled release behaviours. Results showed that alginate/piroxicam beads demonstrated high encapsulation efficiency and very narrow dimensional distribution. Beads dried by MW retained shape and size distribution of the hydrated particles while drying rate was strongly increased compared to convective drying processes. Moreover, different MW irradiation regimes promoted interactions between the drug and alginate matrix, affected drug polymorphism as well as inner and surface matrix structure leading to different piroxicam release profiles. High level MW irradiation led to beads with highly porous and swellable matrix able to release piroxicam in few minutes in the intestine while convective drying produced gastro-resistant beads that exhibit sustained piroxicam release (total release in 5.5h) in intestinal environment. On these results the tandem technique prilling/MW irradiation appears to be promising to obtain alginate carrier with tailored NSAIDs release depending on drug characteristics and MW irradiation. PMID:24750857

  4. Graphene as a photothermal switch for controlled drug release

    NASA Astrophysics Data System (ADS)

    Matteini, Paolo; Tatini, Francesca; Cavigli, Lucia; Ottaviano, Stefania; Ghini, Giacomo; Pini, Roberto

    2014-06-01

    Graphene has recently emerged as a novel material in the biomedical field owing to its optical properties, biocompatibility, large specific surface area and low cost. In this paper, we provide the first demonstration of the possibility of using light to remotely trigger the release of drugs from graphene in a highly controlled manner. Different drugs including chemotherapeutics and proteins are firmly adsorbed onto reduced graphene oxide (rGO) nanosheets dispersed in a biopolymer film and then released by individual millisecond-long light pulses generated by a near infrared (NIR) laser. Here graphene plays the dual role of a versatile substrate for temporary storage of drugs and an effective transducer of NIR-light into heat. Drug release appears to be narrowly confined within the size of the laser spot under noninvasive conditions and can be precisely dosed depending on the number of pulses. The approach proposed paves the way for tailor-made pharmacological treatments of chronic diseases, including cancer, anaemia and diabetes.Graphene has recently emerged as a novel material in the biomedical field owing to its optical properties, biocompatibility, large specific surface area and low cost. In this paper, we provide the first demonstration of the possibility of using light to remotely trigger the release of drugs from graphene in a highly controlled manner. Different drugs including chemotherapeutics and proteins are firmly adsorbed onto reduced graphene oxide (rGO) nanosheets dispersed in a biopolymer film and then released by individual millisecond-long light pulses generated by a near infrared (NIR) laser. Here graphene plays the dual role of a versatile substrate for temporary storage of drugs and an effective transducer of NIR-light into heat. Drug release appears to be narrowly confined within the size of the laser spot under noninvasive conditions and can be precisely dosed depending on the number of pulses. The approach proposed paves the way for tailor

  5. Understanding and managing the impact of HPMC variability on drug release from controlled release formulations.

    PubMed

    Zhou, Deliang; Law, Devalina; Reynolds, Judie; Davis, Lynn; Smith, Clifford; Torres, Jose L; Dave, Viraj; Gopinathan, Nishanth; Hernandez, Daniel T; Springman, Mary Kay; Zhou, Casey Chun

    2014-06-01

    The purpose of this study is to identify critical physicochemical properties of hydroxypxropyl methylcellulose (HPMC) that impact the dissolution of a controlled release tablet and develop a strategy to mitigate the HPMC lot-to-lot and vendor-to-vendor variability. A screening experiment was performed to evaluate the impacts of methoxy/hydroxypropyl substitutions, and viscosity on drug release. The chemical diversity of HPMC was explored by nuclear magnetic resonance (NMR), and the erosion rate of HPMC was investigated using various dissolution apparatuses. Statistical evaluation suggested that the hydroxypropyl content was the primary factor impacting the drug release. However, the statistical model prediction was not robust. NMR experiments suggested the existence of structural diversity of HPMC between lots and more significantly between vendors. Review of drug release from hydrophilic matrices indicated that erosion is a key aspect for both poorly soluble and soluble drugs. An erosion rate method was then developed, which enabled the establishment of a robust model and a meaningful HPMC specification. The study revealed that the overall substitution level is not the unique parameter that dictates its release-controlling properties. Fundamental principles of polymer chemistry and dissolution mechanisms are important in the development and manufacturing of hydrophilic matrices with consistent dissolution performance. PMID:24652662

  6. A novel floating controlled release drug delivery system prepared by hot-melt extrusion.

    PubMed

    Vo, Anh Q; Feng, Xin; Morott, Joseph T; Pimparade, Manjeet B; Tiwari, Roshan V; Zhang, Feng; Repka, Michael A

    2016-01-01

    Floating dosage forms are an important formulation strategy for drugs with a narrow absorption window and low intestinal solubility, and for localized gastric treatment. Novel floating pellets were prepared using the hot-melt extrusion (HME) technology. Uniformly foamed strands were created by liquid injection pumping and screw configuration modification. The ammonio methacrylate copolymer (Eudragit® RSPO) foaming structure was formed by a liquid-vapor phase transition inside the strand upon die exiting resulting from the sudden decrease in external pressure, vaporizing the liquid ethanol and vacating the extruded material. This generated uniform vacuous regions in the extrudate. The pellets' internal structure was investigated using scanning electron microscopy (SEM). The formulation constituents' and processing parameters' effects on the drug release profiles, floating force, and the pellets' micromeritic properties were evaluated by design of experiments: all formulations showed zero lag time and excellent floating strength, indicating immediate-floating pellet formation. The pellets' drug release profiles were controlled by multiple independent variables at different time points (⩽ 24 h). Drug loading significantly affected drug release within the first hour, the hydroxypropyl methylcellulose (HPMC) content thereafter. Understanding the variables' effects on the formulations allows for the tailoring of this delivery system to obtain various drug release profiles. PMID:26643801

  7. A repertoire of peptide tags for controlled drug release from injectable noncovalent hydrogel.

    PubMed

    Wieduwild, Robert; Lin, Weilin; Boden, Annett; Kretschmer, Karsten; Zhang, Yixin

    2014-06-01

    A repertoire of conjugable tags for controlling the release of drugs from biomaterials is highly interesting for the development of combinatorial drug administration techniques. This paper describes such a system of 11 peptide tags derived from our previous work on a physical hydrogel system cross-linked through peptide-heparin interactions. The release kinetics of the tags correlate well with their affinity to heparin and obey Fick's second law of diffusion, with the exception of the ATIII peptide, which displays a stable release profile close to a zero-order reaction. A system for release experiments over seven months was built, using the hydrogel matrix as a barrier between the reservoirs of tagged compounds and supernatant. The gel matrix can be injected without affecting the releasing properties. A tagged cyclosporin A derivative was also tested, and its release was monitored by measuring its biological activity. This work represents a design of biomaterials with an integral system of drug delivery, where both the assembly process of the matrix and affinity capture/release of tagged compounds are based on the noncovalent interaction of heparin with one class of peptides. PMID:24825401

  8. Electrically controlled drug release from nanostructured polypyrrole coated on titanium

    NASA Astrophysics Data System (ADS)

    Sirivisoot, Sirinrath; Pareta, Rajesh; Webster, Thomas J.

    2011-02-01

    Previous studies have demonstrated that multi-walled carbon nanotubes grown out of anodized nanotubular titanium (MWNT-Ti) can be used as a sensing electrode for various biomedical applications; such sensors detected the redox reactions of certain molecules, specifically proteins deposited by osteoblasts during extracellular matrix bone formation. Since it is known that polypyrrole (PPy) can release drugs upon electrical stimulation, in this study antibiotics (penicillin/streptomycin, P/S) or an anti-inflammatory drug (dexamethasone, Dex), termed PPy[P/S] or PPy[Dex], respectively, were electrodeposited in PPy on titanium. The objective of the present study was to determine if such drugs can be released from PPy on demand and (by applying a voltage) control cellular behavior important for orthopedic applications. Results showed that PPy films possessed nanometer-scale roughness as analyzed by atomic force microscopy. X-ray photoelectron spectroscopy confirmed the presence of P/S and Dex encapsulated within the PPy films. Results from cyclic voltammetry showed that 80% of the drugs were released on demand when sweep voltages were applied for five cycles at a scan rate of 0.1 V s - 1. Furthermore, osteoblast (bone-forming cells) and fibroblast (fibrous tissue-forming cells) adhesion were determined on the PPy films. Results showed that PPy[Dex] enhanced osteoblast adhesion after 4 h of culture compared to plain Ti. PPy-Ti (with or without anionic drug doping) inhibited fibroblast adhesion compared to plain Ti. These in vitro results confirmed that electrodeposited PPy[P/S] and PPy[Dex] can release drugs on demand to potentially fight bacterial infection, reduce inflammation, promote bone growth or reduce fibroblast functions, further implicating the use of such materials as implant sensors.

  9. Against Their Wills: Children Born Affected by Drugs.

    ERIC Educational Resources Information Center

    Hodgkinson, Harold L.; Outtz, Janice Hamilton

    There is no national policy on assisting drug-using pregnant mothers nor on the children they produce. This paper looks at the issue of "crack-cocaine" and mothers who give birth to children after using drugs during pregnancy. It attempts to lay out what is known, and it puts forth "best guesses" regarding helping children born affected by drugs.…

  10. Computational Modeling of Tumor Response to Drug Release from Vasculature-Bound Nanoparticles

    PubMed Central

    Lowengrub, John; Decuzzi, Paolo; Frieboes, Hermann B.

    2015-01-01

    Systemically injected nanoparticle (NPs) targeting tumor vasculature offer a venue for anti-angiogenic therapies as well as cancer detection and imaging. Clinical application has been limited, however, due to the challenge of elucidating the complex interplay of nanotechnology, drug, and tumor parameters. A critical factor representing the likelihood of endothelial adhesion is the NP vascular affinity, a function of vascular receptor expression and NP size and surface-bound ligand density. We propose a theoretical framework to simulate the tumor response to vasculature-bound drug-loaded NPs and examine the interplay between NP distribution and accumulation as a function of NP vascular affinity, size, and drug loading and release characteristics. The results show that uniform spatial distribution coupled with high vascular affinity is achievable for smaller NPs but not for larger sizes. Consequently, small (100 nm) NPs with high vascular affinity are predicted to be more effective than larger (1000 nm) NPs with similar affinity, even though small NPs have lower drug loading and local drug release compared to the larger NPs. Medium vascular affinity coupled with medium or larger sized NPs is also effective due to a more uniform distribution with higher drug loading and release. Low vascular affinity hampered treatment efficacy regardless of NP size, with larger NPs additionally impeded by heterogeneous distribution and drug release. The results further show that increased drug diffusivity mainly benefits heterogeneously distributed NPs, and would negatively affect efficacy otherwise due to increased wash-out. This model system enables evaluation of efficacy for vascular-targeted drug-loaded NPs as a function of critical NP, drug, and tumor parameters. PMID:26660469

  11. Functional polymer - clay nanotube biocomposites with sustained drug release

    NASA Astrophysics Data System (ADS)

    Lvov, Y.; Tully, J.

    2014-08-01

    By adding 5% (w/w) of halloysite nanotubes that have been modified (loaded) with proteins or drugs it is possible to produce strong and functional biocomposites. Materials loaded with both types of materials were investigated using ultraviolet-visible spectrophotometry and thermogravimetric analysis to determine their release kinetics and overall loading efficiency. It was found that both released over a period of 5-20 hours with two distinct phases being present. An initial "burst stage" of release followed by a period of sustained release. Specifically, for proteins it has been shown that a significant amount (50-75%) remain immobilized even after being dispersed. The typical loading efficiency for both classes of molecules was 10-15%. These modified nanotubes can both strengthen a material and give it unique functionality and possible uses include more effective externally applied antibiotics and immobilized proteins with enhanced stability and reusability.

  12. Phytantriol based liquid crystal provide sustained release of anticancer drug as a novel embolic agent.

    PubMed

    Qin, Lingzhen; Mei, Liling; Shan, Ziyun; Huang, Ying; Pan, Xin; Li, Ge; Gu, Yukun; Wu, Chuanbin

    2016-01-01

    Phytantriol has received increasing amount of attention in drug delivery system, however, the ability of the phytantriol based liquid crystal as a novel embolic agent to provide a sustained release delivery system is yet to be comprehensively demonstrated. The purpose of this study was to prepare a phytantriol-based cubic phase precursor solution loaded with anticancer drug hydroxycamptothecine (HCPT) and evaluate its embolization properties, in vitro drug release and cytotoxicity. Phase behavior of the phytantriol-solvent-water system was investigated by visual inspection and polarized light microscopy, and no phase transition was observed in the presence of HCPT within the studied dose range. Water uptake by the phytantriol matrices was determined gravimetrically, suggesting that the swelling complied with the second order kinetics. In vitro evaluation of embolic efficacy indicated that the isotropic solution displayed a satisfactory embolization effect. In vitro drug release results showed a sustained-release up to 30 days and the release behavior was affected by the initial composition and drug loading. Moreover, the in vitro cytotoxicity and anticancer activity were evaluated by MTT assay. No appreciable mortality was observed for NIH 3T3 cells after 48 h exposure to blank formulations, and the anticancer activity of HCPT-loaded formulations to HepG2 and SMMC7721 cells was strongly dependent on the drug loading and treatment time. Taken together, these results indicate that phytantriol-based cubic phase embolic gelling solution is a promising potential carrier for HCPT delivery to achieve a sustained drug release by vascular embolization, and this technology may be potential for clinical applications. PMID:26035332

  13. Drug Release from Calcium Sulfate-Based Composites

    PubMed Central

    Orellana, Bryan R.; Hilt, J. Zach; Puleo, David A.

    2015-01-01

    To help reduce the need for autografts, calcium sulfate-based bone graft substitutes are being developed to provide a stable platform to aid augmentation while having the ability to release a broad range of bioactive agents. Calcium sulfate (CS) has an excellent reputation as a biocompatible and osteoconductive substance, but addition of bioactive agents may further enhance these properties. Samples were produced with either directly loaded small, hydrophobic molecule (i.e., simvastatin), directly loaded hydrophilic protein (i.e., lysozyme), or 1 and 10 wt% of H6 poly(β-amino ester) (PBAE) particles containing protein. Whereas sustained release of directly loaded simvastatin was achieved, direct loading of small amounts of lysozyme resulted in highly variable release. Direct loading of a larger amount of protein generated a large burst, 65% of total loading, followed by sustained release of protein. Release of lysozyme from 1 wt% PBAE particles embedded into CS was more controllable than when directly loaded, and for 10 wt% of protein-loaded PBAE particles, a higher burst was followed by sustained release, comparable to the results for the high direct loading. Compression testing determined that incorporation of directly loaded drug or drug-loaded PBAE particles weakened CS. In particular, PBAE particles had a significant effect on the strength of the composites, with a 25% and 80% decrease in strength for 1 wt% and 10 wt% particle loadings, respectively. CS-based composites demonstrated the ability to sustainably release both macromolecules and small molecules, supporting the potential for these materials to release a range of therapeutic agents. PMID:24788686

  14. Designer nanoparticles: Incorporating size, shape, and triggered release into nanoscale drug carriers

    PubMed Central

    Caldorera-Moore, Mary; Guimard, Nathalie; Shi, Li; Roy, Krishnendu

    2009-01-01

    Importance of the field Although significant progress has been made in delivering therapeutic agents through micro and nanocarriers, precise control over in vivo biodistribution and disease-responsive drug release has been difficult to achieve. This is critical for the success of next generation drug delivery devices, since newer drugs, designed to interfere with cellular functions, must be efficiently and specifically delivered to diseased cells. The major constraint in achieving this has been our limited repertoire of particle synthesis methods, especially at the nanoscale. Recent developments in generating shape-specific nanocarriers and the potential to combine stimuli-responsive release with nanoscale delivery devices show great promise in overcoming these limitations. Areas covered in this review Here we discuss how recent advancements in fabrication technology allow synthesis of highly monodisperse, stimuli-responsive, drug-carrying nanoparticles of precise geometries. We also review how particle properties, specifically shape and stimuli responsiveness, affect biodistribution, cellular uptake, and drug release. What the reader will gain The reader is introduced to recent developments in intelligent drug nanocarriers and new nanofabrication approaches that can be combined with disease-responsive biomaterials. This will provide insight into the importance of controlling particle geometry and incorporating stimuli responsive materials into drug delivery. PMID:20331355

  15. Polydiacetylene vesicles as a novel drug sustained-release system.

    PubMed

    Guo, Caixin; Liu, Shaoqin; Dai, Zhifei; Jiang, Chang; Li, Wenyuan

    2010-03-01

    Aiming at the enhancement of the physicochemical stability as well as the sustained-release property of conventional liposomes, a novel polymerized vesicular carrier, 10,12-pentacosadiynoic acid (PCDA) vesicles, loaded with paclitaxel as a model hydrophobic drug has been successfully constituted by incorporation of a polymerizable diacetylene into the lipid bilayer vesicles. The polymerized vesicles have been characterized in terms of particle size distribution and zeta-potential. Altering their lipid composition causes the zeta-potential to change from -3+/-1mV to more than -25mV, with a concomitant change in particle size distribution from 29+/-4nm to 149+/-18nm. Dynamic light scattering (DLS) showed that the stability of polymerized vesicles against Triton X-100 was improved greatly compared with the conventional liposomes. In vitro drug release studies show that PCDA-incorporating vesicles reduce the paclitaxel release over the conventional phospholipids vesicles. 69+/-6% paclitaxel is released within 24h from the conventional vesicles, but the insertion of 50% and 75% molar ratio of PCDA changes the amount to 57+/-1% and 32+/-4%, respectively. Our results demonstrate that such novel polymerized vesicles have very good prospect as an anticancer drug carrier. PMID:19896808

  16. [Relation between drug release and the drug status within curcumin-loaded microsphere].

    PubMed

    Chen, De; Liu, Yi; Fan, Kai-yan; Xie, Yi-qiao; Yu, An-an; Xia, Zi-hua; Yang, Fan

    2016-01-01

    To study the relation between drug release and the drug status within curcumin-loaded microsphere, SPG (shirasu porous glass) membrane emulsification was used to prepare the curcumin-PLGA (polylactic-co-glycolic acid) microspheres with three levels of drug loading respectively, and the in vitro release was studied with high-performance liquid chromatography (HPLC). The morphology of microspheres was observed with scanning electron microscopy (SEM), and the drug status was studied with X-ray diffraction (XRD), differential scanning calorimetry (DSC) and infrared analysis (IR). The drug loading of microspheres was (5.85 ± 0.21)%, (11.71 ± 0.39)%, (15.41 ± 0.40)%, respectively. No chemical connection was found between curcumin and PLGA. According to the results of XRD, curcumin dispersed in PLGA as amorphous form within the microspheres of the lowest drug loading, while (2.12 ± 0.64)% and (5.66 ± 0.07)% curcumin crystals was detected in the other two kinds of microspheres, respectively, indicating that the drug status was different within three kinds of microspheres. In the data analysis, we found that PLGA had a limited capacity of dissolving curcumin. When the drug loading exceeded the limit, the excess curcumin would exist in the form of crystals in microspheres independently. Meanwhile, this factor contributes to the difference in drug release behavior of the three groups of microspheres. PMID:27405176

  17. A concise review on smart polymers for controlled drug release.

    PubMed

    Aghabegi Moghanjoughi, Arezou; Khoshnevis, Dorna; Zarrabi, Ali

    2016-06-01

    Design and synthesis of efficient drug delivery systems are of critical importance in health care management. Innovations in materials chemistry especially in polymer field allows introduction of advanced drug delivery systems since polymers could provide controlled release of drugs in predetermined doses over long periods, cyclic and tunable dosages. To this end, researchers have taken advantages of smart polymers since they can undergo large reversible, chemical, or physical fluctuations as responses to small changes in environmental conditions, for instance, in pH, temperature, light, and phase transition. The present review aims to highlight various kinds of smart polymers, which are used in controlled drug delivery systems as well as mechanisms of action and their applications. PMID:26744179

  18. Application of experimental design methodology in development and optimization of drug release method.

    PubMed

    Kincl, M; Turk, S; Vrecer, F

    2005-03-01

    The aim of our research was to apply experimental design methodology in the development and optimization of drug release methods. Diclofenac sodium (2-[(2,6-dichlorophenyl)amino]benzeneacetic acid monosodium salt) was selected as a model drug and Naklofen retard prolonged release tablets, containing 100 mg of diclofenac sodium, were chosen as a model prolonged release system. On the basis of previous results, a three-level three-factorial Box-Behnken experimental design was used to characterize and optimize three physicochemical parameters, i.e. rotation speeds of the stirring elements, pH, and ionic strengths of the dissolution medium, affecting the release of diclofenac sodium from the tablets. The chosen dependent variables (responses) were a cumulative percentage of dissolved diclofenac sodium in 2, 6, 12 and 24 h. For estimation of coefficients in the approximating polynomial function, the least square regression method was applied. Afterwards, the information about the model reliability was verified by using the analysis of variance (ANOVA). The estimation of model factors' significance was performed by Student's t-test. For investigation of the shape of the predicted response surfaces and for model optimization, the canonical analysis was applied. Our study proved that experimental design methodology could efficiently be applied for characterization and optimization of analytical parameters affecting drug release and that it is an economical way of obtaining the maximum amount of information in a short period of time and with the fewest number of experiments. PMID:15707730

  19. Encapsulation and release of a hydrophobic drug from hydroxyapatite coated liposomes.

    PubMed

    Xu, Qingguo; Tanaka, Yasuhiro; Czernuszka, Jan T

    2007-06-01

    Hydroxyapatite (HA) coated liposomes (HACL) have been successfully manufactured and filled with a model hydrophobic (lipophilic) drug, indomethacin (IMC). These HACL particles have been characterized in terms of particle size and zeta-potential. The liposomes are formed from 1,2-dimyristoyl-sn-glycero-3-phosphate (DMPA) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). Altering their relative proportions caused the zeta-potential to change from -38.8 to -67.0 mV, with a concomitant change in phase transition temperature from 36.4 to 53.3 degrees C. These changes also affect the drug loading efficiency. The release profiles of IMC have been measured. HA coating of the liposome reduces the release rate of IMC over uncoated liposomes. Under the present experimental conditions 70% of the drug is released after approximately 5h from the liposome, but coating with HA changes this time to over 20 h. Perhaps most importantly, it has been observed that for uncoated liposomes, IMC is released at a greater rate at pH=7.4 than at pH=4. However, coating with HA reduced the rate at pH=7.4 compared to pH=4. This behaviour arises because IMC is more soluble under basic conditions, but HA is more soluble under acidic conditions. This behaviour shows that it is now possible to have environmental control over the release of drugs from HA-coated liposomes. PMID:17331574

  20. Electrically credible polymer gel for controlled release of drugs

    NASA Astrophysics Data System (ADS)

    Kwon, Ick Chan; Bae, You Han; Kim, Sung Wan

    1991-11-01

    NEW controlled drug-delivery systems are being explored to overcome the disadvantages of conventional dosage forms1. For example, stimulated drug-delivery has been used to overcome the tolerance problems that occur with a constant delivery rate, to mimic the physiological pattern of hormonal concentration and to supply drugs on demand1,2. Stimuli-sensitive polymers, which are potentially useful for pulsed drug delivery, experience changes in either their structure or their chemical properties in response to changes in environmental conditions2. Environmental stimuli include temperature3,4, pH5,6, light (ultraviolet7 or visible8), electric field9-12 or certain chemicals13. Volume changes of stimuli-sensitive gel networks are particularly responsive to external stimuli, but swelling is slow to occur14,15. As well as being useful in the controlled release of drugs, such systems also provide insight into intermolecular interactions16. Here we report on a novel polymeric system, which rapidly changes from a solid state to solution in response to small electric currents, by disintegration of the solid polymer complex into two water-soluble polymers. We show that the modulated release of insulin, and by extension other macromolecules, can be achieved with this polymeric system.

  1. Effect of degree of esterification of pectin and calcium amount on drug release from pectin-based matrix tablets.

    PubMed

    Sungthongjeen, Srisagul; Sriamornsak, Pornsak; Pitaksuteepong, Tasana; Somsiri, Atawit; Puttipipatkhachorn, Satit

    2004-02-12

    The aim of this work was to assess the effect of 2 formulation variables, the pectin type (with different degrees of esterification [DEs]) and the amount of calcium, on drug release from pectin-based matrix tablets. Pectin matrix tablets were prepared by blending indomethacin (a model drug), pectin powder, and various amounts of calcium acetate and then tableting by automatic hydraulic press machine. Differential scanning calorimetry, powder x-ray diffraction, and Fourier transformed-infrared spectroscopy studies of the compressed tablets revealed no drug-polymer interaction and the existence of drug with low crystallinity. The in-vitro release studies in phosphate buffer (United States Pharmacopeia) and tris buffer indicated that the lower the DE, the greater the time for 50% of drug release (T50). This finding is probably because of the increased binding capacity of pectin to calcium. However, when the calcium was excluded, the pectins with different DEs showed similar release pattern with insignificant difference of T50. When the amount of calcium acetate was increased from 0 to 12 mg/tablet, the drug release was significantly slower. However, a large amount of added calcium (ie, 24 mg/tablet) produced greater drug release because of the partial disintegration of tablets. The results were more pronounced in phosphate buffer, where the phosphate ions induced the precipitation of calcium phosphate. In conclusion, both pectin type and added calcium affect the drug release from the pectin-based matrix tablets. PMID:15198530

  2. Encapsulation of methotrexate loaded magnetic microcapsules for magnetic drug targeting and controlled drug release

    NASA Astrophysics Data System (ADS)

    Chakkarapani, Prabu; Subbiah, Latha; Palanisamy, Selvamani; Bibiana, Arputha; Ahrentorp, Fredrik; Jonasson, Christian; Johansson, Christer

    2015-04-01

    We report on the development and evaluation of methotrexate magnetic microcapsules (MMC) for targeted rheumatoid arthritis therapy. Methotrexate was loaded into CaCO3-PSS (poly (sodium 4-styrenesulfonate)) doped microparticles that were coated successively with poly (allylamine hydrochloride) and poly (sodium 4-styrenesulfonate) by layer-by-layer technique. Ferrofluid was incorporated between the polyelectrolyte layers. CaCO3-PSS core was etched by incubation with EDTA yielding spherical MMC. The MMC were evaluated for various physicochemical, pharmaceutical parameters and magnetic properties. Surface morphology, crystallinity, particle size, zeta potential, encapsulation efficiency, loading capacity, drug release pattern, release kinetics and AC susceptibility studies revealed spherical particles of ~3 μm size were obtained with a net zeta potential of +24.5 mV, 56% encapsulation and 18.6% drug loading capacity, 96% of cumulative drug release obeyed Hixson-Crowell model release kinetics. Drug excipient interaction, surface area, thermal and storage stability studies for the prepared MMC was also evaluated. The developed MMC offer a promising mode of targeted and sustained release drug delivery for rheumatoid arthritis therapy.

  3. Nanoporous anodic titanium dioxide layers as potential drug delivery systems: Drug release kinetics and mechanism.

    PubMed

    Jarosz, Magdalena; Pawlik, Anna; Szuwarzyński, Michał; Jaskuła, Marian; Sulka, Grzegorz D

    2016-07-01

    Nanoporous anodic titanium dioxide (ATO) layers on Ti foil were prepared via a three step anodization process in an electrolyte based on an ethylene glycol solution with fluoride ions. Some of the ATO samples were heat-treated in order to achieve two different crystallographic structures - anatase (400°C) and a mixture of anatase and rutile (600°C). The structural and morphological characterizations of ATO layers were performed using a field emission scanning electron microscope (SEM). The hydrophilicity of ATO layers was determined with contact angle measurements using distilled water. Ibuprofen and gentamicin were loaded effectively inside the ATO nanopores. Afterwards, an in vitro drug release was conducted for 24h under a static and dynamic flow conditions in a phosphate buffer solution at 37°C. The drug concentrations were determined using UV-Vis spectrophotometry. The absorbance of ibuprofen was measured directly at 222nm, whether gentamicin was determined as a complex with silver nanoparticles (Ag NPs) at 394nm. Both compounds exhibited long term release profiles, despite the ATO structure. A new release model, based on the desorption of the drug from the ATO top surface followed by the desorption and diffusion of the drug from the nanopores, was derived. The proposed release model was fitted to the experimental drug release profiles, and kinetic parameters were calculated. PMID:27037782

  4. How Do Beta Blocker Drugs Affect Exercise?

    MedlinePlus

    ... American Heart area Search by State SELECT YOUR LANGUAGE Español (Spanish) 简体中文 (Traditional Chinese) 繁体中文 (Simplified Chinese) ... used because beta blockers affect everyone differently. The second way to monitor your intensity is simpler: making ...

  5. Design, synthesis, characterization and drug release kinetics of PAMAM dendrimer based drug formulations

    NASA Astrophysics Data System (ADS)

    Kurtoglu, Yunus Emre

    The drug release characteristics of G4-polyamidoamine (PAMAM) dendrimer-ibuprofen conjugates with ester, amide, and peptide linkers were investigated, in addition to a linear PEG-ibuprofen conjugate to understand the effect of architecture and linker on drug release. Ibuprofen was directly conjugated to NH2 -terminated dendrimer by an amide bond and OH-terminated dendrimer by an ester bond. A tetra-peptide linked dendrimer conjugate and a linear mPEG-ibuprofen conjugate were also studied for comparison to direct linked dendrimer conjugates. It is demonstrated that the 3-D nanoscale architecture of PAMAM dendrimer-drug conjugates, along with linking chemistry govern the drug release mechanisms as well as kinetics. Understanding these structural effects on their drug release characteristics is crucial for design of dendrimer conjugates with high efficacy such as poly(amidoamine) dendrimer-N-Acetylcysteine conjugates with disulfide linkages. N-Acetylcysteine (NAC) is an anti-inflammatory agent with significant potential for clinical use in the treatment of neuroinflammation, stroke and cerebral palsy. A poly(amidoamine) dendrimer-NAC conjugate that contains a disulfide linkage was synthesized and evaluated for its release kinetics in the presence of glutathione (GSH), Cysteine (Cys), and bovine serum albumin (BSA) at both physiological and lysosomal pH. FITC-labeled conjugates showed that they enter cells rapidly and localize in the cytoplasm of lipopolysaccharide (LPS)-activated microglial cells. The efficacy of the dendrimer-NAC conjugate was measured in activated microglial cells using reactive oxygen species (ROS) assays. The conjugates showed an order of magnitude increase in anti-oxidant activity compared to free drug. When combined with intrinsic and ligand-based targeting with dendrimers, these types of GSH sensitive nanodevices can lead to improved drug release profiles and in vivo efficacy.

  6. Equipment for drug release testing of medicated chewing gums.

    PubMed

    Kvist, L C; Andersson, S B; Berglund, J; Wennergren, B; Fors, S M

    2000-04-01

    An apparatus was specially designed and constructed for release testing of medicated chewing gums. The adjustable instrumental settings such as temperature, chewing frequency, chewing time, volume of test medium, distance between the jaws and twisting angle increased the versatility of the apparatus. Selection of the test medium was also an important parameter. Each sample was kneaded mechanically in separate test chambers and the drug release was followed by sampling and HPLC analysis. Different gum formulations were tested and the obtained results demonstrated satisfactory release curves for a variety of formulations and active ingredients. The tested gum formulations comprised nicotine, meclizine, dimenhydrinate and xylitol. The apparatus proved to be suitable in product control of commercial batches but also a useful tool in the research and development of medicated gum formulations. PMID:10766358

  7. Zinc cross-linked hydroxamated alginates for pulsed drug release

    PubMed Central

    Raut, Neha S; Deshmukh, Prasad R; Umekar, Milind J; Kotagale, Nandkishor R

    2013-01-01

    Introduction: Alginates can be tailored chemically to improve solubility, physicochemical, and biological properties and its complexation with metal ion is useful for controlling the drug release. Materials And Methods: Synthesized N,O-dimethyl, N-methyl, or N-Benzyl hydroxylamine derivatives of sodium alginate were subsequently complexed with zinc to form beads. Hydroxamation of sodium alginate was confirmed by Fourier transform infra-red spectroscopy (FTIR) and differential scanning calorimetry (DSC). Results: The synthesized polymeric material exhibited reduced aqueous, HCl and NaOH solubility. The hydroxamated derivatives demonstrated pulsed release where change in pH of the dissolution medium stimulated the atenolol release. Conclusion: Atenolol loaded Zn cross-linked polymeric beads demonstrated the sustained the plasma drug levels with increased half-life. Although the synthesized derivatives greatly altered the aqueous solubility of sodium alginate, no significant differences in in vitro and in vivo atenolol release behavior amongst the N,O-dimethyl, N-methyl, or N-Benzyl hydroxylamine derivatives of sodium alginate were observed. PMID:24350039

  8. pH-controlled drug release for dental applications

    NASA Astrophysics Data System (ADS)

    Wironen, John Francis

    A large proportion of the dental fillings replaced at present are revised because of the perceived presence of a recurrent caries under or adjacent to the restoration. Many of these perceived caries may not exist, while others may go undetected. This work describes the preparation of drug loaded polymer microspheres that sense the presence of the bacteria that cause caries by the associated presence of acid by-products of digestion. These microspheres are designed to swell and release their antimicrobial drugs once the pH drops to a level that would normally cause caries. The preparation of the microspheres as well as their loading with potassium fluoride, chlorhexidine digluconate, chlorhexidine dihydrochloride, chlorhexidine diacetate, and tetracycline hydrochloride are described. A detailed study of the controlled release behavior of fluoride as a function of polymer composition and pH is presented first. A study of the release kinetics of potassium fluoride, chlorhexidine digluconate, diacetate, dihydrochloride, and tetracycline hydrochloride as a function of pH in the same polymer system is then presented. Additional studies of the swelling kinetics of chlorhexidine-loaded microspheres in various pH buffers are discussed with special reference to correlations with the controlled-release data. Finally, an experiment in which the microspheres are tested in an in vitro bacteria model that includes Streptococcus mutans is presented and discussed in detail.

  9. Tailored Sequential Drug Release from Bilayered Calcium Sulfate Composites

    PubMed Central

    Orellana, Bryan R.; Puleo, David A.

    2014-01-01

    The current standard for treating infected bony defects, such as those caused by periodontal disease, requires multiple time-consuming steps and often multiple procedures to fight the infection and recover lost tissue. Releasing an antibiotic followed by an osteogenic agent from a synthetic bone graft substitute could allow for a streamlined treatment, reducing the need for multiple surgeries and thereby shortening recovery time. Tailorable bilayered calcium sulfate (CS) bone graft substitutes were developed with the ability to sequentially release multiple therapeutic agents. Bilayered composite samples having a shell and core geometry were fabricated with varying amounts (1 or 10 wt%) of metronidazole-loaded poly poly(lactic-co-glycolic acid) (PLGA) particles embedded in the shell and simvastatin directly loaded into either the shell, core, or both. Microcomputed tomography (MicroCT) images showed the overall layered geometry as well as homogenous distribution of PLGA within the shells. Dissolution studies demonstrated that the amount of PLGA particles (i.e., 1 vs. 10 wt%) had a small but significant effect on the erosion rate (3% vs. 3.4% per day). Mechanical testing determined that introducing a layered geometry had a significant effect on the compressive strength, with an average reduction of 35%, but properties were comparable to mandibular trabecular bone. Sustained release of simvastatin directly loaded into CS demonstrated that changing the shell to core volume ratio dictates the duration of drug release from each layer. When loaded together in the shell or in separate layers, sequential release of metronidazole and simvastatin was achieved. By introducing a tunable layered geometry capable of releasing multiple drugs, CS-based bone graft substitutes could be tailored in order to help streamline multiple steps needed to regenerate tissue in infected defects. PMID:25175211

  10. One-step fabrication of inorganic/organic hybrid microspheres with tunable surface texture for controlled drug release application.

    PubMed

    Dong, Hua; Tang, Guannan; Ma, Ting; Cao, Xiaodong

    2016-01-01

    In this paper, we report one-step fabrication of poly(lactide-co-glycolic acid)/titanium oxide (PLGA/TiO2) hybrid microspheres with tunable surface texture via droplet-based microfluidics. Surface texture of microspheres can be continuously tuned by changing the mass ratio between titanium tetraisopropoxide (TTIP) and PLGA in the dispersed phase. The fast hydrolysis of TTIP on the droplet surface can generate a thin shell membrane, resulting in a wrinkled surface after extraction of organic solvent. In vitro drug release monitoring of tanshinone IIA-loaded PLGA/TiO2 hybrid microsphere reveals that surface texture can affect the drug release rate to a large extent without sacrificing the drug encapsulation efficiency. Our finding might benefit the sustained drug delivery where variable drug release rate and high drug encapsulation efficiency are both required. PMID:26610930

  11. Utilizing the protein corona around silica nanoparticles for dual drug loading and release

    NASA Astrophysics Data System (ADS)

    Shahabi, Shakiba; Treccani, Laura; Dringen, Ralf; Rezwan, Kurosch

    2015-10-01

    A protein corona forms spontaneously around silica nanoparticles (SNPs) in serum-containing media. To test whether this protein corona can be utilized for the loading and release of anticancer drugs we incorporated the hydrophilic doxorubicin, the hydrophobic meloxicam as well as their combination in the corona around SNPs. The application of corona-covered SNPs to osteosarcoma cells revealed that drug-free particles did not affect the cell viability. In contrast, SNPs carrying a protein corona with doxorubicin or meloxicam lowered the cell proliferation in a concentration-dependent manner. In addition, these particles had an even greater antiproliferative potential than the respective concentrations of free drugs. The best antiproliferative effects were observed for SNPs containing both doxorubicin and meloxicam in their corona. Co-localization studies revealed the presence of doxorubicin fluorescence in the nucleus and lysosomes of cells exposed to doxorubicin-containing coated SNPs, suggesting that endocytotic uptake of the SNPs facilitates the cellular accumulation of the drug. Our data demonstrate that the protein corona, which spontaneously forms around nanoparticles, can be efficiently exploited for loading the particles with multiple drugs for therapeutic purposes. As drugs are efficiently released from such particles they may have a great potential for nanomedical applications.A protein corona forms spontaneously around silica nanoparticles (SNPs) in serum-containing media. To test whether this protein corona can be utilized for the loading and release of anticancer drugs we incorporated the hydrophilic doxorubicin, the hydrophobic meloxicam as well as their combination in the corona around SNPs. The application of corona-covered SNPs to osteosarcoma cells revealed that drug-free particles did not affect the cell viability. In contrast, SNPs carrying a protein corona with doxorubicin or meloxicam lowered the cell proliferation in a concentration

  12. Channeling agent and drug release from a central core matrix tablet.

    PubMed

    González-Rodríguez, M L; Pérez-Martínez, J I; Merino, S; Fini, A; Rabasco, A M

    2001-05-01

    A new oral dosage form for controlled and complete release of drug after a predetermined lag time is described. The system, designed to exploit the relatively constant small intestine transit time, consists of a drug-containing core coated with a polymeric matrix formed by a channeling agent (NaCl, mannitol, and Emdex) and an inert polymer (Eudragit RS100). The lag time was found to be dependent on type and particle size of the channeling substances used. Also, rheological properties of the binary mixtures (channeling substance--polymer) can affect the lag time periods. On the other hand, the release kinetics were found to be influenced significantly by excipient type and particle size. Results obtained from in vitro dissolution testing demonstrated that this device potentially could be used to deliver drugs orally for up to once-a-day dosing at controllable rates. PMID:11448051

  13. Factors Affecting the Timing of Signal Detection of Adverse Drug Reactions.

    PubMed

    Hashiguchi, Masayuki; Imai, Shungo; Uehara, Keiko; Maruyama, Junya; Shimizu, Mikiko; Mochizuki, Mayumi

    2015-01-01

    We investigated factors affecting the timing of signal detection by comparing variations in reporting time of known and unknown ADRs after initial drug release in the USA. Data on adverse event reactions (AERs) submitted to U.S. FDA was used. Six ADRs associated with 6 drugs (rosuvastatin, aripiprazole, teriparatide, telithromycin, exenatide, varenicline) were investigated: Changes in the proportional reporting ratio, reporting odds ratio, and information component as indexes of signal detection were followed every 3 months after each drugs release, and the time for detection of signals was investigated. The time for the detection of signal to be detected after drug release in the USA was 2-10 months for known ADRs and 19-44 months for unknown ones. The median lag time for known and unknown ADRs was 99.0-122.5 days and 185.5-306.0 days, respectively. When the FDA released advisory information on rare but potentially serious health risks of an unknown ADR, the time lag to report from the onset of ADRs to the FDA was shorter. This study suggested that one factor affecting signal detection time is whether an ADR was known or unknown at release. PMID:26641634

  14. Photonic monitoring of chitosan nanostructured alginate microcapsules for drug release

    NASA Astrophysics Data System (ADS)

    Khajuria, Deepak Kumar; Konnur, Manish C.; Vasireddi, Ramakrishna; Roy Mahapatra, D.

    2015-02-01

    By using a novel microfluidic set-up for drug screening applications, this study examines delivery of a novel risedronate based drug formulation for treatment of osteoporosis that was developed to overcome the usual shortcomings of risedronate, such as its low bioavailability and adverse gastric effects. Risedronate nanoparticles were prepared using muco-adhesive polymers such as chitosan as matrix for improving the intestinal cellular absorption of risedronate and also using a gastric-resistant polymer such as sodium alginate for reducing the gastric inflammation of risedronate. The in-vitro characteristics of the alginate encapsulated chitosan nanoparticles are investigated, including their stability, muco-adhesiveness, and Caco-2 cell permeability. Fluorescent markers are tagged with the polymers and their morphology within the microcapsules is imaged at various stages of drug release.

  15. Water boiling inside carbon nanotubes: toward efficient drug release.

    PubMed

    Chaban, Vitaly V; Prezhdo, Oleg V

    2011-07-26

    We show using molecular dynamics simulation that spatial confinement of water inside carbon nanotubes (CNTs) substantially increases its boiling temperature and that a small temperature growth above the boiling point dramatically raises the inside pressure. Capillary theory successfully predicts the boiling point elevation down to 2 nm, below which large deviations between the theory and atomistic simulation take place. Water behaves qualitatively different inside narrow CNTs, exhibiting transition into an unusual phase, where pressure is gas-like and grows linearly with temperature, while the diffusion constant is temperature-independent. Precise control over boiling by CNT diameter, together with the rapid growth of inside pressure above the boiling point, suggests a novel drug delivery protocol. Polar drug molecules are packaged inside CNTs; the latter are delivered into living tissues and heated by laser. Solvent boiling facilitates drug release. PMID:21648482

  16. Characterizing the Network of Drugs and Their Affected Metabolic Subpathways

    PubMed Central

    Li, Jing; Han, Junwei; Wang, Shuyuan; Yao, Qianlan; Wang, Yingying; Zhang, Yunpeng; Zhang, Chunlong; Xu, Yanjun; Jiang, Wei; Li, Xia

    2012-01-01

    A fundamental issue in biology and medicine is illustration of the overall drug impact which is always the consequence of changes in local regions of metabolic pathways (subpathways). To gain insights into the global relationship between drugs and their affected metabolic subpathways, we constructed a drug–metabolic subpathway network (DRSN). This network included 3925 significant drug–metabolic subpathway associations representing drug dual effects. Through analyses based on network biology, we found that if drugs were linked to the same subpathways in the DRSN, they tended to share the same indications and side effects. Furthermore, if drugs shared more subpathways, they tended to share more side effects. We then calculated the association score by integrating drug-affected subpathways and disease-related subpathways to quantify the extent of the associations between each drug class and disease class. The results showed some close drug–disease associations such as sex hormone drugs and cancer suggesting drug dual effects. Surprisingly, most drugs displayed close associations with their side effects rather than their indications. To further investigate the mechanism of drug dual effects, we classified all the subpathways in the DRSN into therapeutic and non-therapeutic subpathways representing drug therapeutic effects and side effects. Compared to drug side effects, the therapeutic effects tended to work through tissue-specific genes and these genes tend to be expressed in the adrenal gland, liver and kidney; while drug side effects always occurred in the liver, bone marrow and trachea. Taken together, the DRSN could provide great insights into understanding the global relationship between drugs and metabolic subpathways. PMID:23112813

  17. Magnetically Stimulated Release of a Model Drug From a Magnetic Drug Carrier

    NASA Astrophysics Data System (ADS)

    Riley, Tom; Evans, Ben

    The use of particles in the micro and nanometer ranges has become increasingly important as therapeutic tools in medicine. In particular, magnetically-active particles may allow for magnetically-controlled release of drugs at targeted locations. The drugs can be delivered directly to cancerous tumors at desired concentrations. While hydrogel-based microspheres have been commonly proposed for such purposes, there is also a need for a lipophilic magnetic microsphere for delivery of poorly-soluble pharmaceuticals. We have created a well-dispersed suspension of iron oxide nanoparticles in a silicone matrix, and have used the material to manufacture microspheres in sizes ranging from 100nm to 50 microns. Our spheres are stable in aqueous suspensions, yet their silicone matrix is uniquely suited for the transport and delivery of hydrophobic pharmaceuticals. A high concentration of magnetic nanoparticles (50% wt.) enables magnetic localization, magnetic heating (hyperthermia), and magnetic stimulation to trigger drug release. Using fluorescein as a model drug, we use UV-visible spectroscopy to show a slow native release rate of the hydrophobic fluorescein from the spheres. We use these measurements to quantify the loading capacity of the microspheres, and we show results of magnetically-stimulated drug release using a DM100 field applicator (nanoScale Biomagnetics).

  18. Amphiphilic beads as depots for sustained drug release integrated into fibrillar scaffolds.

    PubMed

    Gaharwar, Akhilesh K; Mihaila, Silvia M; Kulkarni, Ashish A; Patel, Alpesh; Di Luca, Andrea; Reis, Rui L; Gomes, Manuela E; van Blitterswijk, Clemens; Moroni, Lorenzo; Khademhosseini, Ali

    2014-08-10

    Native extracellular matrix (ECM) is a complex fibrous structure loaded with bioactive cues that affects the surrounding cells. A promising strategy to mimicking native tissue architecture for tissue engineering applications is to engineer fibrous scaffolds using electrospinning. By loading appropriate bioactive cues within these fibrous scaffolds, various cellular functions such as cell adhesion, proliferation and differentiation can be regulated. Here, we report on the encapsulation and sustained release of a model hydrophobic drug (dexamethasone (Dex)) within beaded fibrillar scaffold of poly(ethylene oxide terephthalate)-poly(butylene terephthalate) (PEOT/PBT), a polyether-ester multiblock copolymer to direct differentiation of human mesenchymal stem cells (hMSCs). The amphiphilic beads act as depots for sustained drug release that is integrated into the fibrillar scaffolds. The entrapment of Dex within the beaded structure results in sustained release of the drug over the period of 28days. This is mainly attributed to the diffusion driven release of Dex from the amphiphilic electrospun scaffolds. In vitro results indicate that hMSCs cultured on Dex containing beaded fibrillar scaffolds exhibit an increase in osteogenic differentiation potential, as evidenced by increased alkaline phosphatase (ALP) activity, compared to the direct infusion of Dex in the culture medium. The formation of a mineralized matrix is also significantly enhanced due to the controlled Dex release from the fibrous scaffolds. This approach can be used to engineer scaffolds with appropriate chemical cues to direct tissue regeneration. PMID:24794894

  19. Serotonin and acetylcholine affect the release of prolactin and growth hormone from pituitary glands of domestic fowl in vitro in the presence of hypothalamic tissue.

    PubMed

    Hall, T R; Harvey, S; Chadwick, A

    1984-04-01

    Anterior pituitary glands from broiler fowl were incubated alone or with hypothalamic tissue in medium containing either serotonin or serotoninergic drugs, acetylcholine or cholinergic drugs, and the release of prolactin (Prl) and growth hormone (GH) measured by homologous radioimmunoassays. The neurotransmitters and drugs affected the release of hormones from the pituitary gland only when hypothalamic tissue was also present. Serotonin and its agonist quipazine stimulated the release of Prl and inhibited release of GH in a concentration-related manner. The antagonist methysergide blocked the effects of serotonin and quipazine on Prl. Acetylcholine and its agonist pilocarpine also stimulated release of Prl and inhibited release of GH in a concentration-related manner. Atropine blocked these responses. The results show that serotonin and acetylcholine affect pituitary hormone secretion by acting on the hypothalamus. They may stimulate the secretion of a Prl releasing hormone and somatostatin. PMID:6144226

  20. Factors That Affect Adolescent Drug Users' Suicide Attempts

    PubMed Central

    Song, Hokwang

    2016-01-01

    Drug abuse has been widely linked to suicide risk. We examined the factors that affect adolescent drug users' suicide attempts in South Korea. This study analyzed the data of 311 adolescents who had used drugs such as inhalants, psychotropic drugs, and marijuana (195 males and 116 females). Among 311 subjects, 109 (35.0%) had attempted suicide during the last 12 months. After adjusting for other variables, depressive mood (OR=19.79) and poly-drug use (OR=2.79), and low/middle levels of academic achievement compared with a high level (OR=3.72 and 4.38) were independently associated with increased odds of a suicide attempt, while better perceived health (OR=0.32) was independently associated with reduced odds of a suicide attempt. For adolescent drug users, preventive work should be directed toward the active treatment of drug use, depression, and physical health and reinforcing proper coping strategies for academic and other stress. PMID:27247604

  1. Factors That Affect Adolescent Drug Users' Suicide Attempts.

    PubMed

    Park, Subin; Song, Hokwang

    2016-05-01

    Drug abuse has been widely linked to suicide risk. We examined the factors that affect adolescent drug users' suicide attempts in South Korea. This study analyzed the data of 311 adolescents who had used drugs such as inhalants, psychotropic drugs, and marijuana (195 males and 116 females). Among 311 subjects, 109 (35.0%) had attempted suicide during the last 12 months. After adjusting for other variables, depressive mood (OR=19.79) and poly-drug use (OR=2.79), and low/middle levels of academic achievement compared with a high level (OR=3.72 and 4.38) were independently associated with increased odds of a suicide attempt, while better perceived health (OR=0.32) was independently associated with reduced odds of a suicide attempt. For adolescent drug users, preventive work should be directed toward the active treatment of drug use, depression, and physical health and reinforcing proper coping strategies for academic and other stress. PMID:27247604

  2. Sustained Release Intraocular Drug Delivery Devices for Treatment of Uveitis

    PubMed Central

    Haghjou, Nahid; Soheilian, Masoud; Abdekhodaie, Mohammad Jafar

    2011-01-01

    Corticosteroids have been the mainstay of uveitis therapy. When intraocular inflammation is unresponsive to steroids, or steroid related side effects become a concern, steroid-sparing medications may be administered which can be classified into immunosuppressive and immunomodulatory agents. Uveitis treatment can be delivered systemically, topically, periocularly or intraocularly. All of the above mentioned medications can entail significant systemic side effects, particularly if administered for prolonged durations, which may become treatment-limiting. Some medications, particularly hydrophobic compounds, may poorly cross the blood–retinal barrier. Topical medications, which have the least side effects, do not penetrate well into the posterior segment and are unsuitable for posterior uveitis which is often sight-threatening. Intraocular or periocular injections can deliver relatively high doses of drug to the eye with few or no systemic side effects. However, such injections are associated with significant complications and must often be repeated at regular intervals. Compliance with any form of regular medication can be a problem, particularly if its administration is associated with discomfort or if side effects are unpleasant. To overcome the above-mentioned limitations, an increasing number of sustained-release drug delivery devices using different mechanisms and containing a variety of agents have been developed to treat uveitis. This review discusses various current and future sustained-release ophthalmic drug delivery systems for treatment of uveitis. PMID:22454753

  3. Externally Controlled Triggered-Release of Drug from PLGA Micro and Nanoparticles

    PubMed Central

    Hua, Xin; Tan, Shengnan; Bandara, H. M. H. N.; Fu, Yujie; Liu, Siguo; Smyth, Hugh D. C.

    2014-01-01

    Biofilm infections are extremely hard to eradicate and controlled, triggered and controlled drug release properties may prolong drug release time. In this study, the ability to externally control drug release from micro and nanoparticles was investigated. We prepared micro/nanoparticles containing ciprofloxacin (CIP) and magnetic nanoparticles encapsulated in poly (lactic-co-glycolic acid) PLGA. Both micro/nanoparticles were observed to have narrow size distributions. We investigated and compared their passive and externally triggered drug release properties based on their different encapsulation structures for the nano and micro systems. In passive release studies, CIP demonstrated a fast rate of release in first 2 days which then slowed and sustained release for approximately 4 weeks. Significantly, magnetic nanoparticles containing systems all showed ability to have triggered drug release when exposed to an external oscillating magnetic field (OMF). An experiment where the OMF was turned on and off also confirmed the ability to control the drug release in a pulsatile manner. The magnetically triggered release resulted in a 2-fold drug release increase compared with normal passive release. To confirm drug integrity following release, the antibacterial activity of released drug was evaluated in Pseudomonas aeruginosa biofilms in vitro. CIP maintained its antimicrobial activity after encapsulation and triggered release. PMID:25479357

  4. Spray-dried high-amylose sodium carboxymethyl starch: impact of α-amylase on drug-release profile.

    PubMed

    Nabais, Teresa; Zaraa, Sarra; Leclair, Grégoire

    2016-11-01

    Spray-dried high-amylose sodium carboxymethyl starch (SD HASCA) is a promising pharmaceutical excipient for sustained-release (SR) matrix tablets produced by direct compression. The presence of α-amylase in the gastrointestinal tract and the variations of the gastric residence time of non-disintegrating dosage forms may affect the presystemic metabolism of this excipient and, consequently, the drug-release profile from formulations produced with SD HASCA. In this study, the influence of α-amylase and the residence time in acidic conditions on the drug-release profile was evaluated for a once-daily acetaminophen formulation (Acetaminophen SR) and a once-daily tramadol hydrochloride formulation (Tramadol SR). Both formulations were based on SD HASCA. α-Amylase concentrations ranging from 0 IU/L to 20000 IU/L did not significantly affect the drug-release profiles of acetaminophen and tramadol hydrochloride from SD HASCA tablets (f2 > 50) for all but only one of the studied conditions (f2 = 47). Moreover, the drug-release properties from both SD HASCA formulations were not significantly different when the residence time in acidic medium was 1 h or 3 h. An increase in α-amylase concentration led to an increase in the importance of polymer erosion as the main mechanism of drug-release instead of drug diffusion, for both formulations and both residence times, even if release profiles remained comparable. As such, it is expected that α-amylase concentration and residence time in the stomach will not clinically affect the performance of both SD HASCA SR formulations, even if the mechanism of release itself may be affected. PMID:27109692

  5. The effects of irradiation on controlled drug delivery/controlled drug release systems

    NASA Astrophysics Data System (ADS)

    Ražem, Dušan; Katušin-Ražem, Branka

    2008-03-01

    The research of radiation effects on drugs over the past 60 years has mainly dealt with radiation sterilization of individual active pharmaceutical ingredients (APIs) in the form of pure substances or injectable solutions. However, the emergence of novel systems for drug administration and targeting via controlled drug delivery (CDD) and/or controlled drug release (CDR) has extended the use of irradiation with respect to pharmaceuticals: the capacity of radiation to act as an initiator of crosslinking has been used in the manufacturing and modification of a number of polymeric carriers with an added advantage of reducing the microbial load of products at the same time. The application of irradiation to these novel systems requires the understanding of radiation action not only on APIs alone but also on drug carriers and on the functioning of the integral CDD/CDR systems. In this paper, the significance of CDD/CDR systems is considered with a special emphasis on the role of irradiation for sterilization and crosslinking in the developments over the past 15 years. Radiation sterilization, crosslinking and degradation of the principal forms of drug carrier systems and the effects of irradiation on the release kinetics of APIs are discussed in light of radiation chemical principles. Regulatory aspects pertaining to radiation sterilization of drugs are also considered. Relevant results are summarized in tabular form.

  6. A Fibrous Localized Drug Delivery Platform with NIR-Triggered and Optically Monitored Drug Release.

    PubMed

    Liu, Heng; Fu, Yike; Li, Yangyang; Ren, Zhaohui; Li, Xiang; Han, Gaorong; Mao, Chuanbin

    2016-09-01

    Implantable localized drug delivery systems (LDDSs) with intelligent functionalities have emerged as a powerful chemotherapeutic platform in curing cancer. Developing LDDSs with rationally controlled drug release and real-time monitoring functionalities holds promise for personalized therapeutic protocols but suffers daunting challenges. To overcome such challenges, a series of porous Yb(3+)/Er(3+) codoped CaTiO3 (CTO:Yb,Er) nanofibers, with specifically designed surface functionalization, were synthesized for doxorubicin (DOX) delivery. The content of DOX released could be optically monitored by increase in the intensity ratio of green to red emission (I550/I660) of upconversion photoluminescent nanofibers under 980 nm near-infrared (NIR) excitation owing to the fluorescence resonance energy transfer (FRET) effect between DOX molecules and the nanofibers. More importantly, the 808 nm NIR irradiation enabled markedly accelerated DOX release, confirming representative NIR-triggered drug release properties. In consequence, such CTO:Yb,Er nanofibers presented significantly enhanced in vitro anticancer efficacy under NIR irradiation. This study has thus inspired another promising fibrous LDDS platform with NIR-triggered and optics-monitored DOX releasing for personalized tumor chemotherapy. PMID:27557281

  7. Control of drug loading efficiency and drug release behavior in preparation of hydrophilic-drug-containing monodisperse PLGA microspheres.

    PubMed

    Ito, Fuminori; Fujimori, Hiroyuki; Honnami, Hiroyuki; Kawakami, Hiroyoshi; Kanamura, Kiyoshi; Makino, Kimiko

    2010-05-01

    We prepared monodisperse poly(lactide-co-glycolide) (PLGA) microspheres containing blue dextran (BLD)--a hydrophilic drug--by membrane emulsification technique. The effects of electrolyte addition to the w(2) phase and significance of the droplet size ratio between primary (w(1)/o) and secondary (w(1)/o/w(2)) emulsions during the preparation of these microspheres was examined. The droplet size ratio was evaluated from the effect of stirring rate of the homogenizer when preparing the primary emulsion. The drug loading efficiency of BLD in these microspheres increased with stirring rate. It increased to approximately 90% when 2.0% NaCl was added to the w(2) phase. Drug release from these microspheres was slower than that when they were prepared without electrolyte addition. Despite the very high efficiency drug release was gradual because BLD was distributed at the microspheres core. Relatively monodisperse hydrophilic-drug-containing PLGA microspheres with controlled drug loading efficiency and drug release behavior were prepared. PMID:20221788

  8. Utilizing the protein corona around silica nanoparticles for dual drug loading and release.

    PubMed

    Shahabi, Shakiba; Treccani, Laura; Dringen, Ralf; Rezwan, Kurosch

    2015-10-21

    A protein corona forms spontaneously around silica nanoparticles (SNPs) in serum-containing media. To test whether this protein corona can be utilized for the loading and release of anticancer drugs we incorporated the hydrophilic doxorubicin, the hydrophobic meloxicam as well as their combination in the corona around SNPs. The application of corona-covered SNPs to osteosarcoma cells revealed that drug-free particles did not affect the cell viability. In contrast, SNPs carrying a protein corona with doxorubicin or meloxicam lowered the cell proliferation in a concentration-dependent manner. In addition, these particles had an even greater antiproliferative potential than the respective concentrations of free drugs. The best antiproliferative effects were observed for SNPs containing both doxorubicin and meloxicam in their corona. Co-localization studies revealed the presence of doxorubicin fluorescence in the nucleus and lysosomes of cells exposed to doxorubicin-containing coated SNPs, suggesting that endocytotic uptake of the SNPs facilitates the cellular accumulation of the drug. Our data demonstrate that the protein corona, which spontaneously forms around nanoparticles, can be efficiently exploited for loading the particles with multiple drugs for therapeutic purposes. As drugs are efficiently released from such particles they may have a great potential for nanomedical applications. PMID:26377025

  9. Doxorubicin encapsulated in stealth liposomes conferred with light-triggered drug release.

    PubMed

    Luo, Dandan; Carter, Kevin A; Razi, Aida; Geng, Jumin; Shao, Shuai; Giraldo, Daniel; Sunar, Ulas; Ortega, Joaquin; Lovell, Jonathan F

    2016-01-01

    Stealth liposomes can be used to extend the blood circulation time of encapsulated therapeutics. Inclusion of 2 molar % porphyrin-phospholipid (PoP) imparted optimal near infrared (NIR) light-triggered release of doxorubicin (Dox) from conventional sterically stabilized stealth liposomes. The type and amount of PoP affected drug loading, serum stability and drug release induced by NIR light. Cholesterol and PEGylation were required for Dox loading, but slowed light-triggered release. Dox in stealth PoP liposomes had a long circulation half-life in mice of 21.9 h and was stable in storage for months. Following intravenous injection and NIR irradiation, Dox deposition increased ∼ 7 fold in treated subcutaneous human pancreatic xenografts. Phototreatment induced mild tumor heating and complex tumor hemodynamics. A single chemophototherapy treatment with Dox-loaded stealth PoP liposomes (at 5-7 mg/kg Dox) eradicated tumors while corresponding chemo- or photodynamic therapies were ineffective. A low dose 3 mg/kg Dox phototreatment with stealth PoP liposomes was more effective than a maximum tolerated dose of free (7 mg/kg) or conventional long-circulating liposomal Dox (21 mg/kg). To our knowledge, Dox-loaded stealth PoP liposomes represent the first reported long-circulating nanoparticle capable of light-triggered drug release. PMID:26513413

  10. Effect of mechanical and electrical behavior of gelatin hydrogels on drug release and cell proliferation.

    PubMed

    Biswal, Dibyajyoti; Anupriya, B; Uvanesh, K; Anis, Arfat; Banerjee, Indranil; Pal, Kunal

    2016-01-01

    The present study was aimed to explore the effect of the mechanical and the electrical properties of the gelatin hydrogels on the mammalian cell proliferation and drug release properties. FTIR analysis of the hydrogels suggested that gelatin retained its secondary protein structure. A decrease in the diffusion constant of the water molecules was observed with the increase in the gelatin concentration in the hydrogels. The mechanical and the electrical stabilities of the hydrogels were enhanced with the increase in the gelatin content. Stress relaxation and creep studies were modeled using Weichert and Burger׳s models, respectively. The relaxation time (stress relaxation study) did not follow a concentration-dependent relationship and was found to affect the MG-63 cell (human osteoblast) proliferation. The impedance profile of the hydrogels was modeled using a (RQ)Q model. Release of ciprofloxacin from the hydrogels was inversely dependent on the rate of swelling. The release of the drug was not only dependent on the Fickian diffusion but also on the relaxation process of the gelatin chains. The inhomogeneous constant of the constant phase element representing the hydrogel-electrode interface indicated improved cell proliferation rate with a decrease in the inhomogeneous constant. In gist, the rate of cell proliferation could be related to the relaxation time (stress relaxation) and the inhomogeneous constant of the sample-electrode constant phase element (electrical study) properties, whereas, the drug release properties can be related to the bulk resistance of the formulations. PMID:26327452

  11. A novel drug carrier based on functional modified nanofiber cellulose and the control release behavior

    NASA Astrophysics Data System (ADS)

    Shi, Xiangning; Zheng, Yudong; Zhang, Wei; Zhang, Zeyu; Peng, Yunling

    2013-08-01

    This study developed a novel drug carrier based on functional modified bacterial cellulose(BC) which was conjugated with Ibuprofen(IBU) by esterification. BC-Ibuprofen as the macro- molecular prodrugs and drug carrier used to improve the short half-life of the drug, and was able to control release through the hydrolysis of ester bond between the hydroxyl groups of BC with Ibuprofen under different condition. Fourier transform infrared analysis revealed that Ibuprofen had been successfully grafted onto the bacterial cellulose (BC). Thermal and morphological characterization indicated the formation of the BC-Ibuprofen system incompletely reacted maintained the bulk structure of the pristine material such as crystallinity, 3-dimentional network and so on. The drug release behaviours were affected by the ester bond hydrolysis as well as the microstructure characteristics of the modified nanofiber. The release of BC-IBU showed an apparent pH-dependent, fast in alkaline and acid solution but slow relatively in neutral. Such pH-responsiveness, in addition to its morphological characteristics, in this paper suggested a great potential of BC-IBU as a more effective, safe, and stable prodrug candidate.

  12. Buserelin acetate microparticle dispersion effects drug release and plasma E(1) levels.

    PubMed

    Usami, Makiko; Misawa, Kazumasa; Yagi, Naomi; Sekikawa, Hitoshi; Nabeshima, Toshitaka

    2007-07-18

    We investigated the effect of different dispersion methods on release behavior and efficacy onset following microparticle administration of buserelin acetate (BA) sustained-release injection. In this in vitro release study, the initial dispersion of BA increased with increased stirring speed (p<0.01). Stability of BA was studied over 7 days after BA release. The initial BA release rate was higher (p<0.01) after a 1-min vibration dispersion method (VDM) using a test tube mixer (2000 rpm) compared with the standard dispersion method (SDM) by hand. Without shaking, powder aggregation was observed, and BA release was lower than in either the SDM or VDM methods. In this study using 4-week-old Sprague-Dawley female rats, the initial plasma estrone (E(1)) concentrations were lower (p<0.05) in the VDM method than in the SDM method. Observations by optical microscope and scanning microscope showed no change in microparticle shape or distribution of size induced by SDM, VDM or the ultrasonication dispersion method. These results suggest that different dispersion methods do not change the shape and distribution of microparticle size, but clearly change the BA release rate and the transition in plasma E(1) concentrations that can affect drug efficacy. PMID:17398044

  13. External Cross-linked Mucoadhesive Microbeads for Prolonged Drug Release: Development and In vitro Characterization

    PubMed Central

    Patel, Harshil; Srinatha, A.; Sridhar, B. K.

    2014-01-01

    Mucoadhesive microbeads of low methoxyl pectin were prepared, either alone or in combinations with hydroxypropyl methyl cellulose, sodium carboxymethyl cellulose, methyl cellulose and carbopol 934P, by ionotropic gelation. The influence of copolymers on mucoadhesivity, microbeads characteristics and in vitro drug release was investigated. Spherical microbeads with 78.69±0.59 to 85.84±0.78% drug entrapment and of a size of 791.90±4.58 to 960.88±4.61 μm were prepared. The concentration of cross linking agent affects the encapsulation efficiency of microbeads. Mucoadhesiveness of microbeads was dependent on the concentration of copolymers. The formulations exhibiteda pH-dependent release and followed diffusion-controlled first-order kinetics. PMID:25425758

  14. Controlled release matrix tablets of glipizide: Influence of different grades of ethocel and Co-excipient on drug release.

    PubMed

    Mehsud, Saif Ullah; Khan, Gul Majid; Hussain, Abid; Akram, Muhammad; Akhlaq, Muhammad; Khan, Kamran Ahmad; Shakoor, Abdul

    2016-05-01

    The aim of the current study was to formulate and evaluate glipizide controlled release matrix tablets by means of different grades of polymer Ethoceland different co-excipients in order to evaluate their effect on drug release profiles during in vitro dissolution studies. Type II diabetes mellitus is usually treated with Glipizide. Glipizide belongs to sulfonylurea group. Gastric disturbance and severe hypoglycemia has been observed after taking glipizide orally. To overcome these problems, controlled release matrices were developed using different grades of ethyl cellulose polymer with a drug-polymer ratio of 1:3by the direct compression method. The effect on drug release of partial replacement of lactose by different co-excipients, HPMC K100M, starch and CMC, were also studied. Diameter, thickness, hardness, friability, weight variations, drug contents of formulations were tested, these properties were within prescribed limits. Co-excipients and polymer containing formulations were compared to the without co-excipients and polymer containing formulations with respect to their release profile. After a 24-hour release study, ethyl cellulose polymer containing formulation exhibited prolonged release for 5-16 hours; however the polymer Ethocel (R) standard FP 7 Premium without co-excipient containing formulation exhibited controlled release for 24 hours. Incompatibility was investigated between drugs, co-excipient DSC and polymer study was performed and any type of interaction was not found. Different kinetic models were used to study the release mechanism. An enhanced release rate was observed in case of excipients containing formulations. PMID:27166548

  15. Influence of Drug Properties and Formulation on In Vitro Drug Release and Biowaiver Regulation of Oral Extended Release Dosage Forms.

    PubMed

    Lin, Zhongqiang; Zhou, Deliang; Hoag, Stephen; Qiu, Yihong

    2016-03-01

    Bioequivalence (BE) studies are often required to ensure therapeutic equivalence for major product and manufacturing changes. Waiver of a BE study (biowaiver) is highly desired for such changes. Current regulatory guidelines allow for biowaiver of proportionally similar lower strengths of an extended release (ER) product provided it exhibits similar dissolution to the higher strength in multimedia. The objective of this study is to demonstrate that (1) proportionally similar strengths of ER tablets exhibiting similar in vitro dissolution profiles do not always assure BE and (2) different strengths that do not meet the criteria for dissolution profile similarity may still be bioequivalent. Four marketed ER tablets were used as model drug products. Higher and lower (half) strength tablets were prepared or obtained from commercial source. In vitro drug release was compared using multi-pH media (pH 1.2, 4.5, 6.8) per regulatory guidance. In vivo performance was assessed based on the available in vivo BE data or established in vitro-in vivo relationships. This study demonstrated that the relationship between in vitro dissolution and in vivo performance is complex and dependent on the characteristics of specific drug molecules, product design, and in vitro test conditions. As a result, proportionally similar strengths of ER dosage forms that meet biowaiver requirements per current regulatory guidelines cannot ensure bioequivalence in all cases. Thus, without an established relationship between in vitro and in vivo performance, granting biowaiver based on passing in vitro tests may result in the approval of certain bioinequivalent products, presenting risks to patients. To justify any biowaiver using in vitro test, it is essential to understand the effects of drug properties, formulation design, product characteristics, test method, and its in vivo relevance. Therefore, biowaiver requirements of different strengths of ER dosage forms specified in the current regulatory

  16. Controlled release of photoswitch drugs by degradable polymer microspheres

    PubMed Central

    Groynom, Rebecca; Shoffstall, Erin; Wu, Larry S.; Kramer, Richard H.; Lavik, Erin B.

    2016-01-01

    Background QAQ and DENAQ are synthetic photoswitch compounds that change conformation in response to light, altering current flow through voltage-gated ion channels in neurons. These compounds are drug candidates for restoring light sensitivity in degenerative blinding diseases such as AMD. Purpose However, these photoswitch compounds are cleared from the eye within several days, they must be administered through repeated intravitreal injections. Therefore, we are investigating local, sustained delivery formulations to constantly replenish these molecules and have the potential to restore sight. Methods Here, we encapsulate QAQ and DENAQ into several molecular weights of PLGA through an emulsion technique to assess the viability of delivering the compounds in their therapeutic window over many weeks. We characterize the loading efficiency, release profile, and bioactivity of the compounds after encapsulation. Results A very small burst release was observed for all of the formulations with the majority being delivered over the following two months. The lowest molecular weight PLGA led to the highest loading and most linear delivery for both QAQ and DENAQ. Bioactivity was retained for both compounds across the polymers. Conclusion These results present encapsulation into polymers by emulsion as a viable option for controlled release of QAQ and DENAQ. PMID:26453166

  17. Controlled release of cortisone drugs from block copolymers synthetized by ATRP

    NASA Astrophysics Data System (ADS)

    Valenti, G.; La Carta, S.; Mazzotti, G.; Rapisarda, M.; Perna, S.; Di Gesù, R.; Giorgini, L.; Carbone, D.; Recca, G.; Rizzarelli, P.

    2016-05-01

    Diseases affecting posterior eye segment, like macular edema, infection and neovascularization, may cause visual impairment. Traditional treatments, such as steroidal-drugs intravitreal injections, involve chronic course of therapy usually over a period of years. Moreover, they can require frequent administrations of drug in order to have an adequately disease control. This dramatically reduce patient's compliance. Efforts have been made to develop implantable devices that offer an alternative therapeutic approach to bypass many challenges of conventional type of therapy. Implantable drug delivery systems (DDS) have been developed to optimize therapeutic properties of drugs and ensure their slow release in the specific site. Polymeric materials can play an essential role in modulating drug delivery and their use in such field has become indispensable. During last decades, acrylic polymers have obtained growing interest. Biocompatibility and chemical properties make them extremely versatile, allowing their use in many field such as biomedical. In particular, block methacrylate copolymer with a balance of hydrophilic and hydrophobic properties can be suitable for prolonged DDS in biomedical devices. In this work, we focused on the realization of a system for controlled and long term release of betamethasone 17,21-dipropionate (BDP), a cortisone drug, from methacrylic block copolymers, to be tested in the treatment of the posterior eye's diseases. Different series of methyl methacrylate/hydroxyethyl methacrylate (MMA/HEMA) block and random copolymers, with different monomer compositions (10-60% HEMA), were synthetized by Atom Transfer Radical Polymerization (ATRP) to find the best hydrophilic/hydrophobic ratio, able to ensure optimal kinetic release. Copolymer samples were characterized by NMR spectroscopy (1H-NMR, 13C-NMR, CosY), SEC, TGA and DSC. Monitoring of drug release from films loaded with BDP was carried out by HPLC analysis. Evaluation of different kinetic

  18. Enzyme-responsive nanoparticles for drug release and diagnostics.

    PubMed

    de la Rica, Roberto; Aili, Daniel; Stevens, Molly M

    2012-08-01

    Enzymes are key components of the bionanotechnology toolbox that possess exceptional biorecognition capabilities and outstanding catalytic properties. When combined with the unique physical properties of nanomaterials, the resulting enzyme-responsive nanoparticles can be designed to perform functions efficiently and with high specificity for the triggering stimulus. This powerful concept has been successfully applied to the fabrication of drug delivery schemes where the tissue of interest is targeted via release of cargo triggered by the biocatalytic action of an enzyme. Moreover, the chemical transformation of the carrier by the enzyme can also generate therapeutic molecules, therefore paving the way to design multimodal nanomedicines with synergistic effects. Dysregulation of enzymatic activity has been observed in a number of severe pathological conditions, and this observation is useful not only to program drug delivery in vivo but also to fabricate ultrasensitive sensors for diagnosing these diseases. In this review, several enzyme-responsive nanomaterials such as polymer-based nanoparticles, liposomes, gold nanoparticles and quantum dots are introduced, and the modulation of their physicochemical properties by enzymatic activity emphasized. When known, toxicological issues related to the utilization nanomaterials are highlighted. Key examples of enzyme-responsive nanomaterials for drug delivery and diagnostics are presented, classified by the type of effector biomolecule, including hydrolases such as proteases, lipases and glycosidases, and oxidoreductases. PMID:22266127

  19. Drug structural features affect drug delivery from hyperbranched polyesteramide hot melt extrudates.

    PubMed

    Raviña-Eirin, Elena; Azuaje, Jhonny; Sotelo, Eddy; Gomez-Amoza, Jose Luis; Martinez-Pacheco, Ramon

    2016-05-01

    The aim of this study was firstly to evaluate the utility of Hybrane S1200 as a hot melt extrusion (HME) carrier to prepare instant-release multiparticulate systems for very poorly-soluble drugs such as ketoconazole or nifedipine. Hybrane S1200 allows an easy extrusion of its drug mixtures at a relatively low temperature, not higher than 90°C, and with no need of any additional aid. Extrudates containing 10% of nifedipine or ketoconazole form monophasic systems. Nifedipine extrudate shows no drug release in drug dissolution rate tests while ketoconazole extrudate release reaches only 60% of drug content. Additionally, a turbidity in the dissolution medium due to the formation of a kind of polymer vesicles (ranging 3-0.2μm in size) is observed. These facts could suggest a chemical interaction between the polymer and both drugs, triggered by the HME process. Both nifedipine and ketoconazole share characteristic acid-base profiles that could facilitate a degradation processes within the polymer, thus modifying Hybrane's water-solubility and polar nature. Such modified polymer structure, when in aqueous medium, forms the aforementioned stable vesicles that may encapsulate the drugs, thus making its delivery difficult or even preventing it. PMID:26912462

  20. Design and synthesis of lipidic organoalkoxysilanes for the self-assembly of liposomal nanohybrid cerasomes with controlled drug release properties.

    PubMed

    Liang, Xiaolong; Li, Xiaoda; Jing, Lijia; Xue, Peng; Jiang, Lingdong; Ren, Qiushi; Dai, Zhifei

    2013-11-18

    This paper reports the facile design and synthesis of a series of lipidic organoalkoxysilanes with different numbers of triethoxysilane headgroups and hydrophobic alkyl chains linked by glycerol and pentaerythritol for the construction of cerasomes with regulated surface siloxane density and controlled release behavior. It was found that the number of triethoxysilane headgroups affected the properties of the cerasomes for encapsulation efficiency, drug loading capacity, and release behavior. For both water-soluble doxorubicin (DOX) and water-insoluble paclitaxel (PTX), the release rate from the cerasomes decreased as the number of triethoxysilane headgroups increased. The slower release rate from the cerasomes was attributed to the higher density of the siloxane network on the surface of the cerasomes, which blocks the drug release channels. In contrast to the release results with DOX, the introduction of one more hydrophobic alkyl chain into the cerasome-forming lipid resulted in a slower release rate of PTX from the cerasomes due to the formation of a more compact cerasome bilayer. An MTT viability assay showed that all of these drug-loaded cerasomes inhibited proliferation of the HepG2 cancer cell line. The fine tuning of the chemical structure of the cerasome-forming lipids would foster a new strategy to precisely regulate the release rate of drugs from cerasomes. PMID:24123292

  1. Development of a Cell-Based Bioassay for Phospholipase A2-Triggered Liposomal Drug Release

    PubMed Central

    Arouri, Ahmad; Trojnar, Jakub; Schmidt, Steffen; Hansen, Anders H.; Mollenhauer, Jan; Mouritsen, Ole G.

    2015-01-01

    The feasibility of exploiting secretory phospholipase A2 (sPLA2) enzymes, which are overexpressed in tumors, to activate drug release from liposomes precisely at the tumor site has been demonstrated before. Although the efficacy of the developed formulations was evaluated using in vitro and in vivo models, the pattern of sPLA2-assisted drug release is unknown due to the lack of a suitable bio-relevant model. We report here on the development of a novel bioluminescence living-cell-based luciferase assay for the monitoring of sPLA2-triggered release of luciferin from liposomes. To this end, we engineered breast cancer cells to produce both luciferase and sPLA2 enzymes, where the latter is secreted to the extracellular medium. We report on setting up a robust and reproducible bioassay for testing sPLA2-sensitive, luciferin remote-loaded liposomal formulations, using 1,2-distearoyl-sn-glycero-3-phosphatidylcholine/1,2-distearoyl-sn-glycero-3-phosphatidylglycerol (DSPC/DSPG) 7:3 and DSPC/DSPG/cholesterol 4:3:3 as initial test systems. Upon their addition to the cells, the liposomes were degraded almost instantaneously by sPLA2 releasing the encapsulated luciferin, which provided readout from the luciferase-expressing cells. Cholesterol enhanced the integrity of the formulation without affecting its susceptibility to sPLA2. PEGylation of the liposomes only moderately broadened the release profile of luciferin. The provided bioassay represents a useful tool for monitoring active drug release in situ in real time as well as for testing and optimizing of sPLA2-sensitive lipid formulations. In addition, the bioassay will pave the way for future in-depth in vitro and in vivo studies. PMID:25945937

  2. Lignin content in natural Populus variants affects sugar release

    PubMed Central

    Studer, Michael H.; DeMartini, Jaclyn D.; Davis, Mark F.; Sykes, Robert W.; Davison, Brian; Keller, Martin; Tuskan, Gerald A.; Wyman, Charles E.

    2011-01-01

    The primary obstacle to producing renewable fuels from lignocellulosic biomass is a plant's recalcitrance to releasing sugars bound in the cell wall. From a sample set of wood cores representing 1,100 individual undomesticated Populus trichocarpa trees, 47 extreme phenotypes were selected across measured lignin content and ratio of syringyl and guaiacyl units (S/G ratio). This subset was tested for total sugar release through enzymatic hydrolysis alone as well as through combined hot-water pretreatment and enzymatic hydrolysis using a high-throughput screening method. The total amount of glucan and xylan released varied widely among samples, with total sugar yields of up to 92% of the theoretical maximum. A strong negative correlation between sugar release and lignin content was only found for pretreated samples with an S/G ratio < 2.0. For higher S/G ratios, sugar release was generally higher, and the negative influence of lignin was less pronounced. When examined separately, only glucose release was correlated with lignin content and S/G ratio in this manner, whereas xylose release depended on the S/G ratio alone. For enzymatic hydrolysis without pretreatment, sugar release increased significantly with decreasing lignin content below 20%, irrespective of the S/G ratio. Furthermore, certain samples featuring average lignin content and S/G ratios exhibited exceptional sugar release. These facts suggest that factors beyond lignin and S/G ratio influence recalcitrance to sugar release and point to a critical need for deeper understanding of cell-wall structure before plants can be rationally engineered for reduced recalcitrance and efficient biofuels production. PMID:21444820

  3. Long-term Controlled Drug Release from bi-component Electrospun Fibers

    NASA Astrophysics Data System (ADS)

    Xu, Shanshan; Zhang, Zixin; Xia, Qinghua; Han, Charles

    Multi-drug delivery systems with timed programmed release are hard to be produced due to the complex drug release kinetics which mainly refers to the diffusion of drug molecules from the fiber and the degradation of the carrier. This study focused on the whole life-time story of the long-term drug releasing fibrous systems. Electrospun membrane utilizing FDA approved polymers and broad-spectrum antibiotics showed specific drug release profiles which could be divided into three stages based on the profile slope. With throughout morphology observation, cumulative release amount and releasing duration, releasing kinetics and critical factors were fully discussed during three stages. Through changing the second component, approximately linear drug release profile and a drug release duration about 13 days was prepared, which is perfect for preventing post-operative infection. The addition of this semi-crystalline polymer in turn influenced the fiber swelling and created drug diffusion channels. In conclusion, through adjusting and optimization of the blending component, initial burst release, delayed release for certain duration, and especially the sustained release profile could all be controlled, as well as specific anti-bacterial behavior could be obtained.

  4. Training Personnel for Children Affected by Alcohol or Drugs.

    ERIC Educational Resources Information Center

    Bornfield, Gail; And Others

    This paper presents, first, the statutory entitlement authorizing support to educators of children affected by drugs or alcohol; then, a population overview which covers family characteristics, infant, preschool, and classroom needs; and finally, suggestions for recruitment and retention strategies in personnel training and direct service…

  5. Highly Hydrophilic Luminescent Magnetic Mesoporous Carbon Nanospheres for Controlled Release of Anticancer Drug and Multimodal Imaging.

    PubMed

    Mohapatra, Sasmita; Rout, Smruti R; Das, Rahul K; Nayak, Santoshi; Ghosh, Sudip K

    2016-02-16

    Judicious combination of fluorescence and magnetic properties along with ample drug loading capacity and control release property remains a key challenge in the design of nanotheranostic agents. This paper reports the synthesis of highly hydrophilic optically traceable mesoporous carbon nanospheres which can sustain payloads of the anticancer drug doxorubicin and T2 contrast agent such as cobalt ferrite nanoparticles. The luminescent magnetic hybrid system has been prepared on a mesoporous silica template using a resorcinol-formaldehyde precursor. The mesoporous matrix shows controlled release of the aromatic drug doxorubicin due to disruption of supramolecular π-π interaction at acidic pH. The particles show MR contrast behavior by affecting the proton relaxation with transverse relaxivity (r2) 380 mM(-1) S(-1). The multicolored emission and upconversion luminescence property of our sample are advantageous in bioimaging. In vitro cell experiments shows that the hybrid nanoparticles are endocyted by the tumor cells through passive targeting. The pH-responsive release of doxorubicin presents chemotherapeutic inhibition of cell growth through induction of apoptosis. PMID:26794061

  6. Zn(2+)-Triggered Drug Release from Biocompatible Zirconium MOFs Equipped with Supramolecular Gates.

    PubMed

    Tan, Li-Li; Li, Haiwei; Zhou, Yue; Zhang, Yuanyuan; Feng, Xiao; Wang, Bo; Yang, Ying-Wei

    2015-08-01

    A new theranostic nanoplatform, comprising of monodisperse zirconium metal-organic frameworks (MOFs) as drug carriers and carboxylatopillar[5]arene-based supramolecular switches as gating entities, is constructed, and controlled drug release triggered by bio-friendly Zn(2+) ions (abundant in synaptic vesicles) and auxiliary thermal stimulus is realized. This on-command drug delivery system exhibits large pore sizes for drug encapsulation, excellent biodegradability and biocompatibility, extremely low cytotoxicity and premature drug release, and superior dual-stimuli responsiveness, opening a new avenue in targeted drug delivery and controlled release of therapeutic agents, especially in the treatment of central nervous system diseases. PMID:25919865

  7. Stable Colloidal Drug Aggregates Catch and Release Active Enzymes.

    PubMed

    McLaughlin, Christopher K; Duan, Da; Ganesh, Ahil N; Torosyan, Hayarpi; Shoichet, Brian K; Shoichet, Molly S

    2016-04-15

    Small molecule aggregates are considered nuisance compounds in drug discovery, but their unusual properties as colloids could be exploited to form stable vehicles to preserve protein activity. We investigated the coaggregation of seven molecules chosen because they had been previously intensely studied as colloidal aggregators, coformulating them with bis-azo dyes. The coformulation reduced colloid sizes to <100 nm and improved uniformity of the particle size distribution. The new colloid formulations are more stable than previous aggregator particles. Specifically, coaggregation of Congo Red with sorafenib, tetraiodophenolphthalein (TIPT), or vemurafenib produced particles that are stable in solutions of high ionic strength and high protein concentrations. Like traditional, single compound colloidal aggregates, the stabilized colloids adsorbed and inhibited enzymes like β-lactamase, malate dehydrogenase, and trypsin. Unlike traditional aggregates, the coformulated colloid-protein particles could be centrifuged and resuspended multiple times, and from resuspended particles, active trypsin could be released up to 72 h after adsorption. Unexpectedly, the stable colloidal formulations can sequester, stabilize, and isolate enzymes by spin-down, resuspension, and release. PMID:26741163

  8. Drug-sensing hydrogels for the inducible release of biopharmaceuticals

    NASA Astrophysics Data System (ADS)

    Ehrbar, Martin; Schoenmakers, Ronald; Christen, Erik H.; Fussenegger, Martin; Weber, Wilfried

    2008-10-01

    Drug-dependent dissociation or association of cellular receptors represents a potent pharmacologic mode of action for regulating cell fate and function. Transferring the knowledge of pharmacologically triggered protein-protein interactions to materials science will enable novel design concepts for stimuli-sensing smart hydrogels. Here, we show the design and validation of an antibiotic-sensing hydrogel for the trigger-inducible release of human vascular endothelial growth factor. Genetically engineered bacterial gyrase subunit B (GyrB) (ref. 4) coupled to polyacrylamide was dimerized by the addition of the aminocoumarin antibiotic coumermycin, resulting in hydrogel formation. Addition of increasing concentrations of clinically validated novobiocin (Albamycin) dissociated the GyrB subunits, thereby resulting in dissociation of the hydrogel and dose- and time-dependent liberation of the entrapped protein pharmaceutical VEGF121 for triggering proliferation of human umbilical vein endothelial cells. Pharmacologically controlled hydrogels have the potential to fulfil the promises of stimuli-sensing materials as smart devices for spatiotemporally controlled delivery of drugs within the patient.

  9. INVESTIGATION OF DRUG RELEASE FROM BIODEGRADABLE PLG MICROSPHERES: EXPERIMENT AND THEORY

    SciTech Connect

    ANDREWS, MALCOLM J.; BERCHANE, NADER S.; CARSON, KENNETH H.; RICE-FICHT, ALLISON C.

    2007-01-30

    Piroxicam containing PLG microspheres having different size distributions were fabricated, and in vitro release kinetics were determined for each preparation. Based on the experimental results, a suitable mathematical theory has been developed that incorporates the effect of microsphere size distribution and polymer degradation on drug release. We show from in vitro release experiments that microsphere size has a significant effect on drug release rate. The initial release rate decreased with an increase in microsphere size. In addition, the release profile changed from first order to concave-upward (sigmoidal) as the system size was increased. The mathematical model gave a good fit to the experimental release data.

  10. Comparative evaluation of drug release from aged prolonged polyethylene oxide tablet matrices: effect of excipient and drug type.

    PubMed

    Shojaee, Saeed; Kaialy, Waseem; Cumming, Kenneth Iain; Nokhodchi, Ali

    2016-03-01

    Polyethylene oxide (PEO) undergoes structural adjustments caused by elevated temperatures, which results in loss of its stability within direct compression tablets. The aim of this study was to evaluate the influence of filler solubility on the drug delivery process of matrix tablets containing drugs with different water-solubility properties and stored at elevated temperature. The results demonstrated that in the case of propranolol HCl (highly water-soluble) tablet matrices, soluble lactose promoted drug release, whereas, a stable release of drug was observed with insoluble DCP. A drug release pattern similar to the propranolol HCl formulation containing DCP was obtained for hydrophilic matrix tablets containing either lactose or DCP for the less water-soluble drug, zonisamide. In the case of the partially water-soluble drug, theophylline, formulated with lower molecular weight PEO 750, drug release increased considerably in the presence of both fillers with increasing storage time, however a stable release rate (similar to fresh samples) was observed in the case of higher molecular weight PEO 303 tablet matrices containing theophylline with either lactose or DCP. The hydration properties (e.g. solubility) of the diluents had a considerable effect on drug release behavior from various model matrices; this effect was dependent on both molecular weight of PEO and solubility of drug. PMID:25410967

  11. Measure your septa release ratios: pheromone release ratio variability affected by rubber septa and solvent

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The type of solvent and volume of the solvent used to load pheromone/volatile components onto rubber septa had significant effects on release ratios, the variability of those release ratios, and the recoverability of the volatile components during subsequent extraction with hexane. Volatile release ...

  12. Synthetic Zeolites as Controlled-Release Delivery Systems for Anti-Inflammatory Drugs.

    PubMed

    Khodaverdi, Elham; Soleimani, Hossein Ali; Mohammadpour, Fatemeh; Hadizadeh, Farzin

    2016-06-01

    Scientists have always been trying to use artificial zeolites to make modified-release drug delivery systems in the gastrointestinal tract. An ideal carrier should have the capability to release the drug in the intestine, which is the main area of absorption. Zeolites are mineral aluminosilicate compounds with regular structure and huge porosity, which are available in natural and artificial forms. In this study, soaking, filtration and solvent evaporation methods were used to load the drugs after activation of the zeolites. Weight measurement, spectroscopy FTIR, thermogravimetry and scanning electronic microscope were used to determine drug loading on the systems. Finally, consideration of drug release was made in a simulated gastric fluid and a simulated intestinal fluid for all matrixes (zeolites containing drugs) and drugs without zeolites. Diclofenac sodium (D) and piroxicam (P) were used as the drug models, and zeolites X and Y as the carriers. Drug loading percentage showed that over 90% of drugs were loaded on zeolites. Dissolution tests in stomach pH environment showed that the control samples (drug without zeolite) released considerable amount of drugs (about 90%) within first 15 min when it was about 10-20% for the matrixes. These results are favorable as NSAIDs irritate the stomach wall and it is ideal not to release much drugs in the stomach. Furthermore, release rate of drugs from matrixes has shown slower rate in comparison with control samples in intestine pH environment. PMID:26705687

  13. Effect of carboxymethylation on rheological and drug release characteristics of locust bean gum matrix tablets.

    PubMed

    Chakravorty, Amrita; Barman, Gouranga; Mukherjee, Sudipta; Sa, Biswanath

    2016-06-25

    This study was undertaken to investigate correlation between the carboxymethylation-induced rheological changes and drug release characteristics of locust bean gum (LBG) matrix tablets. LBG was derivatized to carboxymethyl LBG (CMLBG) and characterized by (13)C NMR, FTIR and elemental analyses. Rheological studies revealed that LBG, in contact with water, produced a strong elastic gel which swelled less due to lower penetration of water resulting in slower drug release. On the other hand, CMLBG formed a viscous polymer solution through which higher influx of water resulted in rapid swelling of the matrix and faster drug release. Although the release from a particular matrix was dependent on drugs' solubilities, CMLBG matrix tablet produced faster release of all the drugs than LBG matrix tablets. In conclusion, rheological study appeared to be an useful tool to predict release of drugs from polysaccharide matrix tablets. PMID:27083792

  14. 21 CFR 500.26 - Timed-release dosage form drugs.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... release the active ingredients over a prolonged period of time. There is a possibility of unsafe... this form, which are referred to by such terms as timed-release, controlled-release, prolonged-release.... (c) The fact that the labeling of this kind of drug may claim delayed, prolonged, controlled,...

  15. 21 CFR 500.26 - Timed-release dosage form drugs.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... release the active ingredients over a prolonged period of time. There is a possibility of unsafe... this form, which are referred to by such terms as timed-release, controlled-release, prolonged-release.... (c) The fact that the labeling of this kind of drug may claim delayed, prolonged, controlled,...

  16. 21 CFR 500.26 - Timed-release dosage form drugs.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... release the active ingredients over a prolonged period of time. There is a possibility of unsafe... this form, which are referred to by such terms as timed-release, controlled-release, prolonged-release.... (c) The fact that the labeling of this kind of drug may claim delayed, prolonged, controlled,...

  17. 21 CFR 500.26 - Timed-release dosage form drugs.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... release the active ingredients over a prolonged period of time. There is a possibility of unsafe... this form, which are referred to by such terms as timed-release, controlled-release, prolonged-release.... (c) The fact that the labeling of this kind of drug may claim delayed, prolonged, controlled,...

  18. Localized drug delivery using crosslinked gelatin gels containing liposomes: factors influencing liposome stability and drug release.

    PubMed

    DiTizio, V; Karlgard, C; Lilge, L; Khoury, A E; Mittelman, M W; DiCosmo, F

    2000-07-01

    We describe a drug-delivery vehicle that combines the sustained release properties of liposomes with the structural advantages of crosslinked gelatin gels that can be implanted directly or coated onto medical devices. Liposome inclusion in gelatin gels does not compromise thermal stability nor does it interfere with the resiliency of gels to tensile force. However, electron spin resonance analysis of sequestered DPPC liposomes revealed a slight depression (ca. 1.0 degrees C) of the gel-to-fluid phase transition relative to liposomes in suspension. The level of liposome release from gels was determined by liposome concentration, liposome size, and the presence of poly(ethylene oxide) chains in the gel matrix or in the liposome membrane. Both neutral and charged liposomes displayed relatively high affinities for poly(ethylene glycol)gelatin gels, with only 10-15% release of initially sequestered liposomes while liposomes in which poly(ethylene glycol) was included within the membrane were not as well retained (approximately 65% release). The in vitro efflux of ciprofloxacin from liposomal gels immersed in serum was nearly complete after 24 h compared to 38% release of liposomal chlorhexidine after 6 days. The serum-induced destabilization of liposomal ciprofloxacin depended on the accessibility of serum components to gels as partly immersed gels retained approximately 50% of their load of drug after 24 h. In vivo experiments using a catheterized rabbit model of urinary tract infection revealed the absence of viable Escherichia coli on coated catheter surfaces in seven out of nine cases while all untreated catheter surfaces examined (n = 7) were contaminated. PMID:10813750

  19. Olive oil phenolic compounds affect the release of aroma compounds.

    PubMed

    Genovese, Alessandro; Caporaso, Nicola; Villani, Veronica; Paduano, Antonello; Sacchi, Raffaele

    2015-08-15

    Twelve aroma compounds were monitored and quantified by dynamic headspace analysis after their addition in refined olive oil model systems with extra virgin olive oil (EVOO) biophenols to simulate EVOO aroma. The influence of polyphenols on aroma release was studied under simulated mouth conditions by using human saliva, and SPME-GC/MS analysis. While few differences were observed in orthonasal assay (without saliva), interesting results were obtained for retronasal aroma. Biophenols caused generally the lowest headspace release of almost all volatile compounds. However, only ethyl esters and linalool concentrations were significantly lower in retronasal than orthonasal assay. Saliva also caused higher concentration of hexanal, probably due to hydroperoxide lyase (HPL) action on linoleyl hydroperoxides. Epicatechin was compared to EVOO phenolics and the behaviour was dramatically different, likely to be due to salivary protein-tannin binding interactions, which influenced aroma headspace release. These results were also confirmed using two extra virgin olive oils. PMID:25794752

  20. Iron Deprivation Affects Drug Susceptibilities of Mycobacteria Targeting Membrane Integrity

    PubMed Central

    Pal, Rahul; Hameed, Saif; Fatima, Zeeshan

    2015-01-01

    Multidrug resistance (MDR) acquired by Mycobacterium tuberculosis (MTB) through continuous deployment of antitubercular drugs warrants immediate search for novel targets and mechanisms. The ability of MTB to sense and become accustomed to changes in the host is essential for survival and confers the basis of infection. A crucial condition that MTB must surmount is iron limitation, during the establishment of infection, since iron is required by both bacteria and humans. This study focuses on how iron deprivation affects drug susceptibilities of known anti-TB drugs in Mycobacterium smegmatis, a “surrogate of MTB.” We showed that iron deprivation leads to enhanced potency of most commonly used first line anti-TB drugs that could be reverted upon iron supplementation. We explored that membrane homeostasis is disrupted upon iron deprivation as revealed by enhanced membrane permeability and hypersensitivity to membrane perturbing agent leading to increased passive diffusion of drug and TEM images showing detectable differences in cell envelope thickness. Furthermore, iron seems to be indispensable to sustain genotoxic stress suggesting its possible role in DNA repair machinery. Taken together, we for the first time established a link between cellular iron and drug susceptibility of mycobacteria suggesting iron as novel determinant to combat MDR. PMID:26779346

  1. Dissolution and drug release profiles of phosphate glasses doped with high valency oxides.

    PubMed

    El-Meliegy, E; Farag, M M; Knowles, J C

    2016-06-01

    This paper investigates phosphate glasses incorporating vanadium and molybdenum oxides for effective management of dissolution and drug release. These glass formulations are found to reduce the rate of dissolution from the glass surfaces. The drug functional groups of vancomycin molecules loaded by immersion showed stronger hydrogen bonding with Vanadium doped glasses and consequently lower rate of drug release over 2 weeks indicating better surface attachment with the drug molecules and slow drug release profiles. This can be explained by the strong adherence of drug molecules to glass surfaces compared with the molybdenum containing glasses (PM5 and PM10). The strong attachment relates to hydrogen bonding between the amino-functional groups of vancomycin and the hydrated P-O-H groups in the glass network. In conclusion, the rate of dissolution of doped glasses and the rate of drug release can be administered to deliver the drug molecules over weeks. PMID:27117794

  2. Swelling/floating capability and drug release characterizations of gastroretentive drug delivery system based on a combination of hydroxyethyl cellulose and sodium carboxymethyl cellulose.

    PubMed

    Chen, Ying-Chen; Ho, Hsiu-O; Liu, Der-Zen; Siow, Wen-Shian; Sheu, Ming-Thau

    2015-01-01

    The aim of this study was to characterize the swelling and floating behaviors of gastroretentive drug delivery system (GRDDS) composed of hydroxyethyl cellulose (HEC) and sodium carboxymethyl cellulose (NaCMC) and to optimize HEC/NaCMC GRDDS to incorporate three model drugs with different solubilities (metformin, ciprofloxacin, and esomeprazole). Various ratios of NaCMC to HEC were formulated, and their swelling and floating behaviors were characterized. Influences of media containing various NaCl concentrations on the swelling and floating behaviors and drug solubility were also characterized. Finally, release profiles of the three model drugs from GRDDS formulation (F1-4) and formulation (F1-1) were examined. Results demonstrated when the GRDDS tablets were tested in simulated gastric solution, the degree of swelling at 6 h was decreased for each formulation that contained NaCMC in comparison to those in de-ionized water (DIW). Of note, floating duration was enhanced when in simulated gastric solution compared to DIW. Further, the hydration of tablets was found to be retarded as the NaCl concentration in the medium increased resulting in smaller gel layers and swelling sizes. Dissolution profiles of the three model drugs in media containing various concentrations of NaCl showed that the addition of NaCl to the media affected the solubility of the drugs, and also their gelling behaviors, resulting in different mechanisms for controlling a drug's release. The release mechanism of the freely water-soluble drug, metformin, was mainly diffusion-controlled, while those of the water-soluble drug, ciprofloxacin, and the slightly water-soluble drug, esomeprazole, were mainly anomalous diffusion. Overall results showed that the developed GRDDS composed of HEC 250HHX and NaCMC of 450 cps possessed proper swelling extents and desired floating periods with sustained-release characteristics. PMID:25617891

  3. Swelling and erosion of pectin matrix tablets and their impact on drug release behavior.

    PubMed

    Sriamornsak, Pornsak; Thirawong, Nartaya; Weerapol, Yossanun; Nunthanid, Jurairat; Sungthongjeen, Srisagul

    2007-08-01

    The aim of this study was to investigate swelling and erosion behaviors of hydrophilic matrix tablets using pectin and their impact on drug release. The matrix tablets were prepared by direct compression using different types of pectin. Swelling and erosion studies of pectin matrix tablets were carried out in various media. The pectin matrix tablets formed a continuous gel layer while in contact with the aqueous medium undergoing a combination of swelling and erosion. The swelling action of pectin matrices was controlled by the rate of its hydration in the medium. Release studies showed that the swelling and erosion of matrices influenced the drug release. The extent of matrix swelling, erosion and diffusion of drug determined the kinetics as well as mechanism of drug release from pectin-based matrix tablets. The release data showed a good fit into the power law or the Korsmeyer-Peppas equation indicating the combined effect of diffusion and erosion mechanisms of drug release. PMID:17267193

  4. Introduction of a mathematical model for optimizing the drug release in the patient’s body

    PubMed Central

    2014-01-01

    Background Drug release in a patient’s body is of particular interest to the pharmaceutical industry. One of the most essential types of drug release is the gradual release based on a behavior, which is called a profile or modified release. The investigation of the time-oriented quality characteristic is one of the newest topics in the area of product design. There are already several approaches addressing this issue. In this paper, a mathematical model is proposed to find the suitable values of the controllable factors in a drug to achieve the profile of the drug release in the patient’s body. Results The proposed method has several advantages over the existing methods. Conclusion The authors feel that by adjusting the control factors during the production process the drug release profile become closer to the reference profile. PMID:24386961

  5. How to easily provide zero order release of freely soluble drugs from coated pellets.

    PubMed

    Dekyndt, B; Verin, J; Neut, C; Siepmann, F; Siepmann, J

    2015-01-15

    Coated pellets offer a great potential as controlled drug delivery systems. However, constant drug release rates are difficult to achieve with this type of dosage forms if the drug is freely water-soluble. This is because diffusional mass transport generally plays a major role and with time the drug concentration within the system decreases, resulting in decreased concentration gradients, which are the driving forces for drug release. Thus, generally "curve-shaped" release profiles with monotonically decreasing slopes are observed. This type of release kinetics might be inappropriate for an efficient and safe drug treatment. Despite the great practical importance of this potentially crucial formulation challenge, surprisingly little is yet known on how to effectively address it. In this study, a novel approach is presented based on sequential layers of drug and polymer (initially free of drug) to provide a non-homogeneous initial drug distribution, combined with lag-time effects, and partial initial drug diffusion towards the pellet's core. Sugar and microcrystalline cellulose beads were used as starter cores, metoprolol succinate as freely soluble drug, ethylcellulose, and poly(vinyl acetate) as release rate controlling polymers. The type, number, thickness, and sequence of the drug and polymer layers were varied. Interestingly, a rather simple four layer system (two drug and two polymer layers) allowed providing about constant drug release during 8h. Compared to previously proposed coated pellets aiming at constant release of freely water-soluble drugs based on non-homogeneous initial drug distribution, the total coating level in this study was very much reduced: to only about 20%. Hence, the suggested formulation approach is relatively simple and can help overcoming a potentially major hurdle in practice. Its applicability has also been demonstrated for another type of drug: propranolol hydrochloride. PMID:25445976

  6. Evaluation of Factors Affecting Powdered Drug Reconstitution in Microgravity

    NASA Technical Reports Server (NTRS)

    Schaffner, Grant; Johnston, Smith; Marshburn, Tom

    1999-01-01

    standard pharmacological supplies. The experiment included a parametric assessment of possible factors affecting the reconstitution process. The specific questions that we wished to answer were: (1) Is it possible to reconstitute powdered drugs in weightlessness using standard pharmacological equipment? (2) What are the differences between drug reconstitution in a 1-G and a 0-G environment? (3) What techniques of mixing the drug powder and diluent are more successful? (4) What physical and chemical factors play a role in determining the success of mixing and dissolution? (5) Is it necessary to employ crewmember and equipment restraints during the reconstitution process?

  7. Quantitative ToF-SIMS studies of protein drug release from biodegradable polymer drug delivery membranes

    NASA Astrophysics Data System (ADS)

    Burns, Sarah A.; Gardella, Joseph A.

    2008-12-01

    Biodegradable polymers are of interest in developing strategies to control protein drug delivery. The protein that was used in this study is Keratinocyte Growth Factor (KGF) which is a protein involved in the re-epithelialization process. The protein is stabilized in the biodegradable polymer matrix during formulation and over the course of polymer degradation with the use of an ionic surfactant Aerosol-OT (AOT) which will encapsulate the protein in an aqueous environment. The release kinetics of the protein from the surface of these materials requires precise timing which is a crucial factor in the efficacy of this drug delivery system. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) was used in the same capacity to identify the molecular ion peak of the surfactant and polymer and use this to determine surface concentration. In the polymer matrix, the surfactant molecular ion peak was observed in the positive and negative mode at m/ z 467 and 421, respectively. These peaks were determined to be [AOT + Na +] and [AOT - Na +]. These methods are used to identify the surfactant and protein from the polymer matrix and are used to measure the rate of surface accumulation. The second step was to compare this accumulation rate with the release rate of the protein into an aqueous solution during the degradation of the biodegradable film. This rate is compared to that from fluorescence spectroscopy measurements using the protein autofluorescence from that released into aqueous solution [C.M. Mahoney, J. Yu, A. Fahey, J.A.J. Gardella, SIMS depth profiling of polymer blends with protein based drugs, Appl. Surf. Sci. 252 (2006), 6609-6614.].

  8. Pickering w/o emulsions: drug release and topical delivery.

    PubMed

    Frelichowska, Justyna; Bolzinger, Marie-Alexandrine; Valour, Jean-Pierre; Mouaziz, Hanna; Pelletier, Jocelyne; Chevalier, Yves

    2009-02-23

    The skin absorption from Pickering emulsions as a new dosage form was investigated for the first time. Pickering emulsions are stabilized by adsorbed solid particles instead of emulsifier molecules. They are promising dosage forms that significantly differ from classical emulsions within several features. The skin permeation of a hydrophilic model penetrant (caffeine) was investigated from a w/o Pickering emulsion and compared to a w/o classical emulsion stabilized with an emulsifier. Both emulsions had the same composition and physicochemical properties in order to focus on the effect of the interfacial layer on the drug release and skin absorption processes. The highest permeation rates were obtained from the Pickering emulsion with a pseudo-steady state flux of 25 microg cm(-2)h(-1), threefold higher than from a classical emulsion (9.7 microg cm(-2)h(-1)). After 24h exposure, caffeine was mostly in the receptor fluid and in the dermis; cumulated amounts of caffeine were higher for the Pickering emulsion. Several physicochemical phenomena were investigated for clearing up the mechanisms of enhanced permeation from the Pickering emulsion. Among them, higher adhesion of Pickering emulsion droplets to skin surface was disclosed. The transport of caffeine adsorbed on silica particles was also considered relevant since skin stripping showed that aggregates of silica particles entered deeply the stratum corneum. PMID:18992799

  9. Simultaneous quantification of drug release and erosion from hypromellose hydrophilic matrices.

    PubMed

    Ghori, Muhammad U; Ginting, Gidion; Smith, Alan M; Conway, Barbara R

    2014-04-25

    Hypromellose, HPMC, is frequently used to control drug release from matrix tablet formulations. Drug is released by a combination of diffusion through and erosion of, the matrix and is usually measured invitro by separate dissolution and swelling/erosion studies. The present study was designed to measure matrix erosion, polymer dissolution and drug release kinetics and their inter-relationship in a single experiment using a phenol-sulphuric acid assay to quantify dissolved HPMC alongside spectrophotometrical analysis of drug release. HPMC-based matrix tablets were manufactured containing two drugs at various drug:HPMC ratios. Drug release was determined and the degree of erosion was calculated by gravimetry. Results showed the matrix erosion rate and drug release were dependent on HPMC content and drug solubility, as expected. It was also apparent that the erosion rate was directly related to the drug release kinetics and comparative analysis of both matrix erosion techniques showed a high level of correlation. The findings show that a simple and inexpensive assay can be utilised not only to quantify HPMC but can also be used to calculate the degree of erosion of tablet matrices, negating the need for a separate study and providing a simplified practical approach that may be of use during product optimization. PMID:24560637

  10. Thermo-responsive hydrogels with N-isopropylacrylamide/acrylamide interpenetrating networks for controlled drug release.

    PubMed

    Jiang, Yu; Wu, Yanye; Huo, Yinlei

    2015-01-01

    Series of thermo-sensitive hydrogels (PNAs) based on N-isopropylacrylamide/acrylamide interpenetrating polymer networks were synthesized via in situ free-radical polymerization. Poly (ethylene glycol diacrylate) and poly (ε-caprolactone diacrylate) were synthesized as macro-cross-linkers due to their excellent biocompatibilities. The macro-cross-linkers and hydrogels were characterized by (1)H NMR and FT-IR, respectively. The interior morphology of the hydrogels was observed by scanning electron microscopy. The swelling ratios at different temperatures and the swelling/deswelling kinetics of the hydrogels were studied. Their volume phase transition temperatures were also measured by differential scanning calorimetry characterization. The results indicated that the PNA hydrogels had uniform macroporous structures, and they not only had considerable swelling ratios, but also exhibited rapid swelling/deswelling kinetics and response sensitivities. In addition, the weight ratio of AAm/NIPAAm also affected the swelling performance and phase transition temperature of hydrogels, and its value less than 5% was the optimal proportion to achieve excellent comprehensive properties. Levofloxacin lactate and Naproxen were selected as drugs and simulated in vitro condition release, and the drug release results showed that the PNA hydrogels behaved fast release performance. PMID:26146984

  11. Monitoring pH-Triggered Drug Release from Radioluminescent Nanocapsules with X-Ray Excited Optical Luminescence

    PubMed Central

    Chen, Hongyu; Moore, Thomas; Qi, Bin; Colvin, Daniel C.; Jelen, Erika K.; Hitchcock, Dale A.; He, Jian; Mefford, O. Thompson; Gore, John C.; Alexis, Frank; Anker, Jeffrey N.

    2013-01-01

    One of the greatest challenges in cancer therapy is to develop methods to deliver chemotherapy agents to tumor cells while reducing systemic toxicity to non-cancerous cells. A promising approach to localizing drug release is to employ drug-loaded nanoparticles with coatings that release the drugs only in the presence of specific triggers found in the target cells such as pH, enzymes, or light. However, many parameters affect the nanoparticle distribution and drug release rate and it is difficult to quantify drug release in situ. In this work, we show proof of principle for a “smart” radioluminescent nanocapsule with X-ray excited optical luminescence (XEOL) spectrum that changes during release of the optically absorbing chemotherapy drug, doxorubicin. XEOL provides an almost background-free luminescent signal for measuring drug release from particles irradiated by a narrow X-ray beam. We study in vitro pH triggered release rates of doxorubicin from nanocapsules coated with a pH responsive polyelectrolyte multilayer using HPLC and XEOL spectroscopy. The doxorubicin was loaded to over 5 % by weight, and released from the capsule with a time constant in vitro of ~ 36 days at pH 7.4, and 21.4 hr at pH 5.0, respectively. The Gd2O2S:Eu nanocapsules are also paramagnetic at room temperature with similar magnetic susceptibility and similarly good MRI T2 relaxivities to Gd2O3, but the sulfur increases the radioluminescence intensity and shifts the spectrum. Empty nanocapsules did not affect cell viability up to concentrations of at least 250 μ/ml. These empty nanocapsules accumulated in a mouse liver and spleen following tail vein injection, and could be observed in vivo using XEOL. The particles are synthesized with a versatile template synthesis technique which allows for control of particle size and shape. The XEOL analysis technique opens the door to non-invasive quantification of drug release as a function of nanoparticle size, shape, surface chemistry and tissue

  12. Monitoring pH-triggered drug release from radioluminescent nanocapsules with X-ray excited optical luminescence.

    PubMed

    Chen, Hongyu; Moore, Thomas; Qi, Bin; Colvin, Daniel C; Jelen, Erika K; Hitchcock, Dale A; He, Jian; Mefford, O Thompson; Gore, John C; Alexis, Frank; Anker, Jeffrey N

    2013-02-26

    One of the greatest challenges in cancer therapy is to develop methods to deliver chemotherapy agents to tumor cells while reducing systemic toxicity to noncancerous cells. A promising approach to localizing drug release is to employ drug-loaded nanoparticles with coatings that release the drugs only in the presence of specific triggers found in the target cells such as pH, enzymes, or light. However, many parameters affect the nanoparticle distribution and drug release rate, and it is difficult to quantify drug release in situ. In this work, we show proof-of-principle for a "smart" radioluminescent nanocapsule with an X-ray excited optical luminescence (XEOL) spectrum that changes during release of the optically absorbing chemotherapy drug, doxorubicin. XEOL provides an almost background-free luminescent signal for measuring drug release from particles irradiated by a narrow X-ray beam. We study in vitro pH-triggered release rates of doxorubicin from nanocapsules coated with a pH-responsive polyelectrolyte multilayer using HPLC and XEOL spectroscopy. The doxorubicin was loaded to over 5% by weight and released from the capsule with a time constant in vitro of ∼36 days at pH 7.4 and 21 h at pH 5.0, respectively. The Gd₂O₂S:Eu nanocapsules are also paramagnetic at room temperature with similar magnetic susceptibility and similarly good MRI T₂ relaxivities to Gd₂O₃, but the sulfur increases the radioluminescence intensity and shifts the spectrum. Empty nanocapsules did not affect cell viability up to concentrations of at least 250 μg/mL. These empty nanocapsules accumulated in a mouse liver and spleen following tail vein injection and could be observed in vivo using XEOL. The particles are synthesized with a versatile template synthesis technique which allows for control of particle size and shape. The XEOL analysis technique opens the door to noninvasive quantification of drug release as a function of nanoparticle size, shape, surface chemistry, and

  13. Cross-linked high amylose starch derivatives as matrices for controlled release of high drug loadings.

    PubMed

    Mulhbacher, J; Ispas-Szabo, P; Lenaerts, V; Mateescu, M A

    2001-09-11

    Selection of hydrogels as excipients in controlled drug release systems depends on the characteristics of the gel and of the drug. Three types of derivatives were synthesized from cross-linked high amylose starch (HASCL-6) by substitution of hydroxylic groups with cationic (carboxymethyl: CM), anionic (aminoethyl: AE) and acetate (Ac) groups. These new polymeric excipients are able to control the release over 20 h from monolithic tablets loaded with 20 to 60% drug. Three drugs were used as model tracer: acetaminophen (uncharged), acetylsalicylic acid (having an acidic group) and metformin (having a basic group). It was found that the release of ionic drugs from CM-HASCL-6 and AE-HASCL-6 matrices can be partially controlled by ionic interaction between pendant groups of polymer and drugs. The substitution degree of HASCL-6 derivatives can also be varied to modulate the drug's release time. These derivatives represent a novel generation of pharmaceutical excipients, recommended for high loading dosage formulations. PMID:11532312

  14. Swelling/Floating Capability and Drug Release Characterizations of Gastroretentive Drug Delivery System Based on a Combination of Hydroxyethyl Cellulose and Sodium Carboxymethyl Cellulose

    PubMed Central

    Chen, Ying-Chen; Ho, Hsiu-O; Liu, Der-Zen; Siow, Wen-Shian; Sheu, Ming-Thau

    2015-01-01

    The aim of this study was to characterize the swelling and floating behaviors of gastroretentive drug delivery system (GRDDS) composed of hydroxyethyl cellulose (HEC) and sodium carboxymethyl cellulose (NaCMC) and to optimize HEC/NaCMC GRDDS to incorporate three model drugs with different solubilities (metformin, ciprofloxacin, and esomeprazole). Various ratios of NaCMC to HEC were formulated, and their swelling and floating behaviors were characterized. Influences of media containing various NaCl concentrations on the swelling and floating behaviors and drug solubility were also characterized. Finally, release profiles of the three model drugs from GRDDS formulation (F1-4) and formulation (F1-1) were examined. Results demonstrated when the GRDDS tablets were tested in simulated gastric solution, the degree of swelling at 6 h was decreased for each formulation that contained NaCMC in comparison to those in de-ionized water (DIW). Of note, floating duration was enhanced when in simulated gastric solution compared to DIW. Further, the hydration of tablets was found to be retarded as the NaCl concentration in the medium increased resulting in smaller gel layers and swelling sizes. Dissolution profiles of the three model drugs in media containing various concentrations of NaCl showed that the addition of NaCl to the media affected the solubility of the drugs, and also their gelling behaviors, resulting in different mechanisms for controlling a drug’s release. The release mechanism of the freely water-soluble drug, metformin, was mainly diffusion-controlled, while those of the water-soluble drug, ciprofloxacin, and the slightly water-soluble drug, esomeprazole, were mainly anomalous diffusion. Overall results showed that the developed GRDDS composed of HEC 250HHX and NaCMC of 450 cps possessed proper swelling extents and desired floating periods with sustained-release characteristics. PMID:25617891

  15. Robust and stimuli-responsive POSS hybrid PDMAEMA hydrogels for controlled drug release.

    PubMed

    Chen, Yi; Zeng, Guangsheng; Liu, Wenyong

    2016-09-01

    A new polyhedral oligomeric silsesquioxane (POSS) hybrid hydrogels were desinged and fabricated by introducing cationic octa-ammonium (Oa)-POSS) into chemically cross-linked cationic PDMAEMA hydrogels via in situ radical freezing polymerization. The prepared gels (shorten as OP-PD gels) show considerably improved properties through the effective incorporation and dispersion of Oa-POSS particles in gels. Comparing to the Oa-POSS-free gels, the hybrid gels own better mechanical properties with higher tensile and compressive strength. Meantime, except the decreased swelling ratio in acid condition, the OP-PD gels still keep excellent swelling ability with obvious pH and temperature double responsiveness, which is affected by the content of Oa-POSS slightly. All OP-PD gels exhibit an ultrarapid deswelling rate due to the interconnected micropores structure caused by freezing and the formation of microhydrophobic region around POSS particles. Moreover, the application potential of OP-PD gels in drug release was exploited by using flutamide as target drug, the result showed that the increased Oa-POSS could improve the drug loading ability, and OP-PD gels showed well controlled-release effect in simulated human stomachic condition. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2345-2355, 2016. PMID:27149531

  16. Composite poly(vinyl alcohol)/poly(vinyl acetate) electrospun nanofibrous mats as a novel wound dressing matrix for controlled release of drugs

    PubMed Central

    Jannesari, Marziyeh; Varshosaz, Jaleh; Morshed, Mohammad; Zamani, Maedeh

    2011-01-01

    The aim of this study was to develop novel biomedicated nanofiber electrospun mats for controlled drug release, especially drug release directly to an injury site to accelerate wound healing. Nanofibers of poly(vinyl alcohol) (PVA), poly(vinyl acetate) (PVAc), and a 50:50 composite blend, loaded with ciprofloxacin HCl (CipHCl), were successfully prepared by an electrospinning technique for the first time. The morphology and average diameter of the electrospun nanofibers were investigated by scanning electron microscopy. X-ray diffraction studies indicated an amorphous distribution of the drug inside the nanofiber blend. Introducing the drug into polymeric solutions significantly decreased solution viscosities as well as nanofiber diameter. In vitro drug release evaluations showed that both the kind of polymer and the amount of drug loaded greatly affected the degree of swelling, weight loss, and initial burst and rate of drug release. Blending PVA and PVAc exhibited a useful and convenient method for electrospinning in order to control the rate and period of drug release in wound healing applications. Also, the thickness of the blend nanofiber mats strongly influenced the initial release and rate of drug release. PMID:21720511

  17. Drugs, detention, and death: a study of the mortality of recently released prisoners.

    PubMed

    Krinsky, Clarissa S; Lathrop, Sarah L; Brown, Pamela; Nolte, Kurt B

    2009-03-01

    It has been theorized that drug abusers recently released from prison have an increased risk of fatal drug overdose. The objective of this study was to determine whether persons released from prison in the state of New Mexico have an increased risk of death due to unintentional drug overdose in the time immediately after release from prison. A total of 96 people were identified who had been released from prison and subsequently suffered an unnatural death in 2001 through 2003. Among those who had drug-caused deaths, there was a significantly increased risk of dying in the first 2 weeks after release versus the subsequent 10 weeks RR = 3.08 (P < 0.001, 95% CI: 1.83-5.16). For those who died in the first 2 months after release, there was an increased risk of fatal drug overdose compared with dying of other unnatural causes (P = 0.025). Of those who died of fatal drug overdoses within the first 2 months, the average incarceration time was significantly longer than those who lived longer than 2 months after release (P = 0.021) and they were more likely to have used opiates (P < 0.0001) and sedatives (P = 0.01). Prisoners are at an increased risk of a fatal unintentional drug overdose immediately after release. The time surrounding release provides an opportunity for education on the risks of accidental overdose and the development of interventions to mitigate these risks. PMID:19237844

  18. 3D Printing of Medicines: Engineering Novel Oral Devices with Unique Design and Drug Release Characteristics.

    PubMed

    Goyanes, Alvaro; Wang, Jie; Buanz, Asma; Martínez-Pacheco, Ramón; Telford, Richard; Gaisford, Simon; Basit, Abdul W

    2015-11-01

    Three dimensional printing (3D printing) was used to fabricate novel oral drug delivery devices with specialized design configurations. Each device was loaded with multiple actives, with the intent of applying this process to the production of personalized medicines tailored at the point of dispensing or use. A filament extruder was used to obtain drug-loaded--paracetamol (acetaminophen) or caffeine--filaments of poly(vinyl alcohol) with characteristics suitable for use in fused-deposition modeling 3D printing. A multinozzle 3D printer enabled fabrication of capsule-shaped solid devices containing the drug with different internal structures. The design configurations included a multilayer device, with each layer containing drug, whose identity was different to the drug in the adjacent layers, and a two-compartment device comprising a caplet embedded within a larger caplet (DuoCaplet), with each compartment containing a different drug. Raman spectroscopy was used to collect 2-dimensional hyper spectral arrays across the entire surface of the devices. Processing of the arrays using direct classical least-squares component matching to produce false color representations of distribution of the drugs was used. This clearly showed a definitive separation between the drug layers of paracetamol and caffeine. Drug release tests in biorelevant bicarbonate media showed unique drug release profiles dependent on the macrostructure of the devices. In the case of the multilayer devices, release of both paracetamol and caffeine was simultaneous and independent of drug solubility. With the DuoCaplet design, it was possible to engineer either rapid drug release or delayed release by selecting the site of incorporation of the drug in the device; the lag-time for release from the internal compartment was dependent on the characteristics of the external layer. The study confirms the potential of 3D printing to fabricate multiple-drug containing devices with specialized design

  19. Changes in the drug release pattern of fresh and set simvastatin-loaded brushite cement.

    PubMed

    Mestres, Gemma; Kugiejko, Karol; Pastorino, David; Unosson, Johanna; Öhman, Caroline; Karlsson Ott, Marjam; Ginebra, Maria-Pau; Persson, Cecilia

    2016-01-01

    Calcium phosphate cements are synthetic bone graft substitutes able to set at physiological conditions. They can be applied by minimally invasive surgery and can also be used as drug delivery systems. Consequently, the drug release pattern from the cement paste (fresh cement) is of high clinical interest. However, previous studies have commonly evaluated the drug release using pre-set cements only. Therefore, the aim of this work was to determine if the time elapsed from cement preparation until immersion in the solution (3 min for fresh cements, and 1h and 15 h for pre-set cements) had an influence on its physical properties, and correlating these to the drug release profile. Simvastatin was selected as a model drug, while brushite cement was used as drug carrier. This study quantified how the setting of a material reduces the accessibility of the release media to the material, thus preventing drug release. A shift in the drug release pattern was observed, from a burst-release for fresh cements to a sustained release for pre-set cements. PMID:26478290

  20. Modulating drug release from gastric-floating microcapsules through spray-coating layers.

    PubMed

    Lee, Wei Li; Tan, Jun Wei Melvin; Tan, Chaoyang Nicholas; Loo, Say Chye Joachim

    2014-01-01

    Floating dosage forms with prolonged gastric residence time have garnered much interest in the field of oral delivery. However, studies had shown that slow and incomplete release of hydrophobic drugs during gastric residence period would reduce drug absorption and cause drug wastage. Herein, a spray-coated floating microcapsule system was developed to encapsulate fenofibrate and piroxicam, as model hydrophobic drugs, into the coating layers with the aim of enhancing and tuning drug release rates. Incorporating fenofibrate into rubbery poly(caprolactone) (PCL) coating layer resulted in a complete and sustained release for up to 8 h, with outermost non-drug-holding PCL coating layer serving as a rate-controlling membrane. To realize a multidrug-loaded system, both hydrophilic metformin HCl and hydrophobic fenofibrate were simultaneously incorporated into these spray-coated microcapsules, with metformin HCl and fenofibrate localized within the hollow cavity of the capsule and coating layer, respectively. Both drugs were observed to be completely released from these coated microcapsules in a sustained manner. Through specific tailoring of coating polymers and their configurations, piroxicam loaded in both the outer polyethylene glycol and inner PCL coating layers was released in a double-profile manner (i.e. an immediate burst release as the loading dose, followed by a sustained release as the maintenance dose). The fabricated microcapsules exhibited excellent buoyancy in simulated gastric fluid, and provided controlled and sustained release, thus revealing its potential as a rate-controlled oral drug delivery system. PMID:25470374

  1. Reversible morphology transitions of supramolecular polymer self-assemblies for switch-controlled drug release.

    PubMed

    Zhang, Haitao; Fan, Xiaodong; Suo, Rongtian; Li, Hui; Yang, Zhen; Zhang, Wanbin; Bai, Yang; Yao, Hao; Tian, Wei

    2015-10-28

    A novel method for switch-controlled drug release was developed through the reversible morphology transitions of supramolecular branched copolymer self-assemblies. The reversible transitions from vesicles to nanoparticles were successfully achieved by alternating UV and visible light irradiation to obtain morphology-controlled drug release in a switch mode. PMID:26343347

  2. Rheological characterization and drug release studies of gum exudates of Terminalia catappa Linn.

    PubMed

    Kumar, Sadhis V; Sasmal, Dinakar; Pal, Subodh C

    2008-01-01

    The present study was undertaken to evaluate the gum exudates of Terminalia catappa Linn. (TC gum) as a release retarding excipient in oral controlled drug delivery system. The rheological properties of TC gum were studied and different formulation techniques were used to evaluate the comparative drug release characteristics. The viscosity was found to be dependent on concentration and pH. Temperature up to 60 degrees C did not show significant effect on viscosity. The rheological kinetics evaluated by power law, revealed the shear thinning behavior of the TC gum dispersion in water. Matrix tablets of TC gum were prepared with the model drug dextromethorphan hydrobromide (DH) by direct compression, wet granulation and solid dispersion techniques. The dissolution profiles of the matrix tablets were compared with the pure drug containing capsules using the USP Basket apparatus with 500 ml phosphate buffer of pH 6.8 as a dissolution medium. The drug release from the compressed tablets containing TC gum was comparatively sustained than pure drug containing capsules. Even though all the formulation techniques showed reduction of dissolution rate, aqueous wet granulation showed the maximum sustained release of more than 8 h. The release kinetics estimated by the power law revealed that the drug release mechanism involved in the dextromethorphan matrix is anomalous transport as indicated by the release exponent n values. Thus the study confirmed that the TC gum might be used in the controlled drug delivery system as a release-retarding polymer. PMID:18661243

  3. Modulating Drug Release from Gastric-Floating Microcapsules through Spray-Coating Layers

    PubMed Central

    Tan, Chaoyang Nicholas; Loo, Say Chye Joachim

    2014-01-01

    Floating dosage forms with prolonged gastric residence time have garnered much interest in the field of oral delivery. However, studies had shown that slow and incomplete release of hydrophobic drugs during gastric residence period would reduce drug absorption and cause drug wastage. Herein, a spray-coated floating microcapsule system was developed to encapsulate fenofibrate and piroxicam, as model hydrophobic drugs, into the coating layers with the aim of enhancing and tuning drug release rates. Incorporating fenofibrate into rubbery poly(caprolactone) (PCL) coating layer resulted in a complete and sustained release for up to 8 h, with outermost non-drug-holding PCL coating layer serving as a rate-controlling membrane. To realize a multidrug-loaded system, both hydrophilic metformin HCl and hydrophobic fenofibrate were simultaneously incorporated into these spray-coated microcapsules, with metformin HCl and fenofibrate localized within the hollow cavity of the capsule and coating layer, respectively. Both drugs were observed to be completely released from these coated microcapsules in a sustained manner. Through specific tailoring of coating polymers and their configurations, piroxicam loaded in both the outer polyethylene glycol and inner PCL coating layers was released in a double-profile manner (i.e. an immediate burst release as the loading dose, followed by a sustained release as the maintenance dose). The fabricated microcapsules exhibited excellent buoyancy in simulated gastric fluid, and provided controlled and sustained release, thus revealing its potential as a rate-controlled oral drug delivery system. PMID:25470374

  4. EXPANDED STARCH AS A FLOATING DOSAGE MATRIX FOR THE CONTROLLED RELEASE OF MODEL DRUG COMPOUNDS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Starch-based materials were tested using model drug compounds to determine the feasibility of using starch as an oral floating dosage matrix. Oral controlled release systems require increased bio-availability, predictable release rates, and site-specific delivery. Starch and model drugs were compo...

  5. Preparation and drug controlled-release of polyion complex micelles as drug delivery systems.

    PubMed

    Luo, Yali; Yao, Xinjian; Yuan, Jinfang; Ding, Tao; Gao, Qingyu

    2009-02-01

    Block copolymers, poly(N-vinylprrolidone)-block-poly(styrene-alter-maleic anhydride) (PVP-b-PSMA) and poly(N-vinylprrolidone)-block-poly(N,N-dimethylaminoethyl methacrylate) (PVP-b-PDMAEMA), were synthesized by reversible addition- fragmentation chain transfer (RAFT) polymerization. In aqueous media, this a pair of oppositely-charged diblock copolymers could self-assemble into stable and narrow distribution polyion complex micelles (PICMs). Transmission electron micrographs (TEM) and dynamic light scattering (DLS) analysis showed that the micelles to be spherically shaped with mean hydrodynamic diameter around 70nm. In addition, the PICMs display ability to response to external stimuli. All of theses features are quite feasible for utilizing it as a novel intelligent drug delivery system. In order to assess its application in biomedical area, release profiles of coenzyme A (Co A) from PICMs were studied under both simulated gastric and intestinal pH conditions. The release was much quicker in pH 7.4 buffer than in pH 2.0 solution. Based on these results, these PICMs could be a potential pH-sensitive carrier for colon-specific drug delivery system. PMID:19124231

  6. Factors affecting the development of adverse drug reactions (Review article)

    PubMed Central

    Alomar, Muaed Jamal

    2013-01-01

    Objectives To discuss the effect of certain factors on the occurrence of Adverse Drug Reactions (ADRs). Data Sources A systematic review of the literature in the period between 1991 and 2012 was made based on PubMed, the Cochrane database of systematic reviews, EMBASE and IDIS. Key words used were: medication error, adverse drug reaction, iatrogenic disease factors, ambulatory care, primary health care, side effects and treatment hazards. Summary Many factors play a crucial role in the occurrence of ADRs, some of these are patient related, drug related or socially related factors. Age for instance has a very critical impact on the occurrence of ADRs, both very young and very old patients are more vulnerable to these reactions than other age groups. Alcohol intake also has a crucial impact on ADRs. Other factors are gender, race, pregnancy, breast feeding, kidney problems, liver function, drug dose and frequency and many other factors. The effect of these factors on ADRs is well documented in the medical literature. Taking these factors into consideration during medical evaluation enables medical practitioners to choose the best drug regimen. Conclusion Many factors affect the occurrence of ADRs. Some of these factors can be changed like smoking or alcohol intake others cannot be changed like age, presence of other diseases or genetic factors. Understanding the different effects of these factors on ADRs enables healthcare professionals to choose the most appropriate medication for that particular patient. It also helps the healthcare professionals to give the best advice to patients. Pharmacogenomics is the most recent science which emphasizes the genetic predisposition of ADRs. This innovative science provides a new perspective in dealing with the decision making process of drug selection. PMID:24648818

  7. Factors influencing the erosion rate and the drug release kinetics from organogels designed as matrices for oral controlled release of a hydrophobic drug.

    PubMed

    Pereira Camelo, Sarah Regina; Franceschi, Sophie; Perez, Emile; Girod Fullana, Sophie; Ré, Maria Inês

    2016-06-01

    This article proposes solid-like systems from sunflower oil structured with a fibrillar network built by the assembly of 12-hydroxystearic acid (12-HSA), a gelator molecule for an oil phase. The resulting organogels were studied as oral controlled release formulations for a lipophilic drug, Efavirenz (EFV), dissolved in the oil. The effects of the gelator concentration on the thermal properties of the organogels were studied by Differential Scanning Calorimetry (DSC) and showed that drug incorporation did not change the sol-gel-sol transitions. The erosion and drug release kinetics from organogels under conventional (filling gelatin capsules) or multiparticulate (beads obtained by prilling) dosage forms were measured in simulated gastric and intestinal fluids. EFV release profiles were analyzed using model-dependent (curve-fitting) and independent approaches (Dissolution Efficiency DE). Korsmeyer-Peppas was the best fitting release kinetic model based on the goodness of fit, revealing a release mechanism from organogels loaded with EFV different from the simple drug diffusion release mechanism obtained from oily formulations. From organogels, EFV probably diffuses through an outer gel layer that erodes releasing oil droplets containing dissolved EFV into the aqueous medium. PMID:26548427

  8. Towards elucidation of the drug release mechanism from compressed hydrophilic matrices made of cellulose ethers. III. Critical use of thermodynamic parameters of activation for modeling the water penetration and drug release processes.

    PubMed

    Ferrero, Carmen; Massuelle, Danielle; Jeannerat, Damien; Doelker, Eric

    2013-09-10

    The two main purposes of this work were: (i) to critically consider the use of thermodynamic parameters of activation for elucidating the drug release mechanism from hydroxypropyl methylcellulose (HPMC) matrices, and (ii) to examine the effect of neutral (pH 6) and acidic (pH 2) media on the release mechanism. For this, caffeine was chosen as model drug and various processes were investigated for the effect of temperature and pH: caffeine diffusion in solution and HPMC gels, and drug release from and water penetration into the HPMC tablets. Generally, the kinetics of the processes was not significantly affected by pH. As for the temperature dependence, the activation energy (E(a)) values calculated from caffeine diffusivities were in the range of Fickian transport (20-40 kJ mol⁻¹). Regarding caffeine release from HPMC matrices, fitting the profiles using the Korsmeyer-Peppas model would indicate anomalous transport. However, the low apparent E(a) values obtained were not compatible with a swelling-controlled mechanism and can be assigned to the dimensional change of the system during drug release. Unexpectedly, negative apparent E(a) values were calculated for the water uptake process, which can be ascribed to the exothermic dissolution of water into the initially dry HPMC, the expansion of the matrix and the polymer dissolution. Taking these contributions into account, the true E(a) would fall into the range valid for Fickian diffusion. Consequently, a relaxation-controlled release mechanism can be dismissed. The apparent anomalous drug release from HPMC matrices results from a coupled Fickian diffusion-erosion mechanism, both at pH 6 and 2. PMID:23727289

  9. A novel study on the mechanisms of drug release in PLGA-mPEG microspheres with fluorescent drug.

    PubMed

    Shi, Chen; Feng, Shuibin; Liu, Ping; Liu, Xianzhe; Feng, Xiaobo; Fu, Dehao

    2016-06-01

    The purpose of this research was to proof the microspheres release mechanism by a novel method-detecting and comparing the drugs fluorescent changes on the microspheres surface. Fluorescein sodium (FS, 0.4 kDa) and fluorescein isothiocyanate-bovine serum albumin (FITC-BSA, 66.8 kDa) were employed as model drugs. FS and FITC-BSA were encapsulated into PLGA-mPEG microspheres through double emulsion evaporation method, and the drug-loaded microspheres in vitro degradation and release behaviors were evaluated by scanning electron microscope, gel permeation chromatography, confocal laser scanning microscopy (CLSM), BCA assay kit, and UV-vis spectrophotometry. FS-loaded microspheres revealed a severe initial burst release, followed by a sustained release, and we could observe a bright fluorescent on the microspheres surface during the early release period under the CLSM. The bright fluorescent gradually faded out in the later period as only 1~2% FS was remained after 14 days release. FITC-BSA-loaded microspheres revealed a typical tri-phase release profile, and we observed a weak fluorescent on the microspheres surface after the initial burst release, and the fluorescent came bright again after an obvious erosion appeared on the microspheres surface. In the later release stage, the fluorescent gradually faded out as the fast release of FITC-BSA. PMID:26980344

  10. High-amylose carboxymethyl starch matrices for oral sustained drug-release: in vitro and in vivo evaluation.

    PubMed

    Nabais, T; Brouillet, F; Kyriacos, S; Mroueh, M; Amores da Silva, P; Bataille, B; Chebli, C; Cartilier, L

    2007-03-01

    High-amylose corn starch, that contains 70% of amylose chains and 30% of amylopectin, has been used to obtain substituted amylose (SA) polymers. Tablets have been prepared by direct compression, i.e. dry mixing of drug and SA, followed by compression, which is the easiest way to manufacture an oral dosage form. Until now, their controlled-release properties have been assessed only by an in vitro dissolution test. Amylose-based polymers are normally subject to biodegradation by alpha-amylase enzymes present in the gastrointestinal tract, but matrix systems show no significant degradation of tablets by alpha-amylase in vitro. High-amylose sodium carboxymethyl starch (HASCA) is an interesting excipient for sustained drug-release in solid oral dosage forms. In addition to the easy manufacture of tablets by direct compression, the results show that in vitro drug-release from an optimized HASCA formulation is not affected by either acidic pH value or acidic medium residence time. In addition, a compressed blend of HASCA with an optimized quantity of sodium chloride provides a pharmaceutical sustained-release tablet with improved integrity for oral administration. In vivo studies demonstrate extended drug absorption, showing that the matrix tablets do not disintegrate immediately. Nevertheless, acetaminophen does not seem to be the most appropriate drug for this type of formulation. PMID:17275270

  11. Controlled drug release from melt-extrudates through processing parameters: a chemometric approach.

    PubMed

    Sarraf, Abraham G; Cherkaoui, Samir; Jordan, Olivier; Gurny, Robert; Doelker, Eric

    2015-03-15

    The objective of this study was to tailor a drug release profile through the adjustment of some key processing parameters involved in melt-extrusion: die temperature, shear rate, die length and drug particle size. Two experimental designs were selected, namely a 2-level full factorial design to examine the effects and significance of the processing factors, and a central composite design of the surface responses to find the best set of factor levels to obtain given specifications of drug release. Extrudates of poly(ethylene-co-vinyl acetate) and phenylpropanolamine hydrochloride were prepared using a ram extruder. Drug release profiles from the matrix systems were fitted using a power law, for which a new mathematical expression of a burst release was provided. The burst release and exponent were selected as the responses. The processing factors had a drastic influence on the drug release. Within the domain that was investigated, the burst release and the exponent varied from 6 to 54% and 0.1 to 0.4, respectively, resulting in a time requires for 50% drug release extending from hours to weeks. These results demonstrated the possibilities of modulating the release profile by means of the processing parameters rather than through the classical approach of altering the formulation. PMID:25543111

  12. Drug release kinetics and fronts movement studies from methyl methacrylate (MMA) copolymer matrix tablets: effect of copolymer type and matrix porosity.

    PubMed

    Ferrero, C; Bravo, I; Jiménez-Castellanos, M R

    2003-09-19

    Several methyl methacrylate (MMA) copolymers have recently been proposed as an alternative for the formulation of controlled-release matrix tablets. Copolymers were synthesised by free radical copolymerisation of methyl methacrylate with starch or cellulose derivatives and were alternatively dried by oven or freeze-drying techniques. Both the chemical composition and the drying technique were demonstrated to have a considerable influence on the physical properties of the copolymers. The present investigation was focused on the elucidation of the drug release mechanism from MMA copolymer matrices, using anhydrous theophylline as model drug. Drug release experiments were performed from free tablets. Radial drug release and fronts movement were also evaluated using special devices consisting of two Plexiglass discs joined by means of four stainless steel screws. Mathematical analysis of release data was performed using Higuchi, Korsmeyer and Peppas equations and fronts movement was investigated using a colorimetric technique. The drug release rate and the relative positions of the fronts were studied as functions of the type of copolymer and the initial porosity of the tablets. Drug release was controlled mainly by diffusion and the release rate was found to be affected by the drying method and related to the area exposed to the dissolution medium. Three distinct fronts (water uptake, complete wetting, erosion) were observed during the release process and the dynamics of fronts movement confirmed the diffusional mechanism. PMID:14499186

  13. Novel sustained release, swellable and bioadhesive gastroretentive drug delivery system for ofloxacin.

    PubMed

    Chavanpatil, Mahesh D; Jain, Paras; Chaudhari, Sachin; Shear, Rajesh; Vavia, Pradeep R

    2006-06-19

    Oral sustained release gastroretentive dosage forms offer many advantages for drugs having absorption from upper gastrointestinal tract and improve the bioavailability of medications that are characterized by a narrow absorption window. A new gastroretentive sustained release delivery system was developed with floating, swellable and bioadhesive properties. All these properties were optimized and evaluated. Various release retarding polymers like psyllium husk, HPMC K100M and a swelling agent, crosspovidone in combinations were tried and optimized to get the release profile for 24 h. Formulations were evaluated for in vitro drug release profile, swelling characteristics and in vitro bioadhesion property. The in vitro drug release followed Higuchi kinetics and the drug release mechanism was found to be of anomalous or non-Fickian type. For the developed formulation, the value of n was found to be 0.5766 while for the marketed formulation the value was 0.5718 indicating the anomalous transport. The high water uptake leading to higher swelling of the tablet supported the anomalous release mechanism of ofloxacin. The similarity factor f2 was found to be 91.12 for the developed formulation indicating the release was similar to that of the marketed formulation (Zanocin OD). The swelling properties were increased with increasing crosspovidone concentration and contributed significantly in drug release from the tablet matrix. The bioadhesive property of the developed formulation was found to be significant (P < 0.005) in combination as compared to HPMC K100M and psyllium husk alone. PMID:16567072

  14. Cellulose crosslinked pH-responsive polyurethanes for drug delivery: α-hydroxy acids as drug release modifiers.

    PubMed

    Solanki, Archana; Thakore, Sonal

    2015-09-01

    Cellulose crosslinked waterborne polyurethanes (PUs) based on poly ɛ-caprolactone with lactic acid/glycolic acid/dimethylol-propionic acid as a drug release modifiers cum chain extenders were prepared. PUs were loaded with felodipine and drug release was monitored at different pH values. The structure of the polymers was characterized by FTIR, DSC & TGA and SEM. The encapsulation of dug inside PU matrix and the morphology of polymer after drug release were studied by using SEM. All the PUs were observed to degrade under highly basic conditions. The PUs act as pH sensitive drug carriers with an added advantage of modulated release rate as a function of acid chain extenders. The rate of release of the drug was significantly faster at pH 7.4 as compared to gastric pH 1.2, with same incubation time. The PUs reported in the present study may be suitable for medical applications like vaginal drug delivery and colon specific drug delivery. PMID:26188306

  15. Reduction-Responsive Polymeric Micelles and Vesicles for Triggered Intracellular Drug Release

    PubMed Central

    Sun, Huanli; Cheng, Ru; Deng, Chao

    2014-01-01

    Abstract Significance: The therapeutic effects of current micellar and vesicular drug formulations are restricted by slow and inefficient drug release at the pathological site. The development of smart polymeric nanocarriers that release drugs upon arriving at the target site has received a tremendous amount of attention for cancer therapy. Recent Advances: Taking advantage of a high reducing potential in the tumor tissues and in particular inside the tumor cells, various reduction-sensitive polymeric micelles and vesicles have been designed and explored for triggered anticancer drug release. These reduction-responsive nanosystems have demonstrated several unique features, such as good stability under physiological conditions, fast response to intracellular reducing environment, triggering drug release right in the cytosol and cell nucleus, and significantly improved antitumor activity, compared to traditional reduction-insensitive counterparts. Critical Issues: Although reduction-sensitive micelles and polymersomes have accomplished rapid intracellular drug release and enhanced in vitro antitumor effect, their fate inside the cells including the mechanism, site, and rate of reduction reaction remains unclear. Moreover, the systemic fate and performance of reduction-sensitive polymeric drug formulations have to be investigated. Future Directions: Biophysical studies should be carried out to gain insight into the degradation and drug release behaviors of reduction-responsive nanocarriers inside the tumor cells. Furthermore, novel ligand-decorated reduction-sensitive nanoparticulate drug formulations should be designed and explored for targeted cancer therapy in vivo. Antioxid. Redox Signal. 21, 755–767. PMID:24279980

  16. Triggered drug release from superhydrophobic meshes using high-intensity focused ultrasound.

    PubMed

    Yohe, Stefan T; Kopechek, Jonathan A; Porter, Tyrone M; Colson, Yolonda L; Grinstaff, Mark W

    2013-09-01

    Application of high-intensity focused ultrasound to drug-loaded superhydrophobic meshes affords triggered drug release by displacing an entrapped air layer. The air layer within the superhydrophobic meshes is characterized using direct visualization and B-mode imaging. Drug-loaded superhydrophobic meshes are cytotoxic in an in vitro assay after ultrasound treatment. PMID:23592698

  17. Triggered Drug Release from Superhydrophobic Meshes using High-Intensity Focused Ultrasound

    PubMed Central

    Yohe, Stefan T.; Kopechek, Jonathan A.; Porter, Tyrone M.; Colson, Yolonda L.

    2014-01-01

    Application of high-intensity focused ultrasound to drug-loaded superhydrophobic meshes affords triggered drug release by displacing an entrapped air layer. The air layer within the superhydrophobic meshes is characterized using direct visualization and B-mode imaging. Drug-loaded superhydrophobic meshes are cytotoxic in an in vitro assay after ultrasound treatment. PMID:23592698

  18. Controlled release drug coatings on flexible neural probes.

    PubMed

    Mercanzini, Andre; Reddy, Sai; Velluto, Diana; Colin, Philippe; Maillard, Anne; Bensadoun, Jean-Charles; Bertsch, Arnaud; Hubbell, Jeffrey A; Renaud, Philippe

    2007-01-01

    We present the development, characterization and in vivo validation of a novel drug eluting coating that has been applied to flexible neural probes. The coating consists of drug eluting nanoparticles loaded with an anti-inflammatory drug embedded in a biodegradable polymer. The drug eluting coating is applied to flexible polymer neural probes with platinum electrodes. The drug eluting device is implanted in one hemisphere of a rat, while a control device is implanted in the opposite hemisphere. Impedance measurements are performed to determine the effect of the drug eluting coating on the tissue reaction surrounding the probe and the electrical characteristics of the devices. Probes that are coated with drug eluting coatings show better long term impedance characteristics over control probes. These coatings can be used to increase the reliability and long term success of neural prostheses. PMID:18003541

  19. Multidrug PLA-PEG filomicelles for concurrent delivery of anticancer drugs-The influence of drug-drug and drug-polymer interactions on drug loading and release properties.

    PubMed

    Jelonek, Katarzyna; Li, Suming; Kaczmarczyk, Bożena; Marcinkowski, Andrzej; Orchel, Arkadiusz; Musiał-Kulik, Monika; Kasperczyk, Janusz

    2016-08-20

    This study aimed to analyze the influence of drug-drug and drug-polymer interactions on drug loading and release properties of multidrug micelles. Three hydrophobic drugs-paclitaxel (Ptx), 17-AAG and rapamycin (Rap) were incorporated in poly(l-lactide)-poly(ethylene glycol) (PLA-PEG) filomicelles. Double loaded micelles containing Ptx and 17-AAG were used for the sake of comparison. (1)H NMR confirmed the effective incorporation of the various drugs in micelles, and HPLC allowed to determine the drug loading contents. FTIR was used to evaluate interactions between particular drugs and between drugs and copolymer. Ptx and 17-AAG present similar loading efficiencies in double loaded micelles probably due to interactions of drugs with each other and also with the copolymer. In contrast, unequal drug loading properties are observed for triple loaded micelles. Rapamycin shows very weak interactions with the copolymer, and displays the lowest loading efficiency. In vitro release of drugs from micelles was realized in pH 7.4 phosphate buffered saline at 37°C, and monitored by HPLC. Similar release profiles are observed for the three drugs: a strong burst followed by slower release. Nevertheless, Ptx release from micelles is significantly slower as compared to 17-AAG and Rap, probably due to interactions of NH and OH groups of Ptx with the carbonyl group of PLA. In vitro cytotoxicity of Ptx/17-AAG/Rap loaded micelles and a mixture of free drugs was determined. Drug loaded micelles exhibit advantageous effect of prolonged drug release and cytotoxic activity against Caco-2 cells, which makes them a promising solution for simultaneous drug delivery to solid tumors. Therefore, understanding of interactions within multidrug micelles should be a valuable approach for the development of concurrent delivery systems of anticancer drugs with tailored properties. PMID:27346726

  20. Characterization of drug-release kinetics in trabecular bone from titania nanotube implants

    PubMed Central

    Aw, Moom Sinn; Khalid, Kamarul A; Gulati, Karan; Atkins, Gerald J; Pivonka, Peter; Findlay, David M; Losic, Dusan

    2012-01-01

    Purpose The aim of this study was to investigate the application of the three-dimensional bone bioreactor for studying drug-release kinetics and distribution of drugs in the ex vivo cancellous bone environment, and to demonstrate the application of nanoengineered titanium (Ti) wires generated with titania nanotube (TNT) arrays as drug-releasing implants for local drug delivery Methods Nanoengineered Ti wires covered with a layer of TNT arrays implanted in bone were used as a drug-releasing implant. Viable bovine trabecular bone was used as the ex vivo bone substrate embedded with the implants and placed in the bone reactor. A hydrophilic fluorescent dye (rhodamine B) was used as the model drug, loaded inside the TNT–Ti implants, to monitor drug release and transport in trabecular bone. The distribution of released model drug in the bone was monitored throughout the bone structure, and concentration profiles at different vertical (0–5 mm) and horizontal (0–10 mm) distances from the implant surface were obtained at a range of release times from 1 hour to 5 days. Results Scanning electron microscopy confirmed that well-ordered, vertically aligned nanotube arrays were formed on the surface of prepared TNT–Ti wires. Thermogravimetric analysis proved loading of the model drug and fluorescence spectroscopy was used to show drug-release characteristics in-vitro. The drug release from implants inserted into bone ex vivo showed a consistent gradual release of model drug from the TNT–Ti implants, with a characteristic three-dimensional distribution into the surrounding bone, over a period of 5 days. The parameters including the flow rate of bone culture medium, differences in trabecular microarchitecture between bone samples, and mechanical loading were found to have the most significant influence on drug distribution in the bone. Conclusion These results demonstrate the utility of the Zetos™ system for ex vivo drug-release studies in bone, which can be applied to

  1. Controlled drug release from pellets containing water-insoluble drugs dissolved in a self-emulsifying system.

    PubMed

    Serratoni, Mauro; Newton, Michael; Booth, Steven; Clarke, Ashley

    2007-01-01

    The aim of the study was to provide a controlled release system, which could be used for the oral administration of highly water-insoluble drugs. Pellets have been prepared by extrusion/spheronization containing two model drugs (methyl and propyl parabens) of low water solubility. One type of pellets contained the drugs mixed with lactose and microcrystalline cellulose (MCC) and the other types of pellets contained the model drugs dissolved in a self-emulsifying system (4.8%) consisting of equal parts of mono-diglycerides and polysorbate 80 and MCC. Pellets of all types in the same size fraction (1.4-2.0 mm) were coated to different levels of weight gain, with ethylcellulose, talc and glycerol. A sample of pellets containing methyl parabens in the self-emulsifying system was pre-coated with a film of hydroxypropylmethyl cellulose from an aqueous solution and then coated as above. Dissolution experiments established that the presence of the self-emulsifying system enhanced the drug release of both model drugs and that the film coating considerably reduced the drug release from pellets made with just water, lactose and MCC. The coating reduced the drug release from the pellets containing the self-emulsifying system to a lesser extent but in relation to the quantity of coat applied to the pellets. The application of a sub-coating of hydroxypropylmethyl cellulose was able to reduce the release rate of methyl parabens self-emulsifying system ethyl cellulose coated pellets. Thus, the formulation approach offers the possibility of formulating and controlling the in vitro release of water-insoluble drugs from solid oral dosage forms. PMID:17056237

  2. Gene duplication and divergence affecting drug content in Cannabis sativa.

    PubMed

    Weiblen, George D; Wenger, Jonathan P; Craft, Kathleen J; ElSohly, Mahmoud A; Mehmedic, Zlatko; Treiber, Erin L; Marks, M David

    2015-12-01

    Cannabis sativa is an economically important source of durable fibers, nutritious seeds, and psychoactive drugs but few economic plants are so poorly understood genetically. Marijuana and hemp were crossed to evaluate competing models of cannabinoid inheritance and to explain the predominance of tetrahydrocannabinolic acid (THCA) in marijuana compared with cannabidiolic acid (CBDA) in hemp. Individuals in the resulting F2 population were assessed for differential expression of cannabinoid synthase genes and were used in linkage mapping. Genetic markers associated with divergent cannabinoid phenotypes were identified. Although phenotypic segregation and a major quantitative trait locus (QTL) for the THCA/CBDA ratio were consistent with a simple model of codominant alleles at a single locus, the diversity of THCA and CBDA synthase sequences observed in the mapping population, the position of enzyme coding loci on the map, and patterns of expression suggest multiple linked loci. Phylogenetic analysis further suggests a history of duplication and divergence affecting drug content. Marijuana is distinguished from hemp by a nonfunctional CBDA synthase that appears to have been positively selected to enhance psychoactivity. An unlinked QTL for cannabinoid quantity may also have played a role in the recent escalation of drug potency. PMID:26189495

  3. Mineralization, biodegradation, and drug release behavior of gelatin/apatite composite microspheres for bone regeneration.

    PubMed

    Leeuwenburgh, Sander C G; Jo, Junichiro; Wang, Huanan; Yamamoto, Masaya; Jansen, John A; Tabata, Yasuhiko

    2010-10-11

    Gelatin microspheres are well-known for their capacity to release growth factors in a controlled manner, but gelatin microspheres do not calcify in the absence of so-called bioactive substances that induce deposition of calcium phosphate (CaP) bone mineral. This study has investigated if CaP nanocrystals can be incorporated into gelatin microspheres to render these inert microspheres bioactive without compromising the drug releasing properties of gelatin microspheres. Incorporation of CaP nanocrystals into gelatin microspheres resulted into reduced biodegradation and drug release rates, whereas their calcifying capacity increased strongly compared to inert gelatin microspheres. The reduced drug release rate was correlated to the reduced degradation rate as caused by a physical cross-linking effect of CaP nanocrystals dispersed in the gelatin matrix. Consequently, these composite microspheres combine beneficial drug-releasing properties of organic gelatin with the calcifying capacity of a dispersed CaP phase. PMID:20804200

  4. Starch-free grewia gum matrices: Compaction, swelling, erosion and drug release behaviour.

    PubMed

    Nep, E I; Asare-Addo, K; Ghori, M U; Conway, B R; Smith, A M

    2015-12-30

    Polysaccharides are suitable for application as hydrophilic matrices because of their ability to hydrate and swell upon contact with fluids, forming a gel layer which controls drug release. When extracted from plants, polysaccharides often contain significant quantities of starch that impacts upon their functional properties. This study aimed to evaluate differences in swelling, erosion and drug release from matrix tablets prepared from grewia gum (GG) and starch-free grewia gum (GDS) extracted from the stems of Grewia mollis. HPMC was used as a control polymer with theophylline as a model drug. Swelling, erosion, and in-vitro release were performed in deionized water, pH 1.2 and pH 6.8 media. The Vergnaud and Krosmeyer-Peppas model were used for swelling and drug release kinetics, respectively. However, linear regression technique was used to determine the erosion rate. GDS compacts were significantly harder than the native GG and HPMC compacts. GDS matrices exhibited the fastest erosion and drug release in deionised water and phosphate buffer compared with the GG and HPMC. At pH 1.2, GDS exhibited greater swelling than erosion, and drug release was similar to GG and HPMC. This highlights the potential of GDS as a matrix for controlled release similar to HPMC and GG at pH 1.2 but with a more rapid release at pH 6.8. GDS may have wider application in reinforcing compacts with relatively low mechanical strength. PMID:26536530

  5. In vitro and in vivo evaluation of biodegradable embolic microspheres with tunable anticancer drug release.

    PubMed

    Weng, Lihui; Rostamzadeh, Parinaz; Nooryshokry, Navid; Le, Hung C; Golzarian, Jafar

    2013-06-01

    Natural polymer-derived materials have attracted increasing interest in the biomedical field. Polysaccharides have obvious advantages over other polymers employed for biomedical applications due to their exceptional biocompatibility and biodegradability. None of the spherical embolic agents used clinically is biodegradable. In the current study, microspheres prepared from chitosan and carboxymethyl cellulose (CMC) were investigated as a biodegradable embolic agent for arterial embolization applications. Aside from the enzymatic degradability of chitosan units, the cross-linking bonds in the matrix, Schiff bases, are susceptible to hydrolytic cleavage in aqueous conditions, which would overcome the possible shortage of enzymes inside the arteries. The size distribution, morphology, water retention capacity and degradability of the microspheres were found to be affected by the modification degree of CMC. An anticancer drug, doxorubicin, was successfully incorporated into these microspheres for local release and thus for killing cancerous cells. These microspheres demonstrated controllable degradation time, variable swelling and tunable drug release profiles. Co-culture with human umbilical vein endothelial cells revealed non-cytotoxic nature of these microspheres compared to monolayer control (P>0.95). In addition, a preliminary study on the in vivo degradation of the microspheres (100-300μm) was performed in a rabbit renal embolization model, which demonstrated that the microspheres were compatible with microcatheters for delivery, capable of occluding the arteries, and biodegradable inside arteries. These microspheres with biodegradability would be promising for embolization therapies. PMID:23419554

  6. Preparation of TiO2 nanotubes/mesoporous calcium silicate composites with controllable drug release.

    PubMed

    Xie, Chunling; Li, Ping; Liu, Yan; Luo, Fei; Xiao, Xiufeng

    2016-10-01

    Nanotube structures such as TiO2 nanotube (TNT) arrays produced by self-ordering electrochemical anodization have been extensively explored for drug delivery applications. In this study, we presented a new implantable drug delivery system that combined mesoporous calcium silicate coating with nanotube structures to achieve a controllable drug release of water soluble and antiphlogistic drug loxoprofen sodium. The results showed that the TiO2 nanotubes/mesoporous calcium silicate composites were successfully fabricated by a simple template method and the deposition of mesoporous calcium silicate increased with the soaking time. Moreover, the rate of deposition of biological mesoporous calcium silicate on amorphous TNTs was better than that on anatase TNTs. Further, zinc-incorporated mesoporous calcium silicate coating, produced by adding a certain concentration of zinc nitrate into the soaking system, displayed improved chemical stability. A significant improvement in the drug release characteristics with reduced burst release and sustained release was demonstrated. PMID:27287140

  7. [Examination of liquid crystalline gel systems containing chlorhexidine on the structure and the drug release].

    PubMed

    Farkas, E

    2001-10-01

    The aim of the thesis was to examine liquid crystalline gel systems as novel, locally applied drug delivery systems. For developing liquid crystalline vehicle, different ratio of Synperonic A7--water mixtures was prepared. Chlorhexidine, chlorhexidine acetate and chlorhexidine gluconate were used as model drugs. Liquid crystalline structure, drug release and drug release kinetic of the samples were studied at increasing surfactant concentration and the effect of the different drugs on the physicochemical properties of the samples and on the membrane transport was examined. For the analysis of the prepared liquid crystalline systems polarising microscopy, rheology test, differential scanning calorimetry, small-angle neutron scattering and transmission electron microscopy were carried out. The drug release and membrane transport experiments were performed by Franz type vertical diffusion cell and Sartorius Resorptionsmodell apparatus. According to our results liquid crystalline vehicles of lamellar and hexagonal structure formed by increasing the surfactant concentration. The drug release studies indicated, that the kinetic of the release strongly depend on the liquid crystalline structure, zero order release occurs from hexagonal structures and anomalous transport occurs from lamellar structures. The addition of chlorhexidine species to the systems modified the structure of the liquid crystalline system. As a results of liquid crystal-drug interaction the solubility of chlorhexidine base and its diffusion through lipophilic membranes increased in comparison with those of the chlorhexidine salts. PMID:11961906

  8. The Impact of Bubbles on Measurement of Drug Release from Echogenic Liposomes

    PubMed Central

    Kopechek, Jonathan A.; Haworth, Kevin J.; Radhakrishnan, Kirthi; Huang, Shaoling; Klegerman, Melvin E.; McPherson, David D.; Holland, Christy K.

    2013-01-01

    Echogenic liposomes (ELIP) encapsulate gas bubbles and drugs within lipid vesicles, but the mechanisms of ultrasound-mediated drug release from ELIP are not well understood. The effect of cavitation activity on drug release from ELIP was investigated in flowing solutions using two fluorescent molecules: a lipophilic drug (rosiglitazone) and a hydrophilic drug substitute (calcein). ELIP samples were exposed to pulsed Doppler ultrasound from a clinical diagnostic ultrasound scanner at pressures above and below the inertial and stable cavitation thresholds. Control samples were exposed to a surfactant, Triton X-100 (positive control), or to flow alone (negative control). Fluorescence techniques were used to detect release. Encapsulated microbubbles reduced the measured fluorescence intensity and this effect should be considered when assessing drug release from ELIP. The origin of this effect is not specific to ELIP. Release of rosiglitazone or calcein compared to the negative control was only observed with detergent treatment, but not with ultrasound exposure, despite the presence of stable and inertial cavitation activity. Release of rosiglitazone or calcein from ELIP exposed to diagnostic ultrasound was not observed, even in the presence of cavitation activity. Ultrasound-mediated drug delivery strategies with ELIP will thus rely on passage of the drug-loaded liposomes to target tissues. PMID:23357288

  9. A novel graphene nanodots inlaid porous gold electrode for electrochemically controlled drug release.

    PubMed

    Wang, Jianmei; Yang, Peng; Cao, Mengmei; Kong, Na; Yang, Wenrong; Sun, Shu; Meng, You; Liu, Jingquan

    2016-01-15

    A uniform graphene nanodots inlaid porous gold electrode was prepared via ion beam sputtering deposition (IBSD) and mild corrosion chemistry. HRTEM, SEM, AFM and XPS analyses revealed the successful fabrication of graphene nanodots inlaid porous gold electrode. The as-prepared porous electrode was used as π-orbital-rich drug loading platform to fabricate an electrochemically controlled drug release system with high performance. π-orbital-rich drugs with amino mioety, like doxorubicin (DOX) and tetracycline (TC), were loaded into the graphene nanodots inlaid porous gold electrode via non-covalent π-π stacking interaction. The amino groups in DOX and TC can be easily protonated at acidic medium to become positively-charged NH3(+), which allow these drug molecules to be desorbed from the porous electrode surface via electrostatic repulsion when positive potential is applied at the electrode. The drug loading and release experiment indicated that this graphene nanodots inlaid porous gold electrode can be used to conveniently and efficiently control the drug release electrochemically. Not only did our work provide a benign method to electrochemically controlled drug release via electrostatic repulsion process, it also enlighten the promising practical applications of micro electrode as a drug carrier for precisely and efficiently controlled drug release via embedding in the body. PMID:26592594

  10. pH-responsive amphiphilic hydrogel networks with IPN structure: a strategy for controlled drug release.

    PubMed

    Liu, Yu-Yang; Fan, Xiao-Dong; Wei, Bo-Rong; Si, Qing-Fa; Chen, Wei-Xing; Sun, Le

    2006-02-01

    A pH-responsive amphiphilic hydrogel with interpenetrating polymer networks (IPN) structure for controlled drug release was proposed. The IPN was constructed with hydrophilic poly(acrylic acid) (PAA) and hydrophobic poly(butyl acrylate) (PBA). Using drug N-acetyl-5-methoxytryptamine (melatonin, MEL) as a model molecule, the controlled drug release behaviors of the IPN were investigated. It is found that not only the release of MEL from the IPN can respond to change in pH, but also the presence of hydrophobic network can overcome disadvantageous burst effect of hydrophilic network. This may be a result of hydrophobic aggregation encapsulating MEL molecules. PMID:16321489

  11. Natural melanin: a potential pH-responsive drug release device.

    PubMed

    Araújo, Marco; Viveiros, Raquel; Correia, Tiago R; Correia, Ilídio J; Bonifácio, Vasco D B; Casimiro, Teresa; Aguiar-Ricardo, Ana

    2014-07-20

    This work proposes melanin as a new nanocarrier for pH-responsive drug release. Melanin is an abundant natural polymer that can be easily extracted from cuttlefish as nanoparticles with a suitable size range for drug delivery. However, despite its high potentiality, the application of this biopolymer in the pharmaceutical and biomedical fields is yet to be explored. Herein, melanin nanoparticles were impregnated with metronidazole, chosen as model antibiotic drug, using supercritical carbon dioxide. The drug release profile was investigated at acidic and physiologic pH, and the dominant mechanism was found to follow a non-Fickian transport. Drug release from melanin shows a strong pH dependency, which allied to its biocompatibility and lack of cytotoxicity envisages its potential application as nanocarrier in formulations for colon and intestine targeted drug delivery. PMID:24768404

  12. Therapeutic Efficacy of Combining PEGylated Liposomal Doxorubicin and Radiofrequency (RF) Ablation: Comparison between Slow-Drug-Releasing, Non-Thermosensitive and Fast-Drug-Releasing, Thermosensitive Nano-Liposomes

    PubMed Central

    Andriyanov, Alexander V.; Koren, Erez; Barenholz, Yechezkel

    2014-01-01

    Aims To determine how the accumulation of drug in mice bearing an extra-hepatic tumor and its therapeutic efficacy are affected by the type of PEGylated liposomal doxorubicin used, treatment modality, and rate of drug release from the liposomes, when combined with radiofrequency (RF) ablation. Materials and Methods Two nano-drugs, both long-circulating PEGylated doxorubicin liposomes, were formulated: (1) PEGylated doxorubicin in thermosensitive liposomes (PLDTS), having a burst-type fast drug release above the liposomes’ solid ordered to liquid disordered phase transition (at 42°C), and (2) non-thermosensitive PEGylated doxorubicin liposomes (PLDs), having a slow and continuous drug release. Both were administered intravenously at 8 mg/kg doxorubicin dose to tumor-bearing mice. Animals were divided into 6 groups: no treatment, PLD, RF, RF+PLD, PLDTS, and PLDTS+RF, for intra-tumor doxorubicin deposition at 1, 24, and 72 h post-injection (in total 41, mice), and 31 mice were used for randomized survival studies. Results Non-thermosensitive PLD combined with RF had the least tumor growth and the best end-point survival, better than PLDTS+RF (p<0.005) or all individual therapies (p<0.001). Although at 1 h post-treatment the greatest amount of intra-tumoral doxorubicin was seen following PLDTS+RF (p<0.05), by 24 and 72 h the greatest doxorubicin amount was seen for PLD+RF (p<0.05); in this group the tumor also has the longest exposure to doxorubicin. Conclusion Optimizing therapeutic efficacy of PLD requires a better understanding of the relationship between the effect of RF on tumor microenvironment and liposome drug release profile. If drug release is too fast, the benefit of changing the microenvironment by RF on tumor drug localization and therapeutic efficacy may be much smaller than for PLDs having slow and temperature-independent drug release. Thus the much longer circulation time of doxorubicin from PLD than from PLDTS may be beneficial in many therapeutic

  13. Controlled release of a hydrophilic drug from coaxially electrospun polycaprolactone nanofibers.

    PubMed

    Sultanova, Zahida; Kaleli, Gizem; Kabay, Gözde; Mutlu, Mehmet

    2016-05-30

    A recent approach for controlled release of drugs is the production of core-shell fibers via modified coaxial electrospinning where a shell solution which is not fully electrospinnable can be used. In this study, this technique was used for achieving the controlled release of a model hydrophilic drug (ampicillin) which is known to have a low compatibility with the polymer (polycaprolactone). A partially electrospinnable shell fluid (4% (w/v) polycaprolactone (PCL) solution) and a fully electrospinnable core fluid (10% (w/v) PCL, 2% (w/v) ampicillin solution) were used in order to create ampicillin-loaded PCL nanofibers covered by a PCL shield. Scanning electron microscopy and optical microscopy images proved that the membranes have core-shell structured nanofibers. Fourier transform infrared spectroscopy demonstrated that some compatibility might be present between ampicillin and PCL. Finally, drug release studies showed that the drug release kinetics of core-shell products is closer to zero-order kinetics while the drug release kinetics of single electrospinning of the core resulted with serious burst release. Together, these imply that the application area of modified coaxial electrospinning in controlled release could be expanded to polymers and drugs with low compatibility. PMID:27012983

  14. Tuning drug loading and release properties of diatom silica microparticles by surface modifications.

    PubMed

    Bariana, Manpreet; Aw, Moom Sinn; Kurkuri, Mahaveer; Losic, Dusan

    2013-02-25

    Diatomaceous earth (DE), or diatomite silica microparticles originated from fossilized diatoms are a potential substitute for its silica-based synthetic counterparts to address limitations in conventional drug delivery. This study presents the impact of engineered surface chemistry of DE microparticles on their drug loading and release properties. Surface modifications with four silanes, including 3-aminopropyltriethoxy silane (APTES), methoxy-poly-(ethylene-glycol)-silane (mPEG-silane), 7-octadecyltrichlorosilane (OTS), 3-(glycidyloxypropyl)trimethoxysilane (GPTMS) and two phosphonic acids, namely 2-carboxyethyl-phosphonic acid (2 CEPA) and 16-phosphono-hexadecanoic acid (16 PHA) were explored in order to tune drug loading and release characteristics of water insoluble (indomethacin) and water soluble drugs (gentamicin). Successful grafting of these functional groups with different interfacial properties was confirmed using X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR). Thermogravimetric analysis (TGA) was applied to determine the amount of loaded drugs and UV-spectrophotometry to analyse in vitro drug release from modified DE microparticles. Differences in drug release time (13-26 days) and loading capacity (14-24%) were observed depending on functional groups on the surface of DE microparticles. It was found that hydrophilic surfaces, due to the presence of polar carboxyl, amine or hydrolyzed epoxy group, favor extended release of indomethacin, while the hydrophobic DE surface modified by organic hydrocarbons gives a better sustained release profile for gentamicin. This work demonstrates that by changing surface functionalities on DE microparticles, it is possible to tune their drug loading and release characteristics for both hydrophobic and hydrophilic drugs and therefore achieve optimal drug delivery performance. PMID:23287775

  15. Surface Modifications of Titanium Implants by Multilayer Bioactive Coatings with Drug Delivery Potential: Antimicrobial, Biological, and Drug Release Studies

    NASA Astrophysics Data System (ADS)

    Ordikhani, Farideh; Zustiak, Silviya Petrova; Simchi, Abdolreza

    2016-04-01

    Recent strategies to locally deliver antimicrobial agents to combat implant-associated infections—one of the most common complications in orthopedic surgery—are gaining interest. However, achieving a controlled release profile over a desired time frame remains a challenge. In this study, we present an innovative multifactorial approach to combat infections which comprises a multilayer chitosan/bioactive glass/vancomycin nanocomposite coating with an osteoblastic potential and a drug delivery capacity. The bioactive drug-eluting coating was prepared on the surface of titanium foils by a multistep electrophoretic deposition technique. The adopted deposition strategy allowed for a high antibiotic loading of 1038.4 ± 40.2 µg/cm2. The nanocomposite coating exhibited a suppressed burst release with a prolonged sustained vancomycin release for up to 6 weeks. Importantly, the drug release profile was linear with respect to time, indicating a zero-order release kinetics. An in vitro bactericidal assay against Staphylococcus aureus confirmed that releasing the drug reduced the risk of bacterial infection. Excellent biocompatibility of the developed coating was also demonstrated by in vitro cell studies with a model MG-63 osteoblast cell line.

  16. Strontium-substituted, luminescent and mesoporous hydroxyapatite microspheres for sustained drug release.

    PubMed

    Jiang, Fei; Wang, De-Ping; Ye, Song; Zhao, Xin

    2014-02-01

    The multifunctional strontium (Sr)-substituted hydroxyapatite microsphere was prepared via hydrothermal method, in which the luminescent and controlled drug release functions can be realized. The structure and morphology of the as-prepared microspheres were studied by using XRD, FTIR, SEM, TEM, HR-TEM, BET method. The optical properties was investigated by using photoluminescence (PL) and XPS measurement. Then, the as-prepared multifunctional microspheres were performed as a drug delivery carrier using vancomycin as a model drug. The experimental results show that the composition, morphology, luminescent properties and drug storage/release behaviour were obviously influenced by the amount of Sr. The microspheres with Sr(2+)/(Ca(2+) + Sr(2+)) = 0.3 of Sr substitution showed the maximum specific surface area, best pore structure and strongest PL intensity. All the samples presented remarkable sustained drug release kinetics. In addition, the PL intensity of SrHA in the drug delivery system increased with the cumulative release time (amount) of vancomycin, which would make the drug release might be possibly tracked by the change of the luminescent intensity. Our study indicated a potential prospect that the fabricated multifunctional SrHA mesoporous microspheres might be applied in the field of bone regeneration and drug delivery. PMID:24402509

  17. Layered double hydroxides as effective carrier for anticancer drugs and tailoring of release rate through interlayer anions.

    PubMed

    Senapati, Sudipta; Thakur, Ravi; Verma, Shiv Prakash; Duggal, Shivali; Mishra, Durga Prasad; Das, Parimal; Shripathi, T; Kumar, Mohan; Rana, Dipak; Maiti, Pralay

    2016-02-28

    Hydrophobic anticancer drug, raloxifene hydrochloride (RH) is intercalated into a series of magnesium aluminum layered double hydroxides (LDHs) with various charge density anions through ion exchange technique for controlled drug delivery. The particle nature of the LDH in presence of drug is determined through electron microscopy and surface morphology. The release of drug from the RH intercalated LDHs was made very fast or sustained by altering the exchangeable anions followed by the modified Freundlich and parabolic diffusion models. The drug release rate is explained from the interactions between the drug and LDHs along with order-disorder structure of drug intercalated LDHs. Nitrate bound LDH exhibits greater interaction with drug and sustained drug delivery against the loosely interacted phosphate bound LDH-drug, which shows fast release. Cell viability through MTT assay suggests drug intercalated LDHs as better drug delivery vehicle for cancer cell line against poor bioavailability of the pure drug. In vivo study with mice indicates the differential tumor healing which becomes fast for greater drug release system but the body weight index clearly hints at damaged organ in the case of fast release system. Histopathological experiment confirms the damaged liver of the mice treated either with pure drug or phosphate bound LDH-drug, fast release system, vis-à-vis normal liver cell morphology for sluggish drug release system with steady healing rate of tumor. These observations clearly demonstrate that nitrate bound LDH nanoparticle is a potential drug delivery vehicle for anticancer drugs without any side effect. PMID:26774219

  18. The production of volvox spheres and their potential application in multi-drugs encapsulation and release.

    PubMed

    Teong, Benjamin; Chang, Shwu Jen; Chuang, Chin Wen; Kuo, Shyh Ming; Manousakas, Ioannis

    2013-12-01

    Volvox sphere is a bio-mimicking concept of an innovative biomaterial structure of a sphere that contains smaller microspheres which then encapsulate chemicals, drugs and/or cells. The volvox spheres were produced via a high-voltage electrostatic field system, using alginate as the primary material. Encapsulated materials tested in this study include staining dyes, nuclear fast red and trypan blue, and model drugs, bovine serum albumin (BSA) and cytochrome c (CytC). The external morphology of the volvox spheres was observed via electron microscopy whereas the internal structure of the volvox spheres was observed via an optical microscope with the aid of the staining dyes, since alginate is colorless and transparent. The diameter of the microspheres was about 200 to 300 μm, whereas the diameter of the volvox spheres was about 1500 μm. Volvox spheres were durable, retaining about 95% of their mass after 4 weeks. Factors affecting entrapment efficiency, such as temperature and concentration of the bivalent cross-linker, were compared followed by a 7-day in vitro release study. The encapsulation efficiency of CytC within the microspheres was higher at cold (~4°C) and warm (~50°C) temperatures whereas temperature has no obvious effect on the BSA encapsulation. High crosslinking concentration (25% w/v) of calcium chloride has resulted higher entrapment efficiency for BSA but not for CytC. Furthermore, volvox spheres showed a different release pattern of BSA and CytC when compared to microspheres encapsulating BSA and CytC. Despite the fact that the mechanisms behind remain unclear and further investigation is required, this study demonstrates the potential of the volvox spheres for drug delivery. PMID:24094197

  19. Potential application of functional porous TiO2 nanoparticles in light-controlled drug release and targeted drug delivery.

    PubMed

    Wang, Tianyi; Jiang, Haitao; Wan, Long; Zhao, Qinfu; Jiang, Tongying; Wang, Bing; Wang, Siling

    2015-02-01

    Novel multifunctional porous titanium dioxide (TiO2) nanoparticles modified with polyethylenimine (PEI) were developed to explore the feasibility of exploiting the photocatalytic property of titanium dioxide to achieve ultraviolet (UV) light triggered drug release. Additionally, in order to further realize targeting delivery, folic acid, which chemically conjugated to the surface of the functionalized multifunctional porous TiO2 nanoparticles through amide linkage with free amine groups of PEI, was used as a cancer-targeting agent to effectively promote cancer-cell-specific uptake through receptor-mediated endocytosis. And a typical poorly water-soluble anti-cancer drug, paclitaxel, was encapsulated in multifunctional porous TiO2 nanoparticles. The PEI on the surface of multifunctional porous TiO2 nanoparticles could effectively block the channel to prevent premature drug release, thus providing enough circulation time to target cancer cells. Following UV light radiation, PEI molecules on the surface were cut off by the free radicals (OH˙ and O2-) that TiO2 produced, and then the drug loaded in the carrier was released rapidly into the cytoplasm. Importantly, the amount of drug released from multifunctional porous TiO2 nanoparticles can be regulated by the UV-light radiation time to further control the anti-cancer effect. This multifunctional porous TiO2 nanoparticle exhibits a combination of stimuli-triggered drug release and cancer cell targeting. The authors believe that the present study will provide important information for the use of porous TiO2 nanomaterials in light-controlled drug release and targeted therapy. PMID:25462846

  20. Analytical and numerical study of diffusion-controlled drug release from composite spherical matrices.

    PubMed

    Hadjitheodorou, Amalia; Kalosakas, George

    2014-09-01

    We investigate, both analytically and numerically, diffusion-controlled drug release from composite spherical formulations consisting of an inner core and an outer shell of different drug diffusion coefficients. Theoretically derived analytical results are based on the exact solution of Fick's second law of diffusion for a composite sphere, while numerical data are obtained using Monte Carlo simulations. In both cases, and for the range of matrix parameter values considered in this work, fractional drug release profiles are described accurately by a stretched exponential function. The release kinetics obtained is quantified through a detailed investigation of the dependence of the two stretched exponential release parameters on the device characteristics, namely the geometrical radii of the inner core and outer shell and the corresponding drug diffusion coefficients. Similar behaviors are revealed by both the theoretical results and the numerical simulations, and approximate analytical expressions are presented for the dependencies. PMID:25063169

  1. Apparatus for studying in vitro drug release from medicated chewing gums.

    PubMed

    Kvist, C; Andersson, S B; Fors, S; Wennergren, B; Berglund, J

    1999-10-28

    An apparatus for in vitro drug release testing of medicated chewing gums has been developed and is described in detail. The effects on the drug release when varying critical instrumental settings such as the chewing stroke frequency, the distance between the chewing surfaces, the twisting movements of these surfaces and the temperature of the test medium have been thoroughly investigated. It has been shown that the drug release can be tuned to obtain suitable drug release profiles for a number of products: Nicorette((R)) and Nicotinell((R)) (active substance nicotine), Travvell((R)) (dimenhydrinate), V6((R)) (xylitol) and an experimental formulation containing meclizine. The main usage of the present apparatus should be within quality control but the present study has also shown that it may be employed within development pharmaceutics since useful in vivo/in vitro relationships may be obtained due to the versatile settings of the critical instrumental parameters. PMID:10518685

  2. Stimuli-free programmable drug release for combination chemo-therapy

    NASA Astrophysics Data System (ADS)

    Fan, Li; Jin, Boquan; Zhang, Silu; Song, Chaojun; Li, Quan

    2016-06-01

    Combinational chemotherapy capable of targeted delivery and programmable multi-drug release leads to enhanced drug efficacy, and is highly desired for cancer treatment. However, effective approaches for achieving both features in a single treatment are limited. In the present work, we demonstrated programmed delivery of both chemotherapeutic and immunotherapeutic agents with tumor cell targeting capability by using SiO2 based self-decomposable nanoparticulate systems. The programmable drug delivery is realized by manipulating drug loading configurations instead of relying on external stimuli. Both in vitro and in vivo results showed specific drug binding to FAT1-expressing colon cancer cells. The loaded dual drugs were demonstrated to be delivered in a sequential manner with specific time intervals between their peak releases, which maximize the synergistic effect of the chemotherapeutics. These features led to significantly enhanced drug efficacy and reduced system toxicity. The tumor weight decreased by 1/350, together with a moderate increase in rats' body weight, which were observed when adopting the dual drug loaded nanoparticles, as compared to those of the control groups. The present system provides a simple and feasible method for the design of targeting and combination chemotherapy with programmed drug release.Combinational chemotherapy capable of targeted delivery and programmable multi-drug release leads to enhanced drug efficacy, and is highly desired for cancer treatment. However, effective approaches for achieving both features in a single treatment are limited. In the present work, we demonstrated programmed delivery of both chemotherapeutic and immunotherapeutic agents with tumor cell targeting capability by using SiO2 based self-decomposable nanoparticulate systems. The programmable drug delivery is realized by manipulating drug loading configurations instead of relying on external stimuli. Both in vitro and in vivo results showed specific drug

  3. Osmotic Drug Delivery System as a Part of Modified Release Dosage Form

    PubMed Central

    Keraliya, Rajesh A.; Patel, Chirag; Patel, Pranav; Keraliya, Vipul; Soni, Tejal G.; Patel, Rajnikant C.; Patel, M. M.

    2012-01-01

    Conventional drug delivery systems are known to provide an immediate release of drug, in which one can not control the release of the drug and can not maintain effective concentration at the target site for longer time. Controlled drug delivery systems offer spatial control over the drug release. Osmotic pumps are most promising systems for controlled drug delivery. These systems are used for both oral administration and implantation. Osmotic pumps consist of an inner core containing drug and osmogens, coated with a semipermeable membrane. As the core absorbs water, it expands in volume, which pushes the drug solution out through the delivery ports. Osmotic pumps release drug at a rate that is independent of the pH and hydrodynamics of the dissolution medium. The historical development of osmotic systems includes development of the Rose-Nelson pump, the Higuchi-Leeper pumps, the Alzet and Osmet systems, the elementary osmotic pump, and the push-pull system. Recent advances include development of the controlled porosity osmotic pump, and systems based on asymmetric membranes. This paper highlights the principle of osmosis, materials used for fabrication of pumps, types of pumps, advantages, disadvantages, and marketed products of this system. PMID:22852100

  4. Tuning dual-drug release from composite scaffolds for bone regeneration.

    PubMed

    Paris, J L; Román, J; Manzano, M; Cabañas, M V; Vallet-Regí, M

    2015-01-01

    This work presents the tuning of drug-loaded scaffolds for bone regeneration as dual-drug delivery systems. Two therapeutic substances, zoledronic acid (anti-osteoporotic drug) and ibuprofen (anti-inflammatory drug) were successfully incorporated in a controlled manner into three dimensional designed porous scaffolds of apatite/agarose composite. A high-performance liquid chromatography method was optimized to separate and simultaneously quantify the two drugs released from the dual-drug codelivery system. The multifunctional porous scaffolds fabricated show a very rapid delivery of anti-inflammatory (interesting to reduce inflammation after implantation), whereas the anti-osteoporotic drug showed sustained release behaviour (important to promote bone regeneration). Since ibuprofen release was faster than desired, this drug was encapsulated in chitosan spheres which were then incorporated into the scaffolds, obtaining a release profile suitable for clinical application. The results obtained open the possibility to simultaneously incorporate two or more drugs to an osseous implant in a controlled way improving it for bone healing application. PMID:25814035

  5. Photoinduced drug release from thermosensitive AuNPs-liposome using a AuNPs-switch.

    PubMed

    An, Xueqin; Zhang, Fan; Zhu, Yinyan; Shen, Weiguo

    2010-10-14

    A thermosensitive liposome with embedded AuNPs in a bilayer was prepared using supercritical CO(2). The AuNPs-liposome can absorb a certain wavelength light, convert optical energy into heat, induce phase transition, and release drug. The results show that drug release from the liposome is due to the photothermic effects inducing phase transition of the liposome rather than destruction of the liposome structure. PMID:20820547

  6. Laser-activated nano-biomaterials for tissue repair and controlled drug release

    SciTech Connect

    Matteini, P; Ratto, F; Rossi, F; Pini, R

    2014-07-31

    We present recent achievements of minimally invasive welding of biological tissue and controlled drug release based on laser-activated nano-biomaterials. In particular, we consider new advancements in the biomedical application of near-IR absorbing gold nano-chromophores as an original solution for the photothermal repair of surgical incisions and as nanotriggers of controlled drug release from hybrid biopolymer scaffolds. (laser biophotonics)

  7. Effects of hydrophobic drug polyesteric core interactions on drug loading and release properties of poly(ethylene glycol) polyester poly(ethylene glycol) triblock core shell nanoparticles

    NASA Astrophysics Data System (ADS)

    Khoee, Sepideh; Hassanzadeh, Salman; Goliaie, Bahram

    2007-05-01

    BAB amphiphilic triblock copolymers consisting of poly(ethylene glycol) (B) (PEG) as the hydrophilic segment and different polyesters (A) as the hydrophobic block were prepared by a polycondensation reaction as efficient model core-shell nanoparticles to assay the effect of interactions between the hydrophobic drug and the polyesteric core in terms of drug loading content and release profile. PEG-poly(hexylene adipate)-PEG (PEG-PHA-PEG) and PEG-poly(butylene adipate)-PEG (PEG-PBA-PEG) to PEG-poly(ethylene adipate)-PEG (PEG-PEA-PEG) core-shell type nanoparticles entrapping quercetin (an anticarcinogenic, allergy inhibitor and antibacterial agent), were prepared by a nanoprecipitation method and characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM) and x-ray diffraction (XRD) techniques. It was found that the obtained nanoparticles showed a smooth surface and spherical shape with controllable sizes in the range of 64-74 nm, while drug loading varied from 7.24% to 19% depending on the copolymer composition and the preparation conditions. The in vitro release behaviour exhibited a sustained release and was affected by the polymer-drug interactions. UV studies revealed the presence of hydrogen bonding as the main existing interaction between quercetin and polyesters in the nanosphere cores.

  8. Effect of drug content and agglomerate size on tabletability and drug release characteristics of bromhexine hydrochloridetalc agglomerates prepared by crystallo-co-agglomeration.

    PubMed

    Jadhav, Namdeo; Pawar, Atmaram; Paradkar, Anant

    2010-03-01

    The objective of the investigation was to study the effect of bromhexine hydrochloride (BXH) content and agglomerate size on mechanical, compressional and drug release properties of agglomerates prepared by crystallo-co-agglomeration (CCA). Studies on optimized batches of agglomerates (BXT1 and BXT2) prepared by CCA have showed adequate sphericity and strength required for efficient tabletting. Trend of strength reduction with a decrease in the size of agglomerates was noted for both batches, irrespective of drug loading. However, an increase in mean yield pressure (14.189 to 19.481) with an increase in size was observed for BXT2 having BXH-talc (1:15.7). Surprisingly, improvement in tensile strength was demonstrated by compacts prepared from BXT2, due to high BXH load, whereas BXT1, having a low amount of BXH (BXH-talc, 1:24), showed low tensile strength. Consequently, increased tensile strength was reflected in extended drug release from BXT2 compacts (Higuchi model, R(2) = 0.9506 to 0.9981). Thus, it can be concluded that interparticulate bridges formed by BXH and agglomerate size affect their mechanical, compressional and drug release properties. PMID:20228039

  9. Effect of Polyethylene Glycol and Sodium Lauryl Sulphate on the Compaction Characteristics of Eudragit and Drug Release from its Matrix

    NASA Astrophysics Data System (ADS)

    Emeje, M. O.; Isimi, C. Y.; Kunle, O. O.; Ofoefule, S. I.

    A study on the compaction characteristics of Eudragit l-100 both in the presence and in the absence of two commonly used additives, polyethylene glycol 6000 (PEG 6000) and Sodium Lauryl Sulphate (SLS) was done. Eudragit granules, with and without the additives and drug were prepared separately by the wet granulation method and compacts were made at varying compression pressures. Compaction characteristics using Kawakita and Heckel analysis revealed a concentration dependent effect of the additives on the compressibility of Eudragit granules, with 2.5% PEG 6000 producing the largest effect and 5.0% PEG 6000, the least. Irrespective of the concentration of PEG 6000, the yield value increased, while SLS either had no effect or decreased the yield value of Eudragit granules. The highest yield value of 21.69 kN was produced by formulations containing 2.5% PEG 6000. While in some cases, the effect of the additive was slight, in others, it was drastic. The extent and nature of the effect depended on both the type and concentration of the additive used. SLS was found to increase the deformation of Eudragit more than PEG 6000. In vitro dissolution in simulated intestinal fluid as indicated by time for 70% drug release (t70%) shows that both additives modulated drug release, with 2.5 % SLS and 5% PEG 6000 enhancing drug release, while 5% SLS resulted in retarded but erratic drug release. The results of this study show that additives such as PEG 6000 and SLS affect the compaction characteristics of Eudragit l-100 and these were also found to affect the retardant behavior of Eudragit.

  10. Release of Water Soluble Drugs from Dynamically Swelling POLY(2-HYDROXYETHYL Methacrylate - CO - Methacrylic Acid) Hydrogels.

    NASA Astrophysics Data System (ADS)

    Kou, Jim Hwai-Cher

    In this study, ionizable copolymers of HEMA and methacrylic acid (MA) are investigated for their potential use in developing pH dependent oral delivery systems. Because of the MA units, these gels swell extensively at high pH. Since solute diffusion in the hydrophilic polymers depends highly on the water content of the matrix, it is anticipated that the release rate will be modulated by this pH induced swelling. From a practical point of view, the advantage of the present system is that one can minimize drug loss in the stomach and achieve a programmed release in intestine. This approach is expected to improve delivery of acid labile drugs or drugs that cause severe gastrointestinal side effects. This work mainly focuses on the basic understanding of the mechanism involved in drug release from the poly(HEMA -co- MA) gels, especially under dynamic swelling conditions. Equilibrium swelling is first characterized since water content is the major determinant of transport properties in these gels. Phenylpropanolamine (PPA) is chosen as the model drug for the release study and its diffusion characteristics in the gel matrix determined. The data obtained show that the PPA diffusivity follows the free volume theory of Yasuda, which explains the accelerating effect of swelling on drug release. A mathematical model based on a diffusion mechanism has been developed to describe PPA release from the swelling gels. Based on this model, several significant conclusions can be drawn. First, the release rate can be modulated by the aspect ratio of the cylindrical geometry, and this has a practical implication in dosage form design. Second, the release rate can be lowered quite considerably if the dimensional increase due to swelling is significant. Consequently, it is the balance between the drug diffusivity increase and the gel dimensional growth that determines the release rate from the swelling matrix. Third, quasi-steady release kinetics, which are characteristic of swelling

  11. Drug release characteristics from nanoclay hybrids and their dispersions in organic polymers.

    PubMed

    Ha, Jin Uk; Xanthos, Marino

    2011-07-29

    This study establishes and compares structure-property-processing relationships on three drug delivery systems containing an anionic active pharmaceutical ingredient (API) in the following excipient carriers: (a) an inorganic anionic nanoclay, (b) pH responsive acrylic polymers, and (c) combinations thereof. The effects of the excipients on the APIs dissolution rate were studied from their release profile in simulated body fluids (SBFs) with different pH. In the API-nanoclay system, calcination of the clay followed by its reconstitution in an API solution was successfully used to intercalate the API in its amorphous state in the clay. As a result, the API showed increased apparent solubility vs. its crystalline form with its release mechanism from the clay being predominantly diffusion controlled and depending on the pH of the SBFs. In melt mixed ternary polymer systems containing the above hybrids, as a result of an additional diffusional step due to presence of nanoplatelets, the API showed a more controlled release vs. polymer systems that contained only API. By comparison to the low pH SBF, the ternary system in the pH 7.4 SBF showed a reduced diffusion contribution due to the presence of clay platelets, the latter unaffected by the high pH value. Reasonable agreement was found with predictions from literature diffusion/erosion models. It is confirmed that hot melt mixing offers opportunities to produce systems with enhanced API apparent solubility. The presence of nanoclays can also increase the API's apparent solubility and affect its release in a controlled manner. PMID:21601624

  12. In Vitro Release Kinetics of Antituberculosis Drugs from Nanoparticles Assessed Using a Modified Dissolution Apparatus

    PubMed Central

    Gao, Yuan; Zuo, Jieyu; Bou-Chacra, Nadia; Pinto, Terezinha de Jesus Andreoli; Clas, Sophie-Dorothee; Walker, Roderick B.; Löbenberg, Raimar

    2013-01-01

    The aim of this study was to assess the in vitro release kinetics of antituberculosis drug-loaded nanoparticles (NPs) using a “modified” cylindrical apparatus fitted with a regenerated cellulose membrane attached to a standard dissolution apparatus (modifiedcylinder method). The model drugs that were used were rifampicin (RIF) and moxifloxacin hydrochloride (MX). Gelatin and polybutyl cyanoacrylate (PBCA) NPs were evaluated as the nanocarriers, respectively. The dissolution and release kinetics of the drugs from loaded NPs were studied in different media using the modified cylinder method and dialysis bag technique was used as the control technique. The results showed that use of the modified cylinder method resulted in different release profiles associated with unique release mechanisms for the nanocarrier systems investigated. The modified cylinder method also permitted discrimination between forced and normal in vitro release of the model drugs from gelatin NPs in the presence or absence of enzymatic degradation. The use of dialysis bag technique resulted in an inability to differentiate between the mechanisms of drug release from the NPs in these cases. This approach offers an effective tool to investigate in vitro release of RIF and MX from NPs, which further indicate that this technique can be used for performance testing of nanosized carrier systems. PMID:23936771

  13. Drug release control and system understanding of sucrose esters matrix tablets by artificial neural networks.

    PubMed

    Chansanroj, Krisanin; Petrović, Jelena; Ibrić, Svetlana; Betz, Gabriele

    2011-10-01

    Artificial neural networks (ANNs) were applied for system understanding and prediction of drug release properties from direct compacted matrix tablets using sucrose esters (SEs) as matrix-forming agents for controlled release of a highly water soluble drug, metoprolol tartrate. Complexity of the system was presented through the effects of SE concentration and tablet porosity at various hydrophilic-lipophilic balance (HLB) values of SEs ranging from 0 to 16. Both effects contributed to release behaviors especially in the system containing hydrophilic SEs where swelling phenomena occurred. A self-organizing map neural network (SOM) was applied for visualizing interrelation among the variables and multilayer perceptron neural networks (MLPs) were employed to generalize the system and predict the drug release properties based on HLB value and concentration of SEs and tablet properties, i.e., tablet porosity, volume and tensile strength. Accurate prediction was obtained after systematically optimizing network performance based on learning algorithm of MLP. Drug release was mainly attributed to the effects of SEs, tablet volume and tensile strength in multi-dimensional interrelation whereas tablet porosity gave a small impact. Ability of system generalization and accurate prediction of the drug release properties proves the validity of SOM and MLPs for the formulation modeling of direct compacted matrix tablets containing controlled release agents of different material properties. PMID:21878388

  14. Impact of cross-linker on alginate matrix integrity and drug release.

    PubMed

    Ching, A L; Liew, C V; Heng, P W S; Chan, L W

    2008-05-01

    Sodium alginate, a biopolymer, was employed in the formulation of matrix tablets. They cracked or laminated at acidic pH, compromising their dissolution performance. Improved mechanical strength and reduced barrier permeability of calcium alginate gel provided the rationale for cross-linking the alginate matrix to sustain drug release. Studies had suggested that the incorporation of soluble calcium salts in alginate matrix tablets could sustain drug release at near-neutral pH due to in situ cross-linking. However, results from the present study showed otherwise when gastrointestinal pH conditions were simulated. Significant reduction in drug release rate was only observed when an external calcium source was utilized at low concentration. High calcium ion concentrations caused matrix disintegration. In contrast, matrices pre-coated by calcium alginate could sustain drug release at pH 1.2 followed by pH 6.8 for over 12h. The presence of cross-linked barrier impeded matrix lamination and preserved matrix structure, contributing to at least three-fold reduction in drug release at pH 1.2. Zero order release as well as delayed burst release could be achieved by employing appropriate grade of alginate and cross-linking conditions. PMID:18272307

  15. NIR-driven Smart Theranostic Nanomedicine for On-demand Drug Release and Synergistic Antitumour Therapy

    NASA Astrophysics Data System (ADS)

    Zhao, Pengfei; Zheng, Mingbin; Luo, Zhenyu; Gong, Ping; Gao, Guanhui; Sheng, Zonghai; Zheng, Cuifang; Ma, Yifan; Cai, Lintao

    2015-09-01

    Smart nanoparticles (NPs) that respond to external and internal stimulations have been developing to achieve optimal drug release in tumour. However, applying these smart NPs to attain high antitumour performance is hampered by limited drug carriers and inefficient spatiotemporal control. Here we report a noninvasive NIR-driven, temperature-sensitive DI-TSL (DOX/ICG-loaded temperature sensitive liposomes) co-encapsulating doxorubicin (DOX) and indocyanine green (ICG). This theranostic system applies thermo-responsive lipid to controllably release drug, utilizes the fluorescence (FL) of DOX/ICG to real-time trace the distribution of NPs, and employs DOX/ICG to treat cancer by chemo/photothermal therapy. DI-TSL exhibits uniform size distribution, excellent FL/size stability, enhanced response to NIR-laser, and 3 times increased drug release through laser irradiation. After endocytosis by MCF-7 breast adenocarcinoma cells, DI-TSL in cellular endosomes can cause hyperthermia through laser irradiation, then endosomes are disrupted and DI-TSL ‘opens’ to release DOX simultaneously for increased cytotoxicity. Furthermore, DI-TSL shows laser-controlled release of DOX in tumour, enhanced ICG and DOX retention by 7 times and 4 times compared with free drugs. Thermo-sensitive DI-TSL manifests high efficiency to promote cell apoptosis, and completely eradicate tumour without side-effect. DI-TSL may provide a smart strategy to release drugs on demand for combinatorial cancer therapy.

  16. Photo-inducible Crosslinked Nanoassemblies for pH-Controlled Drug Release

    PubMed Central

    Dickerson, Matthew; Winquist, Nickolas; Bae, Younsoo

    2014-01-01

    Purpose To control drug release from block copolymer nanoassemblies by variation in the degree of photo-crosslinking and inclusion of acid sensitive linkers. Methods Poly(ethylene glycol)-poly(aspartate-hydrazide-cinnamate) (PEG-CNM) block copolymers were prepared and conjugated with a model drug, doxorubicin (DOX), through acid sensitive hydrazone linkers. The block copolymers formed photo-inducible, self-assembled nanoassemblies (piSNAs), which were used to produce photo-inducible crosslinked nanoassemblies (piCNAs) through UV crosslinking. The nanoassemblies were characterized to determine particle size, surface charge, pH- and crosslinking-dependent DOX release, in vitro cytotoxicity, and intracellular uptake as a function of photo-crosslinking degree. Results Nanoassemblies with varying photo-crosslinking degrees were successfully prepared while retaining particle size and surface charge. Photo-crosslinking caused no noticeable change in DOX release from the nanoassemblies at pH 7.4, but the DOX-loaded nanoassemblies modulated drug release as a function of crosslinking at pH 6.0. The nanoassemblies showed similar cytotoxicity regardless of crosslinking degrees, presumably due to the low cellular uptake and cell nucleus drug accumulation. Conclusion Photo-crosslinking is useful to control drug release from pH-sensitive block copolymer nanoassemblies as a function of crosslinking without altering the particle properties, and thus providing unique tools to investigate the pharmaceutical effects of drug release on cellular response. PMID:24254196

  17. 3D printing of tablets containing multiple drugs with defined release profiles.

    PubMed

    Khaled, Shaban A; Burley, Jonathan C; Alexander, Morgan R; Yang, Jing; Roberts, Clive J

    2015-10-30

    We have employed three-dimensional (3D) extrusion-based printing as a medicine manufacturing technique for the production of multi-active tablets with well-defined and separate controlled release profiles for three different drugs. This 'polypill' made by a 3D additive manufacture technique demonstrates that complex medication regimes can be combined in a single tablet and that it is viable to formulate and 'dial up' this single tablet for the particular needs of an individual. The tablets used to illustrate this concept incorporate an osmotic pump with the drug captopril and sustained release compartments with the drugs nifedipine and glipizide. This combination of medicines could potentially be used to treat diabetics suffering from hypertension. The room temperature extrusion process used to print the formulations used excipients commonly employed in the pharmaceutical industry. Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR) and X-ray powder diffraction (XRPD) were used to assess drug-excipient interaction. The printed formulations were evaluated for drug release using USP dissolution testing. We found that the captopril portion showed the intended zero order drug release of an osmotic pump and noted that the nifedipine and glipizide portions showed either first order release or Korsmeyer-Peppas release kinetics dependent upon the active/excipient ratio used. PMID:26235921

  18. NIR-driven Smart Theranostic Nanomedicine for On-demand Drug Release and Synergistic Antitumour Therapy

    PubMed Central

    Zhao, Pengfei; Zheng, Mingbin; Luo, Zhenyu; Gong, Ping; Gao, Guanhui; Sheng, Zonghai; Zheng, Cuifang; Ma, Yifan; Cai, Lintao

    2015-01-01

    Smart nanoparticles (NPs) that respond to external and internal stimulations have been developing to achieve optimal drug release in tumour. However, applying these smart NPs to attain high antitumour performance is hampered by limited drug carriers and inefficient spatiotemporal control. Here we report a noninvasive NIR-driven, temperature-sensitive DI-TSL (DOX/ICG-loaded temperature sensitive liposomes) co-encapsulating doxorubicin (DOX) and indocyanine green (ICG). This theranostic system applies thermo-responsive lipid to controllably release drug, utilizes the fluorescence (FL) of DOX/ICG to real-time trace the distribution of NPs, and employs DOX/ICG to treat cancer by chemo/photothermal therapy. DI-TSL exhibits uniform size distribution, excellent FL/size stability, enhanced response to NIR-laser, and 3 times increased drug release through laser irradiation. After endocytosis by MCF-7 breast adenocarcinoma cells, DI-TSL in cellular endosomes can cause hyperthermia through laser irradiation, then endosomes are disrupted and DI-TSL ‘opens’ to release DOX simultaneously for increased cytotoxicity. Furthermore, DI-TSL shows laser-controlled release of DOX in tumour, enhanced ICG and DOX retention by 7 times and 4 times compared with free drugs. Thermo-sensitive DI-TSL manifests high efficiency to promote cell apoptosis, and completely eradicate tumour without side-effect. DI-TSL may provide a smart strategy to release drugs on demand for combinatorial cancer therapy. PMID:26400780

  19. Microfluidic Synthesis of Microfibers for Magnetic-Responsive Controlled Drug Release and Cell Culture

    PubMed Central

    Lin, Yung-Sheng; Huang, Keng-Shiang; Yang, Chih-Hui; Wang, Chih-Yu; Yang, Yuh-Shyong; Hsu, Hsiang-Chen; Liao, Yu-Ju; Tsai, Chia-Wen

    2012-01-01

    This study demonstrated the fabrication of alginate microfibers using a modular microfluidic system for magnetic-responsive controlled drug release and cell culture. A novel two-dimensional fluid-focusing technique with multi-inlets and junctions was used to spatiotemporally control the continuous laminar flow of alginate solutions. The diameter of the manufactured microfibers, which ranged from 211 µm to 364 µm, could be well controlled by changing the flow rate of the continuous phase. While the model drug, diclofenac, was encapsulated into microfibers, the drug release profile exhibited the characteristic of a proper and steady release. Furthermore, the diclofenac release kinetics from the magnetic iron oxide-loaded microfibers could be controlled externally, allowing for a rapid drug release by applying a magnetic force. In addition, the successful culture of glioblastoma multiforme cells in the microfibers demonstrated a good structural integrity and environment to grow cells that could be applied in drug screening for targeting cancer cells. The proposed microfluidic system has the advantages of ease of fabrication, simplicity, and a fast and low-cost process that is capable of generating functional microfibers with the potential for biomedical applications, such as drug controlled release and cell culture. PMID:22470443

  20. Inorganically modified diatomite as a potential prolonged-release drug carrier.

    PubMed

    Janićijević, Jelena; Krajišnik, Danina; Calija, Bojan; Dobričić, Vladimir; Daković, Aleksandra; Krstić, Jugoslav; Marković, Marija; Milić, Jela

    2014-09-01

    Inorganic modification of diatomite was performed with the precipitation product of partially neutralized aluminum sulfate solution at three different mass ratios. The starting and the modified diatomites were characterized by SEM-EDS, FTIR, thermal analysis and zeta potential measurements and evaluated for drug loading capacity in adsorption batch experiments using diclofenac sodium (DS) as a model drug. In vitro drug release studies were performed in phosphate buffer pH6.8 from comprimates containing: the drug adsorbed onto the selected modified diatomite sample (DAMD), physical mixture of the drug with the selected modified diatomite sample (PMDMD) and physical mixture of the drug with the starting diatomite (PMDD). In vivo acute toxicity testing of the modified diatomite samples was performed on mice. High adsorbent loading of the selected modified diatomite sample (~250mg/g in 2h) enabled the preparation of comprimates containing adsorbed DS in the amount near to its therapeutic dose. Drug release studies demonstrated prolonged release of DS over a period of 8h from both DAMD comprimates (18% after 8h) and PMDMD comprimates (45% after 8h). The release kinetics for DAMD and PMDMD comprimates fitted well with Korsmeyer-Peppas and Bhaskar models, indicating that the release mechanism was a combination of non-Fickian diffusion and ion exchange process. PMID:25063135

  1. Intelligent Janus nanoparticles for intracellular real-time monitoring of dual drug release.

    PubMed

    Cao, Han; Yang, Yuhong; Chen, Xin; Shao, Zhengzhong

    2016-03-28

    Stimuli-responsive nanomaterials have been receiving much attention as drug delivery carriers, however understanding of multi-drug release from the carriers for efficient therapeutics is highly challenging. Here, we report a novel nanosystem, Janus particle Dox-CMR-MS/Au-6MP (Dox: doxorubicin, CMR: 7-hydroxycoumarin-3-carboxylate, MS: mesoporous silica, Au: gold, 6MP: 6-mercaptopurine) with opposing MS and Au faces, which can monitor intracellular dual-drug (Dox and 6MP) controlled release in real time based on fluorescence resonance energy transfer (FRET) and surface-enhanced Raman scattering (SERS). The FRET acceptor Dox is attached to CMR (as a FRET donor) conjugated MS with a pH-responsive linker hydrazone, and 6MP is conjugated to the Au surface through the gold-thiol interaction. As the Janus nanoparticle enters into tumor cells, the breakage of the hydrazone bond in an acidic environment and the substitution of glutathione (GSH) overexpressed in cancer cells give rise to the release of Dox and 6MP, respectively. Thus, the change of the CMR fluorescence signal and the SERS decrease of 6MP can be used to monitor the dual-drug release within living cells in real time. In addition, this work demonstrates the enhanced anticancer effect of the designed dual-drug loaded nanosystem. Therefore, the current study may provide new perspectives for the real-time study of intelligent multi-drug delivery and release, as well as cellular responses to drug treatment. PMID:26952741

  2. Multilayer Coating of Tetrandrine-loaded PLGA nanoparticles: Effect of surface charges on cellular uptake rate and drug release profile.

    PubMed

    Meng, Rui; Li, Ke; Chen, Zhe; Shi, Chen

    2016-02-01

    The effect of surface charges on the cellular uptake rate and drug release profile of tetrandrine-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (TPNs) was studied. Stabilizer-free nanoprecipitation method was used in this study for the synthesis of TPNs. A typical layer-by-layer approach was applied for multi-coating particles' surface with use of poly(styrene sulfonate) sodium salt (PSS) as anionic layer and poly(allylamine hydrochloride) (PAH) as cationic layer. The modified TPNs were characterized by different physicochemical techniques such as Zeta sizer, scanning electron microscopy and transmission electron microscopy. The drug loading efficiency, release profile and cellular uptake rate were evaluated by high performance liquid chromatography and confocal laser scanning microscopy, respectively. The resultant PSS/PAH/PSS/PAH/TPNs (4 layers) exhibited spherical-shaped morphology with the average size of 160.3±5.165 nm and zeta potential of-57.8 mV. The encapsulation efficiency and drug loading efficiency were 57.88% and 1.73%, respectively. Multi-layer coating of polymeric materials with different charges on particles' surface could dramatically influence the drug release profile of TPNs (4 layers vs. 3 layers). In addition, variable layers of surface coating could also greatly affect the cellular uptake rate of TPNs in A549 cells within 8 h. Overall, by coating particles' surface with those different charged polymers, precise control of drug release as well as cellular uptake rate can be achieved simultaneously. Thus, this approach provides a new strategy for controllable drug delivery. PMID:26838734

  3. Comparison in vitro felodipine release rate from the original versus generic product with controlled release of the drug.

    PubMed

    Vetchy, David; Vetcha, Martina; Rabiskova, Miloslava; Gryczova, Eva; Bartosikova, Lenka

    2007-01-01

    After patent protection of original brand is over, there are a lot of generic products occurring on the pharmaceutical market. It may be the way to reduce the price, but on the other hand, one should expect the same quality and almost identity with original brand, because the development of generic drugs is based on pharmacological properties of the original brand. The aim of this study was to compare the similarity of two products with controlled release of felodipine--generic product Presid and original brand Plendil--which are commercially available in Czech Republic, based on in vitro dissolution testing. The dissolution test in three dissolution media of increasing pH (1.2, 4.5, and 6.5) for the simulation of physiological pH within the gastrointestinal tract confirmed controlled release of felodipine from the original product Plendil ER 5 mg and Plendil ER 10 mg during the period of 24 hours. The release of felodipine from generic products Presid 5 mg and Presid 10 mg was not controlled for 24 hours as it is indicated in the information leaflet. In the generic products, felodipine release was controlled just for 12 or 18 hours and in this respect did not show similarity with the original brand. Since patients take the drug just once a day in the morning, the controlled release of felodipine, which lasts only 12 to 18 hours, can cause insufficient blood pressure control especially in the most critical morning hours and higher cardiovascular risk. PMID:17485960

  4. Injectable polyanhydride granules provide controlled release of water-soluble drugs with a reduced initial burst.

    PubMed

    Tabata, Y; Domb, A; Langer, R

    1994-01-01

    A method for preparing polyanhydride granules of an injectable size was developed. The resulting granules permitted a nearly constant release of low-molecular-weight, water-soluble drugs without an initial burst. The polyanhydrides used were poly(fatty acid dimer), poly(sebacic acid), and their copolymers. The dyes acid orange 63 and p-nitroaniline were used as model compounds for drugs. Polymer degradation and drug release for disks and variously sized granules of copolymers containing drugs, prepared by a water-in-oil (W/O) emulsion method, were compared with those for devices prepared by the usual compression method. In the W/O emulsion method, a mixture of aqueous drug solution and polymer-chloroform solution was emulsified by probe sonication to prepare a very fine W/O emulsion. The powder obtained by freeze-drying of the W/O emulsion was pressed into circular disks. In the compression method, the drug was mechanically mixed with the polymer, and the mixture was compressed into circular disks. The resulting disks were ground to prepare granules of different sizes. The granules encapsulated more than 95% of the drug, irrespective of the preparation method. Both methods were effective in preparing polymer disks capable of controlled drug release without any initial burst. However, as the granule size decreased to an injectable size (diameter, < 150 microns), a large difference in the drug release profile was observed between the two preparation methods. The injectable granules obtained by the W/O emulsion method showed nearly constant drug release without any large initial burst, in contrast to those prepared by the compression method, irrespective of the drug type.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8138910

  5. Evaluation of drug delivery profiles in geometric three-layered tablets with various mechanical properties, in vitro-in vivo drug release, and Raman imaging.

    PubMed

    Choi, Du Hyung; Kim, Ki Hyun; Park, Jun Sang; Jeong, Seong Hoon; Park, Kinam

    2013-12-28

    Even though various multi-layered tablets have been developed for sustained release formulations, evaluations of mechanical properties during dissolution with drug release and imaging in the tablets have been limited. A novel geometric system consisting of an inner immediate release layer and two extended release barrier layers with swellable hydrophilic polymers was suggested as a once-a-day formulation. To evaluate drug release mechanisms with geometric properties, various mechanical characteristics during swelling were investigated to comprehend the relationship among in vitro drug release, human pharmacokinetics, and geometric characteristics. Imaging of drug movement was also studied in real-time using Raman spectroscopy. Drug delivery in the tablets might be divided into three processes through the geometric properties. When exposed to aqueous environments, the drug in the mid-layer was released until wrapped by the swollen barrier layers. Then, the drug in the mid-layer was mainly delivered to the barrier layers and a small amount of the drug was delivered to the contact region of the swollen barrier layers. Finally, the delivered drug to the barrier layers was consistently released out in response to the characteristics of the polymer of the barrier layers. Using Raman spectroscopy, these processes were confirmed in real-time analysis. Moreover, in vitro drug release profiles and human pharmacokinetics showed consistent results suggesting that drug release might be dependent on the various geometric properties and be modified consistently during the formulation development. PMID:24035977

  6. Evaluating the effects of crystallinity in new biocompatible polyester nanocarriers on drug release behavior

    PubMed Central

    Karavelidis, Vassilios; Karavas, Evangelos; Giliopoulos, Dimitrios; Papadimitriou, Sofia; Bikiaris, Dimitrios

    2011-01-01

    Four new polyesters based on 1,3-propanediol and different aliphatic dicarboxylic acids were used to prepare ropinirole HCl-loaded nanoparticles. The novelty of this study lies in the use of polyesters with similar melting points but different degrees of crystallinity, varying from 29.8% to 67.5%, as drug nanocarriers. Based on their toxicity to human umbilical vein endothelial cells, these aliphatic polyesters were found to have cytotoxicity similar to that of polylactic acid and so may be considered as prominent drug nanocarriers. Drug encapsulation in polyesters was performed via an emulsification/solvent evaporation method. The mean particle size of drug-loaded nanoparticles was 164–228 nm, and the drug loading content was 16%–23%. Wide angle X-ray diffraction patterns showed that ropinirole HCl existed in an amorphous state within the nanoparticle polymer matrices. Drug release diagrams revealed a burst effect for ropinirole HCl in the first 6 hours, probably due to release of drug located on the nanoparticle surface, followed by slower release. The degree of crystallinity of the host polymer matrix seemed to be an important parameter, because higher drug release rates were observed in polyesters with a low degree of crystallinity. PMID:22162659

  7. Hybrid lipid-capped mesoporous silica for stimuli-responsive drug release and overcoming multidrug resistance.

    PubMed

    Han, Ning; Zhao, Qinfu; Wan, Long; Wang, Ying; Gao, Yikun; Wang, Pu; Wang, Zhanyou; Zhang, Jinghai; Jiang, Tongying; Wang, Siling

    2015-02-11

    Multidrug resistance (MDR) is known to be a great obstruction to successful chemotherapy, and considerable efforts have been devoted to reverse MDR including designing various functional drug delivery systems. In this study, hybrid lipid-capped mesoporous silica nanoparticles (LTMSNs), aimed toward achieving stimuli-responsive drug release to circumvent MDR, were specially designated for drug delivery. After modifying MSNs with hydrophobic chains through disulfide bond on the surface, lipid molecules composing polymer d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) with molar ratio of 5:1 were subsequently added to self-assemble into a surrounded lipid layer via hydrophobic interaction acting as smart valves to block the pore channels of carrier. The obtained LTMSNs had a narrow size distribution of ca. 190 nm and can be stably dispersed in body fluids, which may ensure a long circulating time and ideal enhanced permeability and retention effect. Doxorubicin (DOX) was chosen as a model drug to be encapsulated into LTMSNs. Results showed that this hybrid lipid-capped mesoporous silica drug delivery system can achieve redox and pH-responsive release of DOX, thereby avoiding the premature leakage of drug before reaching the specific site and releasing DOX within the cancerous cells. Owing to the presence of TPGS-containing lipid layer, LTMSNs-DOX exhibited higher uptake efficiency, cytotoxicity, and increased intracellular accumulation in resistant MCF-7/Adr cells compared with DOX solution, proving to be a promising vehicle to realize intracellular drug release and inhibit drug efflux. PMID:25584634

  8. Polypyrrole nanoparticles for tunable, pH-sensitive and sustained drug release

    NASA Astrophysics Data System (ADS)

    Samanta, Devleena; Meiser, Jana L.; Zare, Richard N.

    2015-05-01

    We report the development of a generalized pH-sensitive drug delivery system that can release any charged drug preferentially at the pH range of interest. Our system is based on polypyrrole nanoparticles (PPy NPs), synthesized via a simple one-step microemulsion technique. These nanoparticles are highly monodisperse, stable in solution over the period of a month, and have good drug loading capacity (~15 wt%). We show that PPy NPs can be tuned to release drugs at both acidic and basic pH by varying the pH, the charge of the drug, as well as by adding small amounts of charged amphiphiles. Moreover, these NPs may be delivered locally by immobilizing them in a hydrogel. Our studies show encapsulation within a calcium alginate hydrogel results in sustained release of the incorporated drug for more than 21 days. Such a nanoparticle-hydrogel composite drug delivery system is promising for treatment of long-lasting conditions such as cancer and chronic pain which require controlled, localized, and sustained drug release.

  9. Design Project on Controlled-Release Drug Delivery Devices: Implementation, Management, and Learning Experiences

    ERIC Educational Resources Information Center

    Xu, Qingxing; Liang, Youyun; Tong, Yen Wah; Wang, Chi-Hwa

    2010-01-01

    A design project that focuses on the subject of controlled-release drug delivery devices is presented for use in an undergraduate course on mass transfer. The purpose of the project is to introduce students to the various technologies used in the fabrication of drug delivery systems and provide a practical design exercise for understanding the…

  10. Biodegradable poly(vinyl alcohol)/polyoxalate electrospun nanofibers for hydrogen peroxide-triggered drug release.

    PubMed

    Phromviyo, Nutthakritta; Lert-Itthiporn, Aurachat; Swatsitang, Ekaphan; Chompoosor, Apiwat

    2015-01-01

    Release of drugs in a controlled and sustainable manner is of great interest for treating some inflammatory diseases, drug delivery, and cosmetics. In this work, we demonstrated the control release of a drug from composite nanofibers mediated by hydrogen peroxide. Composite nanofibers of polyvinyl alcohol (PVA)/polyoxalate (PVA/POX NFs) blended at various weight ratios were successfully prepared by electrospinning. Rhodamine B (RB) was used as a model of drug and was initially loaded into the POX portion. The morphology of NFs was characterized using scanning electron microscopy (SEM). The functional groups presented in the NFs were characterized using IR spectroscopy. In vitro release behavior and cell toxicity of nanofibers were also investigated using the MTT assay. The results indicated that POX content had a significant effect on the size and release profiles of nanofibers. Microstructure analysis revealed that sizes of PVA/POX NFs increased with increasing POX content, ranging from 214 to 422 nm. Release profiles of RB at 37 °C were non-linear and showed different release mechanisms. The mechanism of drug release depended on the chemical composition of the NFs. RB release from the NFs with highest POX content was caused by the degradation of the nanofiber matrix, whereas the RB release in lower POX content NFs was caused by diffusion. The NFs with POX showed a loss of structural integrity in the presence of hydrogen peroxide as seen using SEM. The MTT assay showed that composite nanofibers had minimal cytotoxicity. We anticipate that nanofibrous PVA/POX can potentially be used to target numerous inflammatory diseases that overproduce hydrogen peroxide and may become a potential candidate for use as a local drug delivery vehicle. PMID:26147088

  11. Externally controlled drug release using a gold nanorod contained composite membrane.

    PubMed

    Kim, Kibeom; Jo, Min-Chul; Jeong, Sundo; Palanikumar, L; Rotello, Vincent M; Ryu, Ja-Hyoung; Park, Myoung-Hwan

    2016-06-01

    Versatile drug delivery devices using nanoporous membranes consisting of gold nanorods and dendrimers have been demonstrated to provide light-triggered on-demand pulsatile release from a reservoir containing highly enriched therapeutics for a real patient's needs. The drug release rate is directly correlated with the temperature increase and irradiated energy of a near-IR laser in both static and fluidic devices. This biocompatible platform for on-demand control was further confirmed by in vitro experiments. Interestingly, different responses to stimuli were obtained from each drug in the absence and presence of NIR light, indicating the versatile potential of our on-demand drug delivery system in less-invasive therapies requiring multi-drug delivery strategies. The enhanced delivery system will improve therapeutic efficacy and reduce side effects through regulation of plasma drug profiles. PMID:27240476

  12. Gellan gum microspheres crosslinked with trivalent ion: effect of polymer and crosslinker concentrations on drug release and mucoadhesive properties.

    PubMed

    Boni, Fernanda Isadora; Prezotti, Fabíola Garavello; Cury, Beatriz Stringhetti Ferreira

    2016-08-01

    Gellan gum microspheres were obtained by ionotropic gelation technique, using the trivalent ion Al(3+). The percentage of entrapment efficiency ranged from 48.76 to 87.52% and 2(2) randomized full factorial design demonstrated that both the increase of polymer concentration and the decrease of crosslinker concentration presented a positive effect in the amount of encapsulated drug. Microspheres size and circularity ranged from 700.17 to 938.32 μm and from 0.641 to 0.796 μm, respectively. The increase of polymer concentration (1-2%) and crosslinker concentration (3-5%) led to the enlargement of particle size and circularity. However, the association of increased crosslinker concentration and reduced polymer content made the particles more irregular. In vitro and ex vivo tests evidenced the high mucoadhesiveness of microspheres. The high liquid uptake ability of the microspheres was demonstrated and the pH variation did not affect this parameter. Drug release was pH dependent, with low release rates in acid pH (42.40% and 44.93%) and a burst effect in phosphate buffer pH (7.4). The Weibull model had the best correlation with the drug release data, demonstrating that the release process was driven by a complex mechanism involving the erosion and swelling of the matrix or by non-Fickian diffusion. PMID:26616390

  13. Optical suppression of drug-evoked phasic dopamine release

    PubMed Central

    McCutcheon, James E.; Cone, Jackson J.; Sinon, Christopher G.; Fortin, Samantha M.; Kantak, Pranish A.; Witten, Ilana B.; Deisseroth, Karl; Stuber, Garret D.; Roitman, Mitchell F.

    2014-01-01

    Brief fluctuations in dopamine concentration (dopamine transients) play a key role in behavior towards rewards, including drugs of abuse. Drug-evoked dopamine transients may result from actions at both dopamine cell bodies and dopamine terminals. Inhibitory opsins can be targeted to dopamine neurons permitting their firing activity to be suppressed. However, as dopamine transients can become uncoupled from firing, it is unknown whether optogenetic hyperpolarization at the level of the soma is able to suppress dopamine transients. Here, we used in vivo fast-scan cyclic voltammetry to record transients evoked by cocaine and raclopride in nucleus accumbens (NAc) of urethane-anesthetized rats. We targeted halorhodopsin (NpHR) specifically to dopamine cells by injecting Cre-inducible virus into ventral tegmental area (VTA) of transgenic rats that expressed Cre recombinase under control of the tyrosine hydroxylase promoter (TH-Cre+ rats). Consistent with previous work, co-administration of cocaine and raclopride led to the generation of dopamine transients in NAc shell. Illumination of VTA with laser strongly suppressed the frequency of transients in NpHR-expressing rats, but not in control rats. Laser did not have any effect on amplitude of transients. Thus, optogenetics can effectively reduce the occurrence of drug-evoked transients and is therefore a suitable approach for studying the functional role of such transients in drug-associated behavior. PMID:25278845

  14. PLGA-based microparticles loaded with bacterial-synthesized prodigiosin for anticancer drug release: Effects of particle size on drug release kinetics and cell viability.

    PubMed

    Obayemi, J D; Danyuo, Y; Dozie-Nwachukwu, S; Odusanya, O S; Anuku, N; Malatesta, K; Yu, W; Uhrich, K E; Soboyejo, W O

    2016-09-01

    This paper presents the synthesis and physicochemical characterization of biodegradable poly (d,l-lactide-co-glycolide) (PLGA)-based microparticles that are loaded with bacterial-synthesized prodigiosin drug obtained from Serratia marcescens subsp. Marcescens bacteria for controlled anticancer drug delivery. The micron-sized particles were loaded with anticancer drugs [prodigiosin (PG) and paclitaxel (PTX) control] using a single-emulsion solvent evaporation technique. The encapsulation was done in the presence of PLGA (as a polymer matrix) and poly-(vinyl alcohol) (PVA) (as an emulsifier). The effects of processing conditions (on the particle size and morphology) are investigated along with the drug release kinetics and drug-loaded microparticle degradation kinetics. The localization and apoptosis induction by prodigiosin in breast cancer cells is also elucidated along with the reduction in cell viability due to prodigiosin release. The implication of this study is for the potential application of prodigiosin PLGA-loaded microparticles for controlled delivery of cancer drug and treatment to prevent the regrowth or locoregional recurrence, following surgical resection of triple negative breast tumor. PMID:27207038

  15. Externally controlled drug release using a gold nanorod contained composite membrane

    NASA Astrophysics Data System (ADS)

    Kim, Kibeom; Jo, Min-Chul; Jeong, Sundo; Palanikumar, L.; Rotello, Vincent M.; Ryu, Ja-Hyoung; Park, Myoung-Hwan

    2016-06-01

    Versatile drug delivery devices using nanoporous membranes consisting of gold nanorods and dendrimers have been demonstrated to provide light-triggered on-demand pulsatile release from a reservoir containing highly enriched therapeutics for a real patient's needs. The drug release rate is directly correlated with the temperature increase and irradiated energy of a near-IR laser in both static and fluidic devices. This biocompatible platform for on-demand control was further confirmed by in vitro experiments. Interestingly, different responses to stimuli were obtained from each drug in the absence and presence of NIR light, indicating the versatile potential of our on-demand drug delivery system in less-invasive therapies requiring multi-drug delivery strategies. The enhanced delivery system will improve therapeutic efficacy and reduce side effects through regulation of plasma drug profiles.Versatile drug delivery devices using nanoporous membranes consisting of gold nanorods and dendrimers have been demonstrated to provide light-triggered on-demand pulsatile release from a reservoir containing highly enriched therapeutics for a real patient's needs. The drug release rate is directly correlated with the temperature increase and irradiated energy of a near-IR laser in both static and fluidic devices. This biocompatible platform for on-demand control was further confirmed by in vitro experiments. Interestingly, different responses to stimuli were obtained from each drug in the absence and presence of NIR light, indicating the versatile potential of our on-demand drug delivery system in less-invasive therapies requiring multi-drug delivery strategies. The enhanced delivery system will improve therapeutic efficacy and reduce side effects through regulation of plasma drug profiles. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr00362a

  16. Chain-Shattering Polymeric Therapeutics with On-Demand Drug-Release Capability

    PubMed Central

    Zhang, Yanfeng; Yin, Qian; Yin, Lichen; Ma, Liang; Tang, Li

    2013-01-01

    Design of smart polymeric therapeutics We designed and synthesized trigger-responsive chain-shattering polymeric therapeutics (CSPTs) via condensation polymerization of a UV-or hydrogen peroxide-responsive domain and a bisfunctional drug as co-monomers. CSPTs have precisely controlled molecular composition and unique chain-shattering type of drug release mechanism. Drug release kinetics can be precisely controlled by means of the trigger treatment. Chemotherapeutic-containing CSPTs showed trigger-responsive in vitro and in vivo antitumor efficacy. PMID:23650111

  17. Thermosensitive PNIPAM-b-HTPB block copolymer micelles: molecular architectures and camptothecin drug release.

    PubMed

    Luo, Yan-Ling; Yang, Xiao-Li; Xu, Feng; Chen, Ya-Shao; Zhang, Bin

    2014-02-01

    Two kinds of thermo-sensitive poly(N-isoproplacrylamide) (PNIPAM) block copolymers, AB4 four-armed star multiblock and linear triblock copolymers, were synthesized by ATRP with hydroxyl-terminated polybutadiene (HTPB) as central blocks, and characterization was performed by (1)H NMR, FT-IR and SEC. The multiblock copolymers could spontaneously assemble into more regular spherical core-shell nanoscale micelles than the linear triblock copolymer. The physicochemical properties were detected by a surface tension technique, nano particle analyzer, TEM, DLS and UV-vis measurements. The multiblock copolymer micelles had lower critical micelle concentration than the linear counterpart, TEM size from 100 to 120 nm and the hydrodynamic diameters below 150 nm. The micelles exhibited thermo-dependent size change, with low critical solution temperature about 33-35 °C. The characteristic parameters were affected by the composition ratios, length of PNIPAM blocks and molecular architectures. The camptothecin release demonstrated that the drug release was thermo-responsive, accompanied by the temperature-induced structural changes of the micelles. MTT assays were performed to evaluate the biocompatibility or cytotoxicity of the prepared copolymer micelles. PMID:24184534

  18. Controlled Release of Simvastatin from Biomimetic β-TCP Drug Delivery System

    PubMed Central

    Chou, Joshua; Ito, Tomoko; Bishop, David; Otsuka, Makoto; Ben-Nissan, Besim; Milthorpe, Bruce

    2013-01-01

    Simvastatin have been shown to induce bone formation and there is currently a urgent need to develop an appropriate delivery system to sustain the release of the drug to increase therapeutic efficacy whilst reducing side effects. In this study, a novel drug delivery system for simvastatin by means of hydrothermally converting marine exoskeletons to biocompatible beta-tricalcium phosphate was investigated. Furthermore, the release of simvastatin was controlled by the addition of an outer apatite coating layer. The samples were characterized by x-ray diffraction analysis, fourier transform infrared spectroscopy, scanning electron microscopy and mass spectroscopy confirming the conversion process. The in-vitro dissolution of key chemical compositional elements and the release of simvastatin were measured in simulated body fluid solution showing controlled release with reduction of approximately 25% compared with un-coated samples. This study shows the potential applications of marine structures as a drug delivery system for simvastatin. PMID:23349949

  19. Tunable biphasic drug release from ethyl cellulose nanofibers fabricated using a modified coaxial electrospinning process

    NASA Astrophysics Data System (ADS)

    Li, Chen; Wang, Zhuan-Hua; Yu, Deng-Guang; Williams, Gareth R.

    2014-05-01

    This manuscript reports a new type of drug-loaded core-shell nanofibers that provide tunable biphasic release of quercetin. The nanofibers were fabricated using a modified coaxial electrospinning process, in which a polyvinyl chloride (PVC)-coated concentric spinneret was employed. Poly (vinyl pyrrolidone) (PVP) and ethyl cellulose (EC) were used as the polymer matrices to form the shell and core parts of the nanofibers, respectively. Scanning and transmission electron microscopy demonstrated that the nanofibers had linear morphologies and core-shell structures. The quercetin was found to be present in the nanofibers in the amorphous physical status, on the basis of X-ray diffraction results. In vitro release profiles showed that the PVP shell very rapidly freed its drug cargo into the solution, while the EC core provided the succedent sustained release. Variation of the drug loading permitted the release profiles to be tuned.

  20. Tunable biphasic drug release from ethyl cellulose nanofibers fabricated using a modified coaxial electrospinning process.

    PubMed

    Li, Chen; Wang, Zhuan-Hua; Yu, Deng-Guang; Williams, Gareth R

    2014-01-01

    This manuscript reports a new type of drug-loaded core-shell nanofibers that provide tunable biphasic release of quercetin. The nanofibers were fabricated using a modified coaxial electrospinning process, in which a polyvinyl chloride (PVC)-coated concentric spinneret was employed. Poly (vinyl pyrrolidone) (PVP) and ethyl cellulose (EC) were used as the polymer matrices to form the shell and core parts of the nanofibers, respectively. Scanning and transmission electron microscopy demonstrated that the nanofibers had linear morphologies and core-shell structures. The quercetin was found to be present in the nanofibers in the amorphous physical status, on the basis of X-ray diffraction results. In vitro release profiles showed that the PVP shell very rapidly freed its drug cargo into the solution, while the EC core provided the succedent sustained release. Variation of the drug loading permitted the release profiles to be tuned. PMID:24940180

  1. Cytotoxicity of release products from magnetic nanocomposites in targeted drug delivery.

    PubMed

    Wamocha, H L; Misak, H E; Song, Z; Chu, H Y; Chen, Y Y; Asmatulu, R; Yang, S-Y; Ho, J C

    2013-02-01

    The efficacy of chemotherapy can be significantly improved if the therapeutic agent remains localized at the afflicted area and released at controlled rates. Such a targeted drug delivery can be achieved using magnetic nanocomposite (MNC), which incorporates drug and magnetic nanoparticles in biodegradable polymer microspheres. Reported here are results from an in vitro study on drug release rate and cytotoxicity of other release products from MNC. The model system contains an anti-cancer chemotherapy agent 5-flurouracil (5-FU) and (Co(0.5)Zn(0.5))Fe(2)O(4) in poly(lactic-co-glycolic acid) (PLGA) matrix produced by an oil/oil emulsion technique. Cell proliferation data indicate a sustained release of 5-FU for mouse macrophage cell eradication, whereas other microsphere components of magnetic nanoparticles and PLGA have little cytotoxic effects. PMID:22071353

  2. Tunable biphasic drug release from ethyl cellulose nanofibers fabricated using a modified coaxial electrospinning process

    PubMed Central

    2014-01-01

    This manuscript reports a new type of drug-loaded core-shell nanofibers that provide tunable biphasic release of quercetin. The nanofibers were fabricated using a modified coaxial electrospinning process, in which a polyvinyl chloride (PVC)-coated concentric spinneret was employed. Poly (vinyl pyrrolidone) (PVP) and ethyl cellulose (EC) were used as the polymer matrices to form the shell and core parts of the nanofibers, respectively. Scanning and transmission electron microscopy demonstrated that the nanofibers had linear morphologies and core-shell structures. The quercetin was found to be present in the nanofibers in the amorphous physical status, on the basis of X-ray diffraction results. In vitro release profiles showed that the PVP shell very rapidly freed its drug cargo into the solution, while the EC core provided the succedent sustained release. Variation of the drug loading permitted the release profiles to be tuned. PMID:24940180

  3. Stimuli-free programmable drug release for combination chemo-therapy.

    PubMed

    Fan, Li; Jin, Boquan; Zhang, Silu; Song, Chaojun; Li, Quan

    2016-07-01

    Combinational chemotherapy capable of targeted delivery and programmable multi-drug release leads to enhanced drug efficacy, and is highly desired for cancer treatment. However, effective approaches for achieving both features in a single treatment are limited. In the present work, we demonstrated programmed delivery of both chemotherapeutic and immunotherapeutic agents with tumor cell targeting capability by using SiO2 based self-decomposable nanoparticulate systems. The programmable drug delivery is realized by manipulating drug loading configurations instead of relying on external stimuli. Both in vitro and in vivo results showed specific drug binding to FAT1-expressing colon cancer cells. The loaded dual drugs were demonstrated to be delivered in a sequential manner with specific time intervals between their peak releases, which maximize the synergistic effect of the chemotherapeutics. These features led to significantly enhanced drug efficacy and reduced system toxicity. The tumor weight decreased by 1/350, together with a moderate increase in rats' body weight, which were observed when adopting the dual drug loaded nanoparticles, as compared to those of the control groups. The present system provides a simple and feasible method for the design of targeting and combination chemotherapy with programmed drug release. PMID:26554664

  4. A Novel Microbubble Capable of Ultrasound-Triggered Release of Drug-Loaded Nanoparticles.

    PubMed

    Wang, Jiayu; Li, Pan; Tian, Rui; Hu, Wenjing; Zhang, Yuxia; Yuan, Pei; Tang, Yalan; Jia, Yuntao; Zhang, Liangke

    2016-03-01

    Drug-loaded microbubbles have shown attractive potential in disease treatment applications. The present work presents a unique ultrasound (US)-triggered system in which drug-loaded nanoparticles and perfluorocarbon gas are encapsulated within the internal space of microbubbles. The prepared curcumin-loaded albumin nanoparticle payload microbubbles (CcmANP-MB) exhibited a mean diameter of 4895.1 nm ± 421.2 nm and a drug-loading efficiency of 2.23% ± 0.08% (297% increase compared with the drug loading of common drug-loaded microbubbles). US allowed the release of the internal payload. In vitro US-triggered drug release experiments showed that the drug release of CcmANP-MB was delayed by lipid membranes and significantly increased after sonication. In vitro and in vivo US imaging experiments demonstrated that CcmANP-MB evidently enhances US imaging, which indicates that the microbubbles possess good acoustic properties even after encapsulation of nanoparticles. Tumor bearing mice were administered with CcmANP-MB through the tail vein and were then exposed to ultrasound, which resulted in an enhanced drug accumulation in tumor tissues and a significant increase in tumor growth inhibition rate (57.1%) compared with CcmANP-MB alone (28.8%) as well as curcumin-loaded albumin nanoparticle (26.2%). Therefore, the combination of lecithin microbubbles and albumin nanoparticles provides a platform for targeted drug delivery in clinical therapy and disease diagnosis. PMID:27280249

  5. Effect of Different Polymer Concentration on Drug Release Rate and Physicochemical Properties of Mucoadhesive Gastroretentive Tablets

    PubMed Central

    Agarwal, Shweta; Murthy, R. S. R.

    2015-01-01

    Mucoadhesive tablets have emerged as potential candidates for gastroretentive drug delivery providing controlled release along with prolonged gastric residence time. Gastroretentive mucoadhesive tablets could result in increased bioavailability due to prolonged gastric residence time. A hydrophilic matrix system was developed as mucoadhesion is achievable on appropriate wetting and swelling of the polymers used. The polymers were so chosen so as to provide a balance between swelling, mucoadhesion and drug release. The polymers chosen were hydroxypropyl methylcellulose K4M, chitosan, and Carbopol 934. The concentrations of these polymers used has a great impact on the physicochemical properties of the resulting formulation. The tablets were formulated using wet granulation method and tranexamic acid was used as the model drug. The prepared tablets were characterized for size, shape, appearance, hardness, friability, weight variation, swelling, mucoadhesion and in vitro drug release. Several batches of tablets were prepared by varying the ratio of hydroxypropyl methylcellulose K4M and Chitosan. The batches having a greater ratio of chitosan showed higher rate of swelling, greater erosion, less mucoadhesion and faster release rate of the drug whereas the batches having greater ratio of hydroxypropyl methylcellulose K4M showed lesser rate of swelling, less erosion, better mucoadhesion and a smaller drug release rate. The level of carbopol was kept constant in all the batches. PMID:26997698

  6. Effect of Different Polymer Concentration on Drug Release Rate and Physicochemical Properties of Mucoadhesive Gastroretentive Tablets.

    PubMed

    Agarwal, Shweta; Murthy, R S R

    2015-01-01

    Mucoadhesive tablets have emerged as potential candidates for gastroretentive drug delivery providing controlled release along with prolonged gastric residence time. Gastroretentive mucoadhesive tablets could result in increased bioavailability due to prolonged gastric residence time. A hydrophilic matrix system was developed as mucoadhesion is achievable on appropriate wetting and swelling of the polymers used. The polymers were so chosen so as to provide a balance between swelling, mucoadhesion and drug release. The polymers chosen were hydroxypropyl methylcellulose K4M, chitosan, and Carbopol 934. The concentrations of these polymers used has a great impact on the physicochemical properties of the resulting formulation. The tablets were formulated using wet granulation method and tranexamic acid was used as the model drug. The prepared tablets were characterized for size, shape, appearance, hardness, friability, weight variation, swelling, mucoadhesion and in vitro drug release. Several batches of tablets were prepared by varying the ratio of hydroxypropyl methylcellulose K4M and Chitosan. The batches having a greater ratio of chitosan showed higher rate of swelling, greater erosion, less mucoadhesion and faster release rate of the drug whereas the batches having greater ratio of hydroxypropyl methylcellulose K4M showed lesser rate of swelling, less erosion, better mucoadhesion and a smaller drug release rate. The level of carbopol was kept constant in all the batches. PMID:26997698

  7. A mathematical model of drug release from liposomes by low frequency ultrasound.

    PubMed

    Enden, Giora; Schroeder, Avi

    2009-12-01

    Administration of drugs using small (<100 nm) unilamellar liposomes enables effective targeting of tumors and inflamed tissue. Therapeutic efficacy may be enhanced by triggering liposomal drug release in the desired organ in a controlled manner using a noninvasive external signal. Previous studies have demonstrated that low frequency ultrasound (LFUS) can be used to control the release of drugs from liposomes. LFUS irradiation has a twofold effect: (1) it causes the impermeable liposome membrane to become permeable and (2) it induces liposome disintegration. Immediately upon cessation of LFUS irradiation the membrane resumes its impermeable state and liposome disintegration stops. The mathematical model presented here is aimed at providing a better quantitative and qualitative understanding of LFUS-induced liposomal drug release, which is essential for safe and effective implementation of this technique. The time-dependent release patterns are determined by the liposome disintegration patterns and by two key parameters: (a) the average permeability of the membrane to the drug and (b) the ratio between the volume of the entire dispersion and the initial volume of all the liposomes in the dispersion. The present model implies that LFUS irradiation triggers two liposomal drug-release mechanisms: the predominant one is diffusion through the LFUS-compromised liposome membrane, and the less significant one is liposome disintegration. PMID:19731036

  8. Multi-Drug-Loaded Microcapsules with Controlled Release for Management of Parkinson's Disease.

    PubMed

    Baek, Jong-Suep; Choo, Chee Chong; Qian, Cheng; Tan, Nguan Soon; Shen, Zexiang; Loo, Say Chye Joachim

    2016-07-01

    Parkinson's disease (PD) is a progressive disease of the nervous system, and is currently managed through commercial tablets that do not sufficiently enable controlled, sustained release capabilities. It is hypothesized that a drug delivery system that provides controlled and sustained release of PD drugs would afford better management of PD. Hollow microcapsules composed of poly-l-lactide (PLLA) and poly (caprolactone) (PCL) are prepared through a modified double-emulsion technique. They are loaded with three PD drugs, i.e., levodopa (LD), carbidopa (CD), and entacapone (ENT), at a ratio of 4:1:8, similar to commercial PD tablets. LD and CD are localized in both the hollow cavity and PLLA/PCL shell, while ENT is localized in the PLLA/PCL shell. Release kinetics of hydrophobic ENT is observed to be relatively slow as compared to the other hydrophilic drugs. It is further hypothesized that encapsulating ENT into PCL as a surface coating onto these microcapsules can aid in accelerating its release. Now, these spray-coated hollow microcapsules exhibit similar release kinetics, according to Higuchi's rate, for all three drugs. The results suggest that multiple drug encapsulation of LD, CD, and ENT in gastric floating microcapsules could be further developed for in vivo evaluation for the management of PD. PMID:27253884

  9. Electrospun upconversion composite fibers as dual drugs delivery system with individual release properties.

    PubMed

    Hou, Zhiyao; Li, Xuejiao; Li, Chunxia; Dai, Yunlu; Ma, Ping'an; Zhang, Xiao; Kang, Xiaojiao; Cheng, Ziyong; Lin, Jun

    2013-07-30

    Novel multifunctional poly(ε-caprolactone)-gelatin encapsulating upconversion core/shell silica nanoparticles (NPs) composite fibers as dual drugs delivery system (DDDS), with indomethacin (IMC) and doxorubicin (DOX) releasing in individual release properties, have been designed and fabricated via electrospinning process. Uniform and monodisperse upconversion (UC) luminescent NaYF4:Yb(3+), Er(3+) nanocrystals (UCNCs) were encapsulated with mesoporous silica shells, resulting in the formation of core/shell structured NaYF4:Yb(3+), Er(3+)@mSiO2 (UCNCs@mSiO2) NPs, which can be performed as DOX delivery carriers. These UCNCs@mSiO2 NPs loading DOX then were dispersed into the mixture of poly(ε-caprolactone) (PCL) and gelatin-based electrospinning solution containing IMC, followed by the preparation of dual drug-loaded composite fibers (DDDS) via electrospinning method. The drugs release profiles of the DDDS were measured, and the results indicated that the IMC and DOX released from the electrospun composite fibers showed distinct properties. The IMC in the composite fibers presented a fast release manner, while DOX showed a sustained release behavior. Moreover, the UC luminescent intensity ratios of (2)H(11/2)/(4)S(3/2)-(4)I(15/2) to (4)F(9/2)-(4)I(15/2) from Er(3+) vary with the amounts of DOX in the system, and thus drug release can be tracked and monitored by the luminescence resonance energy transfer (LRET) mechanism. PMID:23855606

  10. Polymer excipients enable sustained drug release in low pH from mechanically strong inorganic geopolymers.

    PubMed

    Jämstorp, Erik; Yarra, Tejaswi; Cai, Bing; Engqvist, Håkan; Bredenberg, Susanne; Strømme, Maria

    2012-01-01

    Improving acid resistance, while maintaining the excellent mechanical stability is crucial in the development of a sustained and safe oral geopolymer dosage form for highly potent opioids. In the present work, commercially available Methacrylic acid-ethyl acrylate copolymer, Polyethylene-glycol (PEG) and Alginate polymer excipients were included in dissolved or powder form in geopolymer pellets to improve the release properties of Zolpidem, herein acting as a model drug for the highly potent opioid Fentanyl. Scanning electron microscopy, compression strength tests and drug release experiments, in gastric pH 1 and intestinal pH 6.8 conditions, were performed. The polymer excipients, with an exception for PEG, reduced the drug release rate in pH 1 due to their ability to keep the pellets in shape, in combination with the introduction of an insoluble excipient, and thereby maintain a barrier towards drug diffusion and release. Neither geopolymer compression strength nor the release in pH 6.8 was considerably impaired by the incorporation of the polymer excipients. The geopolymer/polymer composites combine high mechanical strength and good release properties under both gastric and intestinal pH conditions, and are therefore promising oral dosage forms for sustained release of highly potent opioids. PMID:25755991

  11. Polymer excipients enable sustained drug release in low pH from mechanically strong inorganic geopolymers

    PubMed Central

    Jämstorp, Erik; Yarra, Tejaswi; Cai, Bing; Engqvist, Håkan; Bredenberg, Susanne; Strømme, Maria

    2012-01-01

    Improving acid resistance, while maintaining the excellent mechanical stability is crucial in the development of a sustained and safe oral geopolymer dosage form for highly potent opioids. In the present work, commercially available Methacrylic acid–ethyl acrylate copolymer, Polyethylene-glycol (PEG) and Alginate polymer excipients were included in dissolved or powder form in geopolymer pellets to improve the release properties of Zolpidem, herein acting as a model drug for the highly potent opioid Fentanyl. Scanning electron microscopy, compression strength tests and drug release experiments, in gastric pH 1 and intestinal pH 6.8 conditions, were performed. The polymer excipients, with an exception for PEG, reduced the drug release rate in pH 1 due to their ability to keep the pellets in shape, in combination with the introduction of an insoluble excipient, and thereby maintain a barrier towards drug diffusion and release. Neither geopolymer compression strength nor the release in pH 6.8 was considerably impaired by the incorporation of the polymer excipients. The geopolymer/polymer composites combine high mechanical strength and good release properties under both gastric and intestinal pH conditions, and are therefore promising oral dosage forms for sustained release of highly potent opioids. PMID:25755991

  12. Ofloxacin Loaded Electrospun Fibers for Ocular Drug Delivery: Effect of Formulation Variables on Fiber Morphology and Drug Release.

    PubMed

    Karataş, Ayşegül; Algan, Aslihan Hilal; Pekel-Bayramgil, Nursel; Turhan, Fatih; Altanlar, Nurten

    2016-01-01

    Ofloxacin (OFL) loaded poly(ε-caprolactone) (PCL) and PCL: poly(butylene succinate) PBS fibers as a drug delivery system in the treatment of ocular infections were prepared by electrospinning. In particular, the effect of some formulation variables including polymer:drug ratio (9:1, 8:2 and 7:3 w/w), solvent systems like dichloromethane (DCM), N,N-dimethylformamide (DMF), N,Ndimethylacetamide (DMAc) and dimethylsulfoxide (DMSO), polymer blends of PCL:PBS at 80:20, 60:40 and 40:60 ratios on fiber morphology, fiber size were investigated. The morphology and diameter of the electrospun fibers were investigated by scanning electron microscopy (SEM) images also the thermal properties were evaluated by differential scanning calorimetry (DSC). The drug release behaviour from fibers and in vitro antibacterial activity were also studied. It was noticed that the average fiber diameter decreased with decreasing polymer amount in initial composition meanwhile the release of drug increased with increasing amount of drug in formulations. Solvent system of DCM:DMF at 80:20 ratio improved fiber morphology and resulted in a reduction in fiber diameter. It was found that smooth surface, flexible fibers with uniform morphology were obtained with 80:20 ratio of PCL:PBS compositions. All fibers showed a burst release of OFL. The initial amount of the released OFL was found to vary as a function of PCL:OFL ratio and polymer composition in the fiber. The microbiological activity of optimized formulation was evaluated using P. aeruginosa, S. epidermidis, S. Aureus and E. coli strains and the results of this study clearly demonstrated that freely released OFL from fibers inhibited the growth of the tested bacteria. The process of electrospinning had no adverse effect on the activity of incorporated drug in fibers. PMID:26521656

  13. Extracellular control of intracellular drug release for enhanced safety of anti-cancer chemotherapy

    NASA Astrophysics Data System (ADS)

    Zhu, Qian; Qi, Haixia; Long, Ziyan; Liu, Shang; Huang, Zhen; Zhang, Junfeng; Wang, Chunming; Dong, Lei

    2016-06-01

    The difficulty of controlling drug release at an intracellular level remains a key challenge for maximising drug safety and efficacy. We demonstrate herein a new, efficient and convenient approach to extracellularly control the intracellular release of doxorubicin (DOX), by designing a delivery system that harnesses the interactions between the system and a particular set of cellular machinery. By simply adding a small-molecule chemical into the cell medium, we could lower the release rate of DOX in the cytosol, and thereby increase its accumulation in the nuclei while decreasing its presence at mitochondria. Delivery of DOX with this system effectively prevented DOX-induced mitochondria damage that is the main mechanism of its toxicity, while exerting the maximum efficacy of this anti-cancer chemotherapeutic agent. The present study sheds light on the design of drug delivery systems for extracellular control of intracellular drug delivery, with immediate therapeutic implications.

  14. Extracellular control of intracellular drug release for enhanced safety of anti-cancer chemotherapy

    PubMed Central

    Zhu, Qian; Qi, Haixia; Long, Ziyan; Liu, Shang; Huang, Zhen; Zhang, Junfeng; Wang, Chunming; Dong, Lei

    2016-01-01

    The difficulty of controlling drug release at an intracellular level remains a key challenge for maximising drug safety and efficacy. We demonstrate herein a new, efficient and convenient approach to extracellularly control the intracellular release of doxorubicin (DOX), by designing a delivery system that harnesses the interactions between the system and a particular set of cellular machinery. By simply adding a small-molecule chemical into the cell medium, we could lower the release rate of DOX in the cytosol, and thereby increase its accumulation in the nuclei while decreasing its presence at mitochondria. Delivery of DOX with this system effectively prevented DOX-induced mitochondria damage that is the main mechanism of its toxicity, while exerting the maximum efficacy of this anti-cancer chemotherapeutic agent. The present study sheds light on the design of drug delivery systems for extracellular control of intracellular drug delivery, with immediate therapeutic implications. PMID:27334142

  15. Abuse of Prescription (Rx) Drugs Affects Young Adults Most

    MedlinePlus

    ... Trends and Alerts Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Prescription ... died from overdoses of any other drug, including heroin and cocaine combined—and many more needed emergency ...

  16. [Evolution of oral drug forms of metoprolol: advantages of long acting modified release forms with modified release].

    PubMed

    Leonova, M V; Maneshina, O A; Belousov, Iu B

    2010-01-01

    Review oral modified release drug forms of beta-adrenoblocker metoprolol which is used in arterial hypertension and ischemic heart disease is presented. Metoprolol has salts such as tartrate which is used for production of immediate release (IR) and sustained release (SR) forms and succinate used for production of controlled release form (CR/XL). Metoprolol SR has monolith matrix type, metoprolol CR/XL-system of multiple pellets. Effect of metoprolol tartrate (IR) on mortality was demonstrated in a number of studies in patients with arterial hypertension (AH) (MAPHY), myocardial infarction (SMT, GMT, MIAMI), dilated cardiomyopathy and heart failure (MDC). Studies of efficacy of metoprolol SR are scarce. Antihypertensive efficacy of metoprolol SR in patients with AH did not exceed that of a metoprolol IR or CR/XL. First retrospective analysis of efficacy of metoprolol tartrate and succinate (CR/XL) in patients after myocardial infarction allowed to obtain comparable results of 34% mortality lowering. In a prospective study in patients with chronic heart failure (COMET) metoprolol tartrate IR was not superior to carvedilol when mortality lowering was concerned. At the same time administration of controlled release metoprolol (CR/XL) in 2 large clinical trials (RESOLVD, MERITAHF) was advantageous in patients with chronic heart failure relative to lowering of mortality and rate of hospitalizations. A novel controlled release form of metoprolol has been created as a tartrate salt on the basis of pellet technology (CD/ERT) and its bioequivalence to metoprolol CR/XL has been proved. PMID:21591398

  17. Overview of processes affecting contaminant release from confined disposal facilities. Final report

    SciTech Connect

    Martin, J.L.; McCutcheon, S.C.

    1992-01-01

    Confined disposal facilities (CDFs) are widely used for the disposal of dredged material from Corps of Engineers maintenance dredging projects along the Atlantic and Gulf coasts and waterways and harbors in the Great Lakes. CDFs are a less common disposal alternative along the Pacific coast and inland river systems. When contaminated dredged material is placed in the CDF, there is a potential for contaminant mobilization and release from the CDF by a variety of physical, chemical, and biological processes. This report provides an overview of the processes affecting mobilization and release of contaminants from CDFs and the potential applicability of multimedia models for prediction of contaminant release. Processes affecting release from in-water CDFs are emphasized, although many of the processes discussed are applicable to nearshore and upland CDFs. Processes affecting contaminant release are complex, involving a variety of chemicals and operational and design considerations. Many of the important processes are reasonably well known. Laboratory column settling and elutriate techniques have been developed to estimate solids and contaminant concentration in water directly released during hydraulic disposal operations. Predictive techniques for other processes are not as available.

  18. Diffusion-Controlled Drug Release From the Mesoporous Magnesium Carbonate Upsalite(®).

    PubMed

    Zhang, Peng; Zardán Gómez de la Torre, Teresa; Forsgren, Johan; Bergström, Christel A S; Strømme, Maria

    2016-02-01

    In vitro drug release from well-defined particle-size fractions of the mesoporous magnesium carbonate material Upsalite(®) was investigated in detail using ibuprofen, a biopharmaceutics classification system class II drug, as the model compound. The weight of loaded drug corresponded to 30% of the weight of the carrier and the pores were filled to approximately 80%. The incorporated ibuprofen was found to be in an amorphous state and was physisorbed, rather than chemisorbed, to the surfaces of the pore walls. In contrast to ibuprofen in mesoporous silica, there was no detectable drug on the outer surface of the carrier particles. Two ibuprofen doses were loaded into Upsalite(®) particles with size fractions ranging from 25 μm to more than 200 μm. The initial release rate was controlled by the particle size; the dissolution rate of the loaded ibuprofen during this period was more than four times faster than that of the crystalline drug. An extended-release period of about 24 h followed the initial rapid-release period. The features of this extended-release period were dependent on the total drug concentration in the release medium. Detailed analysis of the diffusion of ibuprofen in Upsalite(®) provided the ibuprofen diffusion coefficient (9.8 × 10(-8) cm(2)/s), the constrictivity of the diffusion process (0.47) and the tortuosity of the carrier (15). This relatively high tortuosity value indicates that Upsalite(®) can be used not only to enhance the dissolution rate of poorly soluble drugs but also as a carrier in sustained-release applications by using larger particle sizes or even pellets of the material. PMID:26087956

  19. Meeting the Special Needs of Drug-Affected Children. ERIC Digest Series Number EA 53.

    ERIC Educational Resources Information Center

    Lumsden, Linda S.

    Issues pertinent to prenatal drug-affected students are discussed in this ERIC Digest. The rising number of drug-exposed children approaching school age presents a challenge to school personnel in meeting their special needs. Topics covered are: (1) seriousness of the problem; (2) problems unique to drug-affected children; (3) creation of a…

  20. Release of a Poorly Soluble Drug from Hydrophobically Modified Poly (Acrylic Acid) in Simulated Intestinal Fluids

    PubMed Central

    Knöös, Patrik

    2015-01-01

    A large part of new pharmaceutical substances are characterized by a poor solubility and high hydrophobicity, which might lead to a difference in drug adsorption between fasted and fed patients. We have previously evaluated the release of hydrophobic drugs from tablets based on Pemulen TR2 and showed that the release can be manipulated by adding surfactants. Here we further evaluate the possibility to use Pemulen TR2 in controlled release tablet formulations containing a poorly soluble substance, griseofulvin. The release is evaluated in simulated intestinal media that model the fasted state (FaSSIF medium) or fed state (FeSSIF). The rheology of polymer gels is studied in separate experiments, in order to gain more information on possible interactions. The release of griseofulvin in tablets without surfactant varied greatly and the slowest release were observed in FeSSIF. Addition of SDS to the tablets eliminated the differences and all tablets showed a slow linear release, which is of obvious relevance for robust drug delivery. Comparing the data from the release studies and the rheology experiment showed that the effects on the release from the different media could to a large extent be rationalised as a consequence of the interactions between the polymer and the surfactants in the media. The study shows that Pemulen TR2 is a candidate for controlled release formulations in which addition of surfactant provides a way to eliminate food effects on the release profile. However, the formulation used needs to be designed to give a faster release rate than the tablets currently investigated. PMID:26473964

  1. Release of a Poorly Soluble Drug from Hydrophobically Modified Poly (Acrylic Acid) in Simulated Intestinal Fluids.

    PubMed

    Knöös, Patrik; Svensson, Anna V; Ulvenlund, Stefan; Wahlgren, Marie

    2015-01-01

    A large part of new pharmaceutical substances are characterized by a poor solubility and high hydrophobicity, which might lead to a difference in drug adsorption between fasted and fed patients. We have previously evaluated the release of hydrophobic drugs from tablets based on Pemulen TR2 and showed that the release can be manipulated by adding surfactants. Here we further evaluate the possibility to use Pemulen TR2 in controlled release tablet formulations containing a poorly soluble substance, griseofulvin. The release is evaluated in simulated intestinal media that model the fasted state (FaSSIF medium) or fed state (FeSSIF). The rheology of polymer gels is studied in separate experiments, in order to gain more information on possible interactions. The release of griseofulvin in tablets without surfactant varied greatly and the slowest release were observed in FeSSIF. Addition of SDS to the tablets eliminated the differences and all tablets showed a slow linear release, which is of obvious relevance for robust drug delivery. Comparing the data from the release studies and the rheology experiment showed that the effects on the release from the different media could to a large extent be rationalised as a consequence of the interactions between the polymer and the surfactants in the media. The study shows that Pemulen TR2 is a candidate for controlled release formulations in which addition of surfactant provides a way to eliminate food effects on the release profile. However, the formulation used needs to be designed to give a faster release rate than the tablets currently investigated. PMID:26473964

  2. Chronic treatment with anti-bipolar drugs suppresses glutamate release from astroglial cultures.

    PubMed

    Liu, Zhuo; Song, Dan; Yan, Enzhi; Verkhratsky, Alexei; Peng, Liang

    2015-05-01

    Astroglial cells are fundamental elements of most neurological diseases, including bipolar disorders in which astrocytes show morphological and functional deficiency. Here we report the suppression of astroglial glutamate release by chronic treatment with three anti-bipolar drugs, lithium salt (Li(+)), carbamazepine (CBZ) and valproic acid (VPA). Release of glutamate was triggered by transient exposure of astrocytes to ATP (which activated purinoceptors) and 45 mM K(+) (which depolarised cell membrane to ~-30 mV). In both types of stimulation glutamate release was regulated by Ca(2+) entry through plasmalemmal channels and by Ca(2+) release from the endoplasmic reticulum (ER) intracellular stores. Exposure of astroglial cultures to Li(+), CBZ and VPA for 2 weeks led to a significant (more than 2 times) inhibition of glutamate release, which may alleviate the hyperactivity of the glutamatergic transmission in the brain of patients with bipolar disorders and thus contribute the underlying mechanism of drug action. PMID:25676933

  3. Drug release assays from new chitosan/pHEMA membranes obtained by gamma irradiation

    NASA Astrophysics Data System (ADS)

    Casimiro, M. H.; Gil, M. H.; Leal, J. P.

    2007-12-01

    With the purpose of obtaining a biocompatible and microbiologically safe matrix that simultaneously could be used as wound dressing material and as a controlled drug release system, membranes with different thickness and different contents in chitosan and hydroxyethyl methacrylate (HEMA) have been prepared by γ irradiation from a 60Co source. Antibiotic release experiments were performed before or after irradiation over amoxicillin loaded chitosan/pHEMA membranes in physiological saline solution, and monitored by UV-Vis spectrometry. Results point out a fast amoxicillin release with similar release profile in all studied membranes. The amount of released drug was shown to be dependent on membranes network crosslinking due composition, radiation and membrane thickness.

  4. Effects of interfacial layer wettability and thickness on the coating morphology and sirolimus release for drug-eluting stent.

    PubMed

    Bedair, Tarek M; Yu, Seung Jung; Im, Sung Gap; Park, Bang Ju; Joung, Yoon Ki; Han, Dong Keun

    2015-12-15

    Drug-eluting stents (DESs) have been used to treat coronary artery diseases by placing in the arteries. However, current DESs still suffer from polymer coating defects such as delamination and peeling-off that follows stent deployment. Such coating defects could increase the roughness of DES and might act as a source of late or very late thrombosis and might increase the incident of restenosis. In this regard, we modified the cobalt-chromium (Co-Cr) alloy surface with hydrophilic poly(2-hydroxyethyl methacrylate) (PHEMA) or hydrophobic poly(2-hydroxyethyl methacrylate)-grafted-poly(caprolactone) (PHEMA-g-PCL) brushes. The resulting surfaces were biocompatible and biodegradable, which could act as anchoring layer for the drug-in-polymer matrix coating. The two modifications were characterized by ATR-FTIR, XPS, water contact angle measurements, SEM and AFM. On the control and modified Co-Cr samples, a sirolimus (SRL)-containing poly(D,L-lactide) (PDLLA) were ultrasonically spray-coated, and the drug release was examined for 8weeks under physiological conditions. The results demonstrated that PHEMA as a primer coating improved the coating stability and degradation morphology, and drug release profile for short-term as compared to control Co-Cr, but fails after 7weeks in physiological buffer. On the other hand, the hydrophobic PHEMA-g-PCL brushes not only enhanced the stability and degradation morphology of the PDLLA coating layer, but also sustained SRL release for long-term. At 8-week of release test, the surface morphologies and release profiles of coated PDLLA layers verified the beneficial effect of hydrophobic PCL brushes as well as their thickness on coating stability. Our study concludes that 200nm thickness of PHEMA-g-PCL as interfacial layer affects the stability and degradation morphology of the biodegradable coating intensively to be applied for various biodegradable-based DESs. PMID:26319336

  5. Antibiotic-loaded chitosan-Laponite films for local drug delivery by titanium implants: cell proliferation and drug release studies.

    PubMed

    Ordikhani, Farideh; Dehghani, Mehdi; Simchi, Arash

    2015-12-01

    In this study, chitosan-Laponite nanocomposite coatings with bone regenerative potential and controlled drug-release capacity are prepared by electrophoretic deposition technique. The controlled release of a glycopeptide drug, i.e. vancomycin, is attained by the intercalation of the polymer and drug macromolecules into silicate galleries. Fourier-transform infrared spectrometry reveals electrostatic interactions between the charged structure of clay and the amine and hydroxyl groups of chitosan and vancomycin, leading to a complex positively-charged system with high electrophoretic mobility. By applying electric field the charged particles are deposited on the surface of titanium foils and uniform chitosan films containing 25-55 wt% Laponite and 937-1655 µg/cm(2) vancomycin are obtained. Nanocomposite films exhibit improved cell attachment with higher cell viability. Alkaline phosphatase assay reveals enhanced cell proliferation due the gradual dissolution of Laponite particles into the culture medium. In-vitro drug-release studies show lower release rate through a longer period for the nanocomposite compared to pristine chitosan. PMID:26507202

  6. Multifluorescently traceable nanoparticle by a single-wavelength excitation with color-related drug release performance.

    PubMed

    Lu, Deli; Lei, Juying; Wang, Lingzhi; Zhang, Jinlong

    2012-05-30

    Monodisperse and nanometer-sized periodic mesoporous organosilicas co-doped with fluorescence resonance energy transfer cascades composed of triple fluorophores at various ratios were prepared. These nanoparticles exhibit multifluorescent emissions by a single-wavelength excitation and were designed for the application as multichannelly traceable drug carriers. Different from the hydrophilic framework of inorganic mesoporous silica and hydrophobic framework of mesoporous carbon, these multifluorescent nanoparticles have intrinsically different and finely tunable pore surface polarities governed by the type and amount of fluorophore inside the framework. When applied as drug carriers, they can achieve synchronous or asynchronous release of different drugs by simply choosing different colored nanoparticles. These colorful mesoporous composites with finely tunable color-related drug release performance provide a strong barcoding system for the potential applications of fluorescent nanoparticles in effective screening of drugs and therapeutic protocols for diseases. PMID:22591275

  7. The affective dimension of pain as a risk factor for drug and alcohol addiction.

    PubMed

    LeBlanc, Dana M; McGinn, M Adrienne; Itoga, Christy A; Edwards, Scott

    2015-12-01

    Addiction, or substance use disorder (SUD), is a devastating psychiatric disease composed of multiple elemental features. As a biobehavioral disorder, escalation of drug and/or alcohol intake is both a cause and consequence of molecular neuroadaptations in central brain reinforcement circuitry. Multiple mesolimbic areas mediate a host of negative affective and motivational symptoms that appear to be central to the addiction process. Brain stress- and reinforcement-related regions such as the central amygdala (CeA), prefrontal cortex (PFC), and nucleus accumbens (NAc) also serve as central processors of ascending nociceptive input. We hypothesize that a sensitization of brain mechanisms underlying the processing of persistent and maladaptive pain contributes to a composite negative affective state to drive the enduring, relapsing nature of addiction, particularly in the case of alcohol and opioid use disorder. At the neurochemical level, pain activates central stress-related neuropeptide signaling, including the dynorphin and corticotropin-releasing factor (CRF) systems, and by this process may facilitate negative affect and escalated drug and alcohol use over time. Importantly, the widespread prevalence of unresolved pain and associated affective dysregulation in clinical populations highlights the need for more effective analgesic medications with reduced potential for tolerance and dependence. The burgeoning epidemic of prescription opioid abuse also demands a closer investigation into the neurobiological mechanisms of how pain treatment could potentially represent a significant risk factor for addiction in vulnerable populations. Finally, the continuing convergence of sensory and affective neuroscience fields is expected to generate insight into the critical balance between pain relief and addiction liability, as well as provide more effective therapeutic strategies for chronic pain and addiction. PMID:26008713

  8. Quantifying the effect size of changing environmental controls on carbon release from permafrost-affected soils

    NASA Astrophysics Data System (ADS)

    Schaedel, C.; Bader, M. K. F.; Schuur, E. A. G.; Bracho, R. G.; Capek, P.; De Baets, S. L.; Diakova, K.; Ernakovich, J. G.; Hartley, I. P.; Iversen, C. M.; Kane, E. S.; Knoblauch, C.; Lupascu, M.; Natali, S.; Norby, R. J.; O'Donnell, J. A.; Roy Chowdhury, T.; Santruckova, H.; Shaver, G. R.; Sloan, V. L.; Treat, C. C.; Waldrop, M. P.

    2014-12-01

    High-latitude surface air temperatures are rising twice as fast as the global mean, causing permafrost to thaw and thereby exposing large quantities of previously frozen organic carbon (C) to microbial decomposition. Increasing temperatures in high latitude ecosystems not only increase C emissions from previously frozen C in permafrost but also indirectly affect the C cycle through changes in regional and local hydrology. Warmer temperatures increase thawing of ice-rich permafrost, causing land surface subsidence where soils become waterlogged, anoxic conditions prevail and C is released in form of anaerobic CO2 and CH4. Although substrate quality, physical protection, and nutrient availability affect C decomposition, increasing temperatures and changes in surface and sub-surface hydrology are likely the dominant factors affecting the rate and form of C release from permafrost; however, their effect size on C release is poorly quantified. We have compiled a database of 24 incubation studies with soils from active layer and permafrost from across the entire permafrost zone to quantify a) the effect size of increasing temperatures and b) the changes from aerobic to anaerobic environmental soil conditions on C release. Results from two different meta-analyses show that a 10°C increase in temperature increased C release by a factor of two in boreal forest, peatland and tundra ecosystems. Under aerobic incubation conditions, soils released on average three times more C than under anaerobic conditions with large variation among the different ecosystems. While peatlands showed similar amounts of C release under aerobic and anaerobic soil conditions, tundra and boreal forest ecosystems released up to 8 times more C under anoxic conditions. This pan-arctic synthesis shows that boreal forest and tundra soils will have a larger impact on climate change when newly thawed permafrost C decomposes in an aerobic environment compared to an anaerobic environment even when

  9. Influence of drug distribution and solubility on release from geopolymer pellets--a finite element method study.

    PubMed

    Jämstorp, Erik; Strømme, Maria; Bredenberg, Susanne

    2012-05-01

    This study investigates the influence of drug solubility and distribution on its release from inert geopolymer pellets of three different sizes (1.5 × 1.5, 3 × 6, and 6 × 6 mm), having the same geopolymer composition and containing highly potent opioid fentanyl, sumatriptan, theophylline, or saccharin. Scanning electron microscopy, nitrogen sorption, drug solubility, permeation, and release experiments were performed, and estimates of the drug diffusion coefficients and solubilities in the geopolymer matrix were derived with the aid of finite element method (FEM). FEM was further employed to investigate the effect of a nonuniform drug distribution on the drug release profile. When inspecting the release profiles for each drug, it was observed that their solubilities in the geopolymer matrix imposed a much greater influence on the drug release rate than their diffusion coefficients. Concentrating the initial drug load in FEM into nonuniformly distributed drug regions inside the matrix created drug release profiles that more closely resembled experimental data than an FEM-simulated uniform drug distribution did. The presented FEM simulations and visualization of drug release from geopolymers under varying initial and dynamic conditions should open up for more systematic studies of additional factors that influence the drug release profile from porous delivery vehicles. PMID:22308066

  10. Bioerodable PLGA-Based Microparticles for Producing Sustained-Release Drug Formulations and Strategies for Improving Drug Loading

    PubMed Central

    Han, Felicity Y.; Thurecht, Kristofer J.; Whittaker, Andrew K.; Smith, Maree T.

    2016-01-01

    Poly(lactic-co-glycolic acid) (PLGA) is the most widely used biomaterial for microencapsulation and prolonged delivery of therapeutic drugs, proteins and antigens. PLGA has excellent biodegradability and biocompatibility and is generally recognized as safe by international regulatory agencies including the United States Food and Drug Administration and the European Medicines Agency. The physicochemical properties of PLGA may be varied systematically by changing the ratio of lactic acid to glycolic acid. This in turn alters the release rate of microencapsulated therapeutic molecules from PLGA microparticle formulations. The obstacles hindering more widespread use of PLGA for producing sustained-release formulations for clinical use include low drug loading, particularly of hydrophilic small molecules, high initial burst release and/or poor formulation stability. In this review, we address strategies aimed at overcoming these challenges. These include use of low-temperature double-emulsion methods to increase drug-loading by producing PLGA particles with a small volume for the inner water phase and a suitable pH of the external phase. Newer strategies for producing PLGA particles with high drug loading and the desired sustained-release profiles include fabrication of multi-layered microparticles, nanoparticles-in-microparticles, use of hydrogel templates, as well as coaxial electrospray, microfluidics, and supercritical carbon dioxide methods. Another recent strategy with promise for producing particles with well-controlled and reproducible sustained-release profiles involves complexation of PLGA with additives such as polyethylene glycol, poly(ortho esters), chitosan, alginate, caffeic acid, hyaluronic acid, and silicon dioxide. PMID:27445821

  11. Bioerodable PLGA-Based Microparticles for Producing Sustained-Release Drug Formulations and Strategies for Improving Drug Loading.

    PubMed

    Han, Felicity Y; Thurecht, Kristofer J; Whittaker, Andrew K; Smith, Maree T

    2016-01-01

    Poly(lactic-co-glycolic acid) (PLGA) is the most widely used biomaterial for microencapsulation and prolonged delivery of therapeutic drugs, proteins and antigens. PLGA has excellent biodegradability and biocompatibility and is generally recognized as safe by international regulatory agencies including the United States Food and Drug Administration and the European Medicines Agency. The physicochemical properties of PLGA may be varied systematically by changing the ratio of lactic acid to glycolic acid. This in turn alters the release rate of microencapsulated therapeutic molecules from PLGA microparticle formulations. The obstacles hindering more widespread use of PLGA for producing sustained-release formulations for clinical use include low drug loading, particularly of hydrophilic small molecules, high initial burst release and/or poor formulation stability. In this review, we address strategies aimed at overcoming these challenges. These include use of low-temperature double-emulsion methods to increase drug-loading by producing PLGA particles with a small volume for the inner water phase and a suitable pH of the external phase. Newer strategies for producing PLGA particles with high drug loading and the desired sustained-release profiles include fabrication of multi-layered microparticles, nanoparticles-in-microparticles, use of hydrogel templates, as well as coaxial electrospray, microfluidics, and supercritical carbon dioxide methods. Another recent strategy with promise for producing particles with well-controlled and reproducible sustained-release profiles involves complexation of PLGA with additives such as polyethylene glycol, poly(ortho esters), chitosan, alginate, caffeic acid, hyaluronic acid, and silicon dioxide. PMID:27445821

  12. Indocyanine Green-Loaded Liposomes for Light-Triggered Drug Release.

    PubMed

    Lajunen, Tatu; Kontturi, Leena-Stiina; Viitala, Lauri; Manna, Moutusi; Cramariuc, Oana; Róg, Tomasz; Bunker, Alex; Laaksonen, Timo; Viitala, Tapani; Murtomäki, Lasse; Urtti, Arto

    2016-06-01

    Light-triggered drug delivery systems enable site-specific and time-controlled drug release. In previous work, we have achieved this with liposomes containing gold nanoparticles in the aqueous core. Gold nanoparticles absorb near-infrared light and release the energy as heat that increases the permeability of the liposomal bilayer, thus releasing the contents of the liposome. In this work, we replaced the gold nanoparticles with the clinically approved imaging agent indocyanine green (ICG). The ICG liposomes were stable at storage conditions (4-22 °C) and at body temperature, and fast near-infrared (IR) light-triggered drug release was achieved with optimized phospholipid composition and a 1:50 ICG-to-lipid molar ratio. Encapsulated small molecular calcein and FITC-dextran (up to 20 kDa) were completely released from the liposomes after light exposure for 15 s. Location of ICG in the PEG layer of the liposomes was simulated with molecular dynamics. ICG has important benefits as a light-triggering agent in liposomes: fast content release, improved stability, improved possibility of liposomal size control, regulatory approval to use in humans, and the possibility of imaging the in vivo location of the liposomes based on the fluorescence of ICG. Near-infrared light used as a triggering mechanism has good tissue penetration and safety. Thus, ICG liposomes are an attractive option for light-controlled and efficient delivery of small and large drug molecules. PMID:27097108

  13. Role of Corticotropin-Releasing Factor in Drug Addiction: Potential for Pharmacological Intervention

    PubMed Central

    Logrip, Marian L.; Koob, George F.; Zorrilla, Eric P.

    2012-01-01

    Drug dependence is a chronically relapsing disorder that places an enormous strain on healthcare systems. For treatments to have long-term clinical value, they must address the causes of relapse. Corticotropin-releasing factor (CRF), a neuropeptide central to the stress response, may be one key to solving the relapse cycle. CRF is hypothesized to mediate the elevated anxiety and negative emotional states experienced during the development of dependence. This review summarizes existing data on changes in the CRF system produced by drugs of abuse and the function of CRF receptors in regulating behavioural responses to drugs of abuse, with an emphasis on drug dependence. Drug-induced changes in neuronal excitability throughout the limbic system, as well as the reversal of these neuroadaptations by CRF receptor antagonists, are also addressed. CRF receptor antagonists, by reducing the motivational effects of drug withdrawal and protracted abstinence, are proposed to be novel therapeutic targets for drug abuse and addiction. PMID:21425881

  14. Photothermally activated drug release from liposomes coupled to hollow gold nanoshells

    NASA Astrophysics Data System (ADS)

    Forbes, Natalie; Zasadzinski, Joseph A.

    2011-03-01

    Liposomes show great promise as intravenous drug delivery vehicles, but it is difficult to combine stability in the circulation, extended drug retention and rapid, targeted release at the site of interest. Accessorizing conventional and multicompartment liposomes with photo-activated hollow gold nanoshells (HGN) provides a convenient method to initiate drug release with spatial and temporal control. HGN efficiently absorb near infrared (NIR) light and rapidly convert the absorbed optical energy into heat. Femto- to nano-second NIR light pulses cause the HGNs to rapidly heat, creating large temperature gradients between the HGNs and surrounding fluid. The formation and collapse of unstable vapor bubbles transiently rupture liposome and other bilayer membranes to trigger contents release. Near-complete contents release occurs when the nanoshells are encapsulated within the liposome or tethered to the outer surface of the liposome, with no chemical damage to the contents. Release is achieved by focusing the laser beam at the target, eliminating the need for highly specific targeting ligands or antibodies. Although HGN heating can be intense, the overall energy input is small causing minimal heating of the surroundings. To ensure that drugs are retained within the liposomes until delivery in a physiological environment, we have made novel multicompartment carriers called vesosomes, which consist of an outer lipid bilayer shell that encloses and protects the drug-carrying liposomes. The second bilayer increases the serum half-life of ciprofloxacin from <10 minutes in liposomes to 6 hours in vesosomes and alters the release kinetics. The enhanced drug retention is due to the outer membrane preventing enzymes and proteins in the blood from breaking down the drug-carrying interior compartments.

  15. Controlled drug release from biodegradable thermoresponsive physical hydrogel nanofibers.

    PubMed

    Loh, Xian Jun; Peh, Priscilla; Liao, Susan; Sng, Colin; Li, Jun

    2010-04-19

    Hydrogel nanofiber mats based on thermoresponsive multiblock poly(ester urethane)s comprising poly(ethylene glycol) (PEG), poly(propylene glycol) (PPG), and poly(epsilon-caprolactone) (PCL) segments were fabricated by electrospinning. The hydrogel nanofiber mats were more water absorbent under cold conditions and shrunk when exposed to higher temperatures. The rate of protein release could be controlled by changing the temperature of the nanofiber environment. Cell culture studies on the nanofiber mats were carried out using human dermal fibroblasts, and healthy cell morphology was observed. The adherent viable cells were quantified by MTS after rinsing in excess buffer solution. The results showed that these nanofiber scaffolds supported excellent cell adhesion, comparable with the pure PCL nanofibers. The increased hydrophilicity of these hydrogel nanofiber mats led to a more rapid hydrolytic degradation, compared with the pure PCL nanofiber mats. These hydrogel nanofiber scaffolds could potentially be used as thermoresponsive biodegradable supporting structures for skin tissue engineering applications. PMID:20064568

  16. Oil and drug control the release rate from lyotropic liquid crystals.

    PubMed

    Martiel, Isabelle; Baumann, Nicole; Vallooran, Jijo J; Bergfreund, Jotam; Sagalowicz, Laurent; Mezzenga, Raffaele

    2015-04-28

    The control of the diffusion coefficient by the dimensionality d of the structure appears as a most promising lever to efficiently tune the release rate from lyotropic liquid crystalline (LLC) phases and dispersed particles towards sustained, controlled and targeted release. By using phosphatidylcholine (PC)- and monolinoleine (MLO)-based mesophases with various apolar structural modifiers and water-soluble drugs, we present a comprehensive study of the dimensional structural control of hydrophilic drug release, including 3-d bicontinuous cubic, 2-d lamellar, 1-d hexagonal and 0-d micellar cubic phases in excess water. We investigate how the surfactant, the oil properties and the drug hydrophilicity mitigate or even cancel the effect of structure variation on the drug release rate. Unexpectedly, the observed behavior cannot be fully explained by the thermodynamic partition of the drug into the lipid matrix, which points out to previously overlooked kinetic effects. We therefore interpret our results by discussing the mechanism of structural control of the diffusion rate in terms of drug permeation through the lipid membrane, which includes exchange kinetics. A wide range of implications follow regarding formulation and future developments, both for dispersed LLC delivery systems and topical applications in bulk phase. PMID:25744826

  17. Optimizing the formulation of cyclosporine A electret patch and the controlled release of drug

    NASA Astrophysics Data System (ADS)

    Liu, H. Y.; Wang, P.; Liang, Y. Y.; Guo, X.; Jiang, J.; Cui, L. L.

    2013-03-01

    The polypropylene (PP) film coated with/without aluminum electrode were charged with the gird voltages of -500 V, -1000 V and -2000 V to prepare the electrets and produce electric field for control of drug release. The model drug of cyclosporine A (CsA) was loaded on a patch and ethyl oleate was used as the chemical enhancer in the manufacturing process. The formulation of the CsA drug patch enhanced by chemical was optimized, and the in vitro release behaviours of drug in the patches were studied to explore the enhancing effect of the external electrostatic field on the CsA release from the patch. Besides, the piezoelectric d33 coefficient was also determined to study the polarization of the drug in the patch under the action of the internal electrostatic field of the electret. The results indicate that the electrostatic field produced by the electret could polarize the drug in patch and enhance the release of CsA from the patch, and the effect depended on the electrode coating condition and charging voltage of the electret.

  18. 49 CFR 40.323 - May program participants release drug or alcohol test information in connection with legal...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 1 2011-10-01 2011-10-01 false May program participants release drug or alcohol test information in connection with legal proceedings? 40.323 Section 40.323 Transportation Office of... PROGRAMS Confidentiality and Release of Information § 40.323 May program participants release drug...

  19. Melt-processed polymeric cellular dosage forms for immediate drug release.

    PubMed

    Blaesi, Aron H; Saka, Nannaji

    2015-12-28

    The present immediate-release solid dosage forms, such as the oral tablets and capsules, comprise granular matrices. While effective in releasing the drug rapidly, they are fraught with difficulties inherent in processing particulate matter. By contrast, liquid-based processes would be far more predictable; but the standard cast microstructures are unsuited for immediate-release because they resist fluid percolation and penetration. In this article, we introduce cellular dosage forms that can be readily prepared from polymeric melts by incorporating the nucleation, growth, and coalescence of microscopic gas bubbles in a molding process. We show that the cell topology and formulation of such cellular structures can be engineered to reduce the length-scale of the mass-transfer step, which determines the time of drug release, from as large as the dosage form itself to as small as the thickness of the cell wall. This allows the cellular dosage forms to achieve drug release rates over an order of magnitude faster compared with those of cast matrices, spanning the entire spectrum of immediate-release and beyond. The melt-processed polymeric cellular dosage forms enable predictive design of immediate-release solid dosage forms by tailoring microstructures, and could be manufactured efficiently in a single step. PMID:26519856

  20. Non-polymeric coatings to control drug release from metallic coronary stents

    NASA Astrophysics Data System (ADS)

    Gupta, Celia Edith Macias

    Percutaneous transluminal coronary angiography (PTCA) is a procedure used to re-open narrowed coronary arteries. During PTCA, a coronary stent is expanded inside a diseased vessel and serves as a scaffold to keep the artery open. The major drawback of stenting is restenosis---a re-narrowing of the vessel resulting from the hyperproliferation of smooth muscle cells. Drug eluting stents (DES) reduce the rate of restenosis compared to bare metal stents. Paclitaxel (PAT) is commonly used in DES for its ability to prevent restenosis. However, DES have been associated with thrombosis due to the polymer carrier that controls drug delivery. Therefore, there is a need to change the drug delivery mechanisms to eliminate the need of polymers. The goal of this dissertation is to develop a novel polymer-free drug eluting stent that controls drug release using nanoscale metal coatings. The coating was designed to release PAT as the metal slowly degrades in biological conditions. Once all the Paclitaxel has eluted from the surface, the coating will continue to degrade until the final result is a bare metal stent. The results of this study include a novel non-polymeric drug delivery system using nanoscale coatings that release Paclitaxel at a rate similar to commercial stents, as well as the biocompatibility and efficacy of these coatings. The non-polymeric drug delivery system described here achieved a Paclitaxel release profile equivalent to clinically available Paclitaxel-eluting stents and effectively inhibits smooth muscle cell proliferation, thereby completely eliminating the need for polymers to control drug release from coronary stents.

  1. Inclusion of the poorly water-soluble drug simvastatin in mesocellular foam nanoparticles: drug loading and release properties.

    PubMed

    Zhang, Yanzhuo; Zhang, Jinghai; Jiang, Tongying; Wang, Siling

    2011-05-30

    The purpose of this study was to develop spherical mesocellular foam (MCF) loaded with a poorly water-soluble drug, intended to be orally administered, able to improve the dissolution rate and enhance the drug loading capacity. Spherical MCF with a continuous 3-D pore system was synthesized using Pluronic 123 triblock polymer (P123) as a surfactant coupled with cetyltrimethyl ammonium bromide (CTAB) as a co-surfactant. A model drug, simvastatin (SV), was loaded onto spherical MCF via a procedure involving a combination of adsorption equilibrium and solvent evaporation. The drug release rate and the drug loading efficiency of spherical MCF were compared with those of fibrous SBA-15. Investigations using nitrogen adsorption, scanning electron microscopy (SEM), transmission electron microscopy (TEM), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and HPLC demonstrated the successful incorporation of SV into the MCF host. It was found that spherical MCF has a high drug loading efficiency up to 37.5%, and higher than that of fibrous SBA-15 with a pore diameter of 6.5 nm. It is worth noting that fast release rate of SV was obtained from spherical MCF compared with SBA-15 and pure crystalline SV using enzyme-free simulated intestinal fluid (SIF, pH 6.8). PMID:20674729

  2. Creation of a functional graded nanobiomembrane using a new electrospinning system for drug release control and an in vitro validation of drug release behavior of the coating membrane.

    PubMed

    Park, Chan-Hee; Chung, Min-Young; Unnithan, Afeesh Rajan; Kim, Cheol Sang

    2015-05-01

    Functional graded nanobiomembranes (FGMs) with multiple layers were created by a single process using a novel electrospinning system equipped with a generator and a PCI type motion board as a controller in order to control the drug release rate. By varying physical apparatus-related parameters such as nozzle-to-collector distance via a robot and the collector moving velocity the FGMs were formed. For the membrane base layer, poly-(ε-caprolactone) (PCL) with paclitaxel (PTX) was dissolved in a solvent (dichloromethane, N,N-dimethylformamide) and electrospun. For the top layers, the PCL solution was electrospun according to the distance and FGM system parameters, which can move the collector location at a constant ratio. It was observed that pore size, porosity, and permeability were higher when the membrane was spun at the far distance. The top surface of FGM is more porous, rougher, more permeable, and more hydrophilic so as to be active to the surrounding tissue cells. Meanwhile, the porous inside membrane was as low as the membrane spun at a close distance. Thus it induced a slow drug release due to the internal structure of FGM, which is considered to be very effective for slow drug release as well as bioactivity and bioconductivity. PMID:25746254

  3. Direct encapsulation of water-soluble drug into silica microcapsules for sustained release applications

    SciTech Connect

    Wang Jiexin; Wang Zhihui; Chen Jianfeng Yun, Jimmy

    2008-12-01

    Direct encapsulation of water-soluble drug into silica microcapsules was facilely achieved by a sol-gel process of tetraethoxysilane (TEOS) in W/O emulsion with hydrochloric acid (HCl) aqueous solution containing Tween 80 and drug as well as cyclohexane solution containing Span 80. Two water-soluble drugs of gentamicin sulphate (GS) and salbutamol sulphate (SS) were chosen as model drugs. The characterization of drug encapsulated silica microcapsules by scanning electronic microscopy (SEM), FTIR, thermogravimetry (TG) and N{sub 2} adsorption-desorption analyses indicated that drug was successfully entrapped into silica microcapsules. The as-prepared silica microcapsules were uniform spherical particles with hollow structure, good dispersion and a size of 5-10 {mu}m, and had a specific surface area of about 306 m{sup 2}/g. UV-vis and thermogravimetry (TG) analyses were performed to determine the amount of drug encapsulated in the microcapsules. The BJH pore size distribution (PSD) of silica microcapsules before and after removing drug was examined. In vitro release behavior of drug in simulated body fluid (SBF) revealed that such system exhibited excellent sustained release properties.

  4. Biocompatible drug delivery system for photo-triggered controlled release of 5-Fluorouracil.

    PubMed

    Jin, Qiao; Mitschang, Fabian; Agarwal, Seema

    2011-10-10

    The synthesis of a photo-triggered biocompatible drug delivery system on the basis of coumarin-functionalized block copolymers is reported. The coumarin-functionalized block copolymers poly(ethylene oxide)-b-poly(n-butyl methacrylate-co-4-methyl-[7-(methacryloyl)oxyethyloxy]coumarin)) (PEO-b-P(BMA- co-CMA)) were synthesized via atom transfer radical polymerization (ATRP). The micelle-drug conjugates were made by covalent bonding of anticancer drug 5-fluorouracil (5-FU) to the coumarin under UV irradiation at wavelength >310 nm. These micelle-drug conjugates possessed spherical morphology with diameters of 70 nm from TEM images. In vitro drug release experiments showed the controlled release of anticancer drug 5-FU from the micelle-drug conjugates under UV irradiation (254 nm). These micelle-drug conjugates also showed excellent biocompatibility by the in vitro cytotoxicity experiments. The results suggest that these micelle-drug conjugates could be a promising candidate for the delivery of anticancer agents with low side effects on normal cells and excellent therapeutic efficacy to cancer cells. PMID:21863834

  5. Characterization and in vitro drug release studies of a natural polysaccharide Terminalia catappa gum (Badam gum).

    PubMed

    Meka, Venkata Srikanth; Nali, Sreenivasa Rao; Songa, Ambedkar Sunil; Kolapalli, Venkata Ramana Murthy

    2012-12-01

    The main objective of the present study is the physicochemical characterization of naturally available Terminalia catappa gum (Badam gum [BG]) as a novel pharmaceutical excipient and its suitability in the development of gastroretentive floating drug delivery systems (GRFDDS) to retard the drug for 12 h when the dosage form is exposed to gastrointestinal fluids in the gastric environment. As BG was being explored for the first time for its pharmaceutical application, physicochemical, microbiological, rheological, and stability studies were carried out on this gum. In the present investigation, the physicochemical properties, such as micromeritic, rheological, melting point, moisture content, pH, swelling index, water absorption, and volatile acidity, were evaluated. The gum was characterized by scanning electron microscopy, differential scanning calorimetry (DSC), powder X-ray diffraction studies (PXRD), and Fourier transform infrared spectroscopy (FTIR). Gastroretentive floating tablets of BG were prepared with the model drug propranolol HCl by direct compression methods. The prepared tablets were evaluated for all their physicochemical properties, in vitro buoyancy, in vitro drug release, and rate order kinetics. PBG 04 was selected as an optimized formulation based on its 12-h drug release and good buoyancy characteristics. The optimized formulation was characterized with FTIR, DSC, and PXRD studies, and no interaction between the drug and BG was found. Thus, the study confirmed that BG might be used in the gastroretentive drug delivery system as a release-retarding polymer. PMID:23090110

  6. Charge-Reversal APTES-Modified Mesoporous Silica Nanoparticles with High Drug Loading and Release Controllability.

    PubMed

    Wang, Yifeng; Sun, Yi; Wang, Jine; Yang, Yang; Li, Yulin; Yuan, Yuan; Liu, Changsheng

    2016-07-13

    In this study, we demonstrate a facile strategy (DL-SF) for developing MSN-based nanosystems through drug loading (DL, using doxorubicin as a model drug) followed by surface functionalization (SF) of mesoporous silica nanoparticles (MSNs) via aqueous (3-aminopropyl)triethoxysilane (APTES) silylation. For comparison, a reverse functionalization process (i.e., SF-DL) was also studied. The pre-DL process allows for an efficient encapsulation (encapsulation efficiency of ∼75%) of an anticancer drug [doxorubicin (DOX)] inside MSNs, and post-SF allows in situ formation of an APTES outer layer to restrict DOX leakage under physiological conditions. This method makes it possible to tune the DOX release rate by increasing the APTES decoration density through variation of the APTES concentration. However, the SF-DL approach results in a rapid decrease in drug loading capacity with an increase in APTES concentration because of the formation of the APTES outer layer hampers the inner permeability of the DOX drug, resulting in a burst release similar to that of undecorated MSNs. The resulting DOX-loaded DL-SF MSNs present a slightly negatively charged surface under physiological conditions and become positively charged in and extracellular microenvironment of solid tumor due to the protonation effect under acidic conditions. These merits aid their maintenance of long-term stability in blood circulation, high cellular uptake by a kind of skin carcinoma cells, and an enhanced intracellular drug release behavior, showing their potential in the delivery of many drugs beyond anticancer chemotherapeutics. PMID:27314423

  7. Diffusion and Controlled Localized Drug Release from an Injectable Solid Self-Assembling Peptide Hydrogel

    NASA Astrophysics Data System (ADS)

    Sun, Jessie E. P.; Stewart, Brandon; Langhans, Sigrid; Stewart, Joel P.; Pochan, Darrin J.

    2014-03-01

    We use an injectable solid peptide hydrogel (first assembled into a solid hydrogel, can shear-thin flow and immediately reheal on cessation of shear) as a drug delivery vehicle for sustained and active drug release. The triggered intramolecular peptide folding into a beta-hairpin leads to intermolecular assmebly of the peptides into the entangled and branched nanofibrillar hydrogel network responsible for its advantageous rheological properties. The hydrogel is used to encapsulate a highly effective chemotherapeutic, vincristine, with hydrophobic behavior. We show that we are able to constantly maintain drug release in low but still potent concentrations after the shear-thinning injection process. Similarly, the mechanical and morphoogical properties of the gels remains identical after injection. Characterization of the hydrogel construct is through tritiated vincristine release, TEM, confocal microscopy, and in vitro methods.

  8. Synthesis, characterization, and controllable drug release of pH-sensitive hybrid magnetic nanoparticles

    NASA Astrophysics Data System (ADS)

    Zhou, Lilin; Yuan, Jinying; Yuan, Weizhong; Sui, Xiaofeng; Wu, Sizhu; Li, Zhaolong; Shen, Dezhong

    2009-09-01

    The synthesis of magnetite nanoparticles coated with pH-sensitive poly((2-dimethylamino) ethyl methacrylate) (PDMAEMA) via atom transfer radical polymerization (ATRP) for use as novel potential carriers for targeted drug delivery and controllable release is reported. The organic/inorganic hybrid nanoparticles were obtained with a narrow molecular weight distribution. The pH-sensitivity of the nanoparticles was investigated by the measurement of the pH dependence of hydrodynamic radius and the superparamagnetism was illustrated by vibrating sample magnetometer (VSM). The behavior of model drug phenolphthalein released from the nanoparticles indicated that the rate of drug release could be effectively controlled by altering the pH values of the environment.

  9. Fabrication of autofluorescent porous silica nanoparticles for redox-responsive drug release.

    PubMed

    Cao, Na; Zhao, Yanbao; Sang, Bin; Wang, Zhihua; Cao, Liuqin; Sun, Lei; Zou, Xueyan

    2016-12-01

    Porous silica nanoparticles were prepared by emulsion-condensation route. The silica nanoparticles with diameter of 50nm have both accessible center-radial large pore channels (19.9nm) and small pore size of 3.5nm. The hierarchical porous structure endows them large pore volume for loading drugs and sustained release property. The silica nanoparticles were further modified with glucose-oxidized glutathione. The formulated Schiff base and disulfide bonds render the silica nanoparticles auto-fluorescent and redox-responsive properties. The cleavage of disulfide bonds caused by reactive thiols facilitates aminomethylbenzoic acid (AMA) release. The release of drug leads to the loss of fluorescence, which would be used to monitor the drug delivery and carrier distribution. PMID:27612720

  10. Polyelectrolyte/carbon nanotube composite microcapsules and drug release triggered by laser irradiation

    NASA Astrophysics Data System (ADS)

    Saito, Haruyuki; Kato, Noritaka

    2016-03-01

    The fabrication of stimuli-responsive capsules is one of the hot topics in the research field of drug delivery systems. Near-infrared (NIR) light is one of the promising stimuli, because of its high transparency to biological tissues, and NIR-responsive capsules have been fabricated using various NIR-adsorbing materials. Here, we employed single-walled carbon nanotubes (SWCNTs) as the NIR-adsorbing material, and microcapsules containing SWCNTs were fabricated by a combination of the layer-by-layer and template-assisted methods. The anti-cancer drug was loaded into the capsules, and the release rates in the dark and under NIR laser irradiation were compared. Distinct release was confirmed in the latter case, whereas almost no release was detected in the former case, indicating that the SWCNT molecule is a suitable light absorber for use with optically addressable drug carriers.

  11. Continuous wide-field characterization of drug release from skin substitute using off-axis interferometry.

    PubMed

    Gabai, Haniel; Baranes-Zeevi, Maya; Zilberman, Meital; Shaked, Natan T

    2013-08-15

    We achieved continuous, noncontact wide-field imaging and characterization of drug release from a polymeric device in vitro by uniquely using off-axis interferometric imaging. Unlike the current gold-standard methods in this field, which are usually based on chromatography and spectroscopy, our method requires no user intervention during the experiment and involves less lab consumable instruments. Using a simplified interferometric imaging system, we experimentally demonstrate the characterization of anesthetic drug release (Bupivacaine) from a soy-based protein matrix, which is used as a skin substitute for wound dressing. Our results demonstrate the potential of interferometric imaging as an inexpensive and easy-to-use alternative for characterization of drug release in vitro. PMID:24104636

  12. Sucrose esters with various hydrophilic-lipophilic properties: novel controlled release agents for oral drug delivery matrix tablets prepared by direct compaction.

    PubMed

    Chansanroj, K; Betz, G

    2010-08-01

    Sucrose esters (SE) are esters of sucrose and fatty acids with various hydrophilic-lipophilic properties which have attracted interest from being used in pharmaceutical applications. This study aimed to gain insight into the use of SE as controlled release agents for direct compacted matrix tablets. The study focused on the effect of hydrophilic-lipophilic properties on tableting properties and drug release. Sucrose stearate with hydrophilic-lipophilic balance (HLB) values ranging from 0 to 16 was systematically tested. Tablet formulations contained SE, metoprolol tartrate as a highly soluble model drug and dibasic calcium phosphate dihydrate as a tablet formulation filler in the ratio 1:1:2. The compaction behaviour of matrix tablets was compared with the compacts of individual starting materials as reference. SE incorporation improved the plasticity, compressibility and lubricating property of powder mixtures. The hydrophilic-lipophilic properties of SE affected tableting properties, drug release rate and release mechanism. Increasing hydrophilicity corresponding to the increased monoesters in SE composition increased the relative porosity, elastic recovery and tensile strength of the tablets due to the increased hydrogen bonding between the monoesters. This also facilitated the swelling behaviour of SE, which sustained the drug release rate. A sustained release effect prevailed in tablets containing SE with HLB values of 3-16. The ability to improve the tableting properties as well as sustain the drug release rate of the highly soluble model drug via gelation of SE highlights SE as promising controlled release regulators for direct compacted matrix tablets comprising drugs with various solubilities according to the Biopharmaceutics Classification System. PMID:20132913

  13. Guide to Children Affected by Parental Drug Abuse

    ERIC Educational Resources Information Center

    Davies, Leah

    2010-01-01

    A conservative estimate is that one in six children in school today has a parent dependent on or addicted to alcohol or other drugs. This places these students at high risk for social and emotional problems, as well as for school failure, drug use, and delinquency. Schools, however, are a logical place to reach them. Identifying children of those…

  14. Huperzine A-phospholipid complex-loaded biodegradable thermosensitive polymer gel for controlled drug release.

    PubMed

    Cai, Xiaoqing; Luan, Yuxia; Jiang, Yue; Song, Aixin; Shao, Wei; Li, Zhonghao; Zhao, Zhongxi

    2012-08-20

    The huperzine A-phospholipid complex loaded biodegradable thermosensitive PLGA-PEG-PLGA polymer gel was studied as injectable implant system for controlled release of huperzine-A (HA). First, HA molecules were successfully incorporated into the soybean phosphatidylcholine (SP) molecules to form the huperzine-A-soybean phosphatidylcholine complexes (HA-SPC), which was proved by FT-IR, DSC, XRD, solubility study, TEM, etc. The results indicated that hydrogen bonds and electrostatic interaction between HA and SP molecules play an important role in the formation of HA-SPC. Secondly, the HA-SPC was loaded into biodegradable PLGA-PEG-PLGA thermosensitive gel as injectable implant material to control the release of HA. The in vitro and in vivo drug release behaviors of the prepared products were studied. The in vitro release studies demonstrated that the HA-SPC-loaded gel significantly reduced the initial burst of drug release and extended the release period to about 2 weeks. The in vivo pharmacokinetics study of HA-SPC-loaded gel in rabbits showed that plasma concentration of HA (2.54-0.15ng/mL) was detected for nearly 2 weeks from delivery systems upon single subcutaneous injection. What's more, the in vitro release pattern correlated well with the in vivo pharmacokinetics profile. The present study indicates that HA-SPC loaded PLGA-PEG-PLGA thermal gel may be an attractive candidate vehicle for controlled HA release. PMID:22583846

  15. Influence of nootropic drugs on the age-dependent potassium-coupling of transmitter release.

    PubMed

    Wustmann, C; Blaschke, M; Rudolph, E; Fischer, H D; Schmidt, J

    1990-01-01

    The potassium-induced dopamine release from rat striatum slices shows an age-dependent decline comparable to observations after hypoxia. Pretreatment of aged animals with antihypoxically active nootropic drugs for three weeks results in an improvement of the impaired transmitter release. Simultaneously the slope of the stimulus-release relation is increased and an age-related 50% decrease of the high affinity Ca(++)-ATPase activity (brain P2 fraction) is partially compensated. Like the antihypoxic effect, the effectiveness of nootropic drugs regarding age-dependent changes of neuronal functions probably will consist, above all, in vascular influences of the microcirculation, repair of phospholipids damaged by free radical triggered peroxidation and improvement of stimulus-release coupling. PMID:2149265

  16. Intelligent Janus nanoparticles for intracellular real-time monitoring of dual drug release

    NASA Astrophysics Data System (ADS)

    Cao, Han; Yang, Yuhong; Chen, Xin; Shao, Zhengzhong

    2016-03-01

    Stimuli-responsive nanomaterials have been receiving much attention as drug delivery carriers, however understanding of multi-drug release from the carriers for efficient therapeutics is highly challenging. Here, we report a novel nanosystem, Janus particle Dox-CMR-MS/Au-6MP (Dox: doxorubicin, CMR: 7-hydroxycoumarin-3-carboxylate, MS: mesoporous silica, Au: gold, 6MP: 6-mercaptopurine) with opposing MS and Au faces, which can monitor intracellular dual-drug (Dox and 6MP) controlled release in real time based on fluorescence resonance energy transfer (FRET) and surface-enhanced Raman scattering (SERS). The FRET acceptor Dox is attached to CMR (as a FRET donor) conjugated MS with a pH-responsive linker hydrazone, and 6MP is conjugated to the Au surface through the gold-thiol interaction. As the Janus nanoparticle enters into tumor cells, the breakage of the hydrazone bond in an acidic environment and the substitution of glutathione (GSH) overexpressed in cancer cells give rise to the release of Dox and 6MP, respectively. Thus, the change of the CMR fluorescence signal and the SERS decrease of 6MP can be used to monitor the dual-drug release within living cells in real time. In addition, this work demonstrates the enhanced anticancer effect of the designed dual-drug loaded nanosystem. Therefore, the current study may provide new perspectives for the real-time study of intelligent multi-drug delivery and release, as well as cellular responses to drug treatment.Stimuli-responsive nanomaterials have been receiving much attention as drug delivery carriers, however understanding of multi-drug release from the carriers for efficient therapeutics is highly challenging. Here, we report a novel nanosystem, Janus particle Dox-CMR-MS/Au-6MP (Dox: doxorubicin, CMR: 7-hydroxycoumarin-3-carboxylate, MS: mesoporous silica, Au: gold, 6MP: 6-mercaptopurine) with opposing MS and Au faces, which can monitor intracellular dual-drug (Dox and 6MP) controlled release in real time based on

  17. Development of sustained and dual drug release co-extrusion formulations for individual dosing.

    PubMed

    Laukamp, Eva Julia; Vynckier, An-Katrien; Voorspoels, Jody; Thommes, Markus; Breitkreutz, Joerg

    2015-01-01

    In personalized medicine and patient-centered medical treatment individual dosing of medicines is crucial. The Solid Dosage Pen (SDP) allows for an individual dosing of solid drug carriers by cutting them into tablet-like slices. The aim of the present study was the development of sustained release and dual release formulations with carbamazepine (CBZ) via hot-melt co-extrusion for the use in the SDP. The selection of appropriate coat- and core-formulations was performed by adapting the mechanical properties (like tensile strength and E-modulus) for example. By using different excipients (polyethyleneglycols, poloxamers, white wax, stearic acid, and carnauba wax) and drug loadings (30-50%) tailored dissolution kinetics was achieved showing cube root or zero order release mechanisms. Besides a biphasic drug release, the dose-dependent dissolution characteristics of sustained release formulations were minimized by a co-extruded wax-coated formulation. The dissolution profiles of the co-extrudates were confirmed during short term stability study (six months at 21.0 ± 0.2 °C, 45%r.h.). Due to a good layer adhesion of core and coat and adequate mechanical properties (maximum cutting force of 35.8 ± 2.0 N and 26.4 ± 2.8 N and E-modulus of 118.1 ± 8.4 and 33.9 ± 4.5 MPa for the dual drug release and the wax-coated co-extrudates, respectively) cutting off doses via the SDP was precise. While differences of the process parameters (like the barrel temperature) between the core- and the coat-layer resulted in unsatisfying content uniformities for the wax-coated co-extrudates, the content uniformity of the dual drug release co-extrudates was found to be in compliance with pharmacopoeial specification. PMID:25555454

  18. Development of sustained release gastroretentive drug delivery system for ofloxacin: in vitro and in vivo evaluation.

    PubMed

    Chavanpatil, Mahesh; Jain, Paras; Chaudhari, Sachin; Shear, Rajesh; Vavia, Pradeep

    2005-11-01

    Sustained release (SR)-gastroretentive dosage forms (GRDF) enable prolonged and continuous input of the drug to the upper parts of the gastrointestinal (GI) tract and improve the bioavailability of medications that are characterized by a narrow absorption window. A new strategy is proposed for the development of gastroretentive dosage forms for ofloxacin preferably once daily. The design of the delivery system was based on the sustained release formulation, with floating and swelling features in order to prolong the gastric retention time of the drug delivery systems. Different polymers, such as psyllium husk, HPMC K100M, crospovidone and its combinations were tried in order to get the desired sustained release profile over a period of 24 h. Various formulations were evaluated for buoyancy lag time, duration of buoyancy, dimensional stability, drug content and in vitro drug release profile. It was found that dimensional stability of the formulation increases with the increasing psyllium husk concentration. It was also found that in vitro drug release rate increased with increasing amount of crospovidone due to the increased water uptake, and hence increased driving force for drug release. The optimized formulation was subjected to stability studies at different temperature and humidity conditions as per ICH guidelines. In vivo studies were carried out for the optimized formulation in 24 healthy human volunteers and the pharmacokinetic parameters of developed formulations were compared with the marketed once daily (Zanocin) formulation. Based on the in vivo performance in a parallel study design in healthy subjects, the developed formulation shows promise to be bioequivalent to the marketed product (Zanocin). The percent relative bioavailability of developed formulation was found to be 97.55%. PMID:16198522

  19. Sub-100 nm gold nanoparticle vesicles as a drug delivery carrier enabling rapid drug release upon light irradiation.

    PubMed

    Niikura, Kenichi; Iyo, Naoki; Matsuo, Yasutaka; Mitomo, Hideyuki; Ijiro, Kuniharu

    2013-05-01

    Previously, we reported gold nanoparticles coated with semifluorinated ligands self-assembled into gold nanoparticle vesicles (AuNVs) with a sub-100 nm diameter in tetrahydrofuran (THF). (1) Although this size is potentially useful for in vivo use, the biomedical applications of AuNVs were limited, as the vesicular structure collapsed in water. In this paper, we demonstrate that the AuNVs can be dispersed in water by cross-linking each gold nanoparticle with thiol-terminated PEG so that the cross-linked vesicles can work as a drug delivery carrier enabling light-triggered release. Rhodamine dyes or anticancer drugs were encapsulated within the cross-linked vesicles by heating to 62.5 °C. At this temperature, the gaps between nanoparticles open, as confirmed by a blue shift in the plasmon peak and the more efficient encapsulation than that observed at room temperature. The cross-linked AuNVs released encapsulated drugs upon short-term laser irradiation (5 min, 532 nm) by again opening the nanogaps between each nanoparticle in the vesicle. On the contrary, when heating the solution to 70 °C, the release speed of encapsulated dyes was much lower (more than 2 h) than that triggered by laser irradiation, indicating that cross-linked AuNVs are highly responsive to light. The vesicles were efficiently internalized into cells compared to discrete gold nanoparticles and released anticancer drugs upon laser irradiation in cells. These results indicate that cross-linked AuNVs, sub-100 nm in size, could be a new type of light-responsive drug delivery carrier applicable to the biomedical field. PMID:23566248

  20. Photoactive Fluoropolymer Surfaces that Release Sensitizer Drug Molecules

    PubMed Central

    Ghosh, Goutam; Minnis, Mihaela; Ghogare, Ashwini A.; Abramova, Inna; Cengel, Keith; Busch, Theresa M.; Greer, Alexander

    2015-01-01

    We describe a physical-organic study of two fluoropolymers bearing a photoreleasable PEGylated photosensitizer which generates 1O2(1Δg) [chlorin e6 methoxy tri(ethylene glycol) triester]. The surfaces are Teflon/polyvinylalcohol (PVA) nanocomposite and fluorinated silica. The relative efficiency of these surfaces to photorelease the PEGylated sensitizer [shown previously to be phototoxic to ovarian cancer cells (Kimani, S. et al J. Org. Chem 2012, 77, 10638)] was slightly higher for the nanocomposite. In the presence of red light and O2, 1O2 is formed, which cleaves an ethene linkage to liberate the sensitizer in 68–92% yields. The fluoropolymers were designed to deal with multiple problems. Namely, their success relied not only high O2 solubility and drug repellency, but that the C−F bonds physically quench little 1O2 for its productive use away from the surface. The results obtained here indicate that Teflon-like surfaces have potential uses of delivering sensitizer and singlet oxygen for applications in tissue repair and photodynamic therapy (PDT). PMID:25686407

  1. Photoactive fluoropolymer surfaces that release sensitizer drug molecules.

    PubMed

    Ghosh, Goutam; Minnis, Mihaela; Ghogare, Ashwini A; Abramova, Inna; Cengel, Keith A; Busch, Theresa M; Greer, Alexander

    2015-03-12

    We describe a physical-organic study of two fluoropolymers bearing a photoreleasable PEGylated photosensitizer that generates (1)O2((1)Δg) [chlorin e6 methoxy tri(ethylene glycol) triester]. The surfaces are Teflon/poly(vinyl alcohol) (PVA) nanocomposite and fluorinated silica. The relative efficiency of these surfaces to photorelease the PEGylated sensitizer [shown previously to be phototoxic to ovarian cancer cells (Kimani, S. et al. J. Org. Chem 2012, 77, 10638)] was slightly higher for the nanocomposite. In the presence of red light and O2, (1)O2 is formed, which cleaves an ethene linkage to liberate the sensitizer in 68-92% yield. The fluoropolymers were designed to deal with multiple problems. Namely, their success relied not only on high O2 solubility and drug repellency but also on the C-F bonds, which physically quench little (1)O2, for singlet oxygen's productive use away from the surface. The results obtained here indicate that Teflon-like surfaces have potential uses in delivering sensitizer and singlet oxygen for applications in tissue repair and photodynamic therapy (PDT). PMID:25686407

  2. Kinetic models for the release of the anticancer drug doxorubicin from biodegradable polylactide/metal oxide-based hybrids.

    PubMed

    Mhlanga, Nikiwe; Ray, Suprakas Sinha

    2015-01-01

    For decades, studies on drug-release kinetics have been an important topic in the field of drug delivery because they provide important insights into the mechanism of drug release from carriers. In this work, polylactide (PLA), doxorubicin (DOX), and metal oxide (MO) (titanium dioxide, magnetic iron oxide, and zinc oxide) spheres were synthesised using the solvent-evaporation technique and were tested for sustained drug release. The efficacy of a dosage system is determined by its ability to deliver the drug at a sustained rate, afford an increased plasma half-life, a minimum exposure of toxic drugs to healthy cells and a high drug pay load. Mathematical models were used to elucidate the release mechanism of the drug from the spheres. The release fitted a zero-order model with a correlation coefficient in the range of 0.9878-0.9891 and the release mechanism followed an anomalous release, meaning drug release was afforded through both diffusion and the dissolution of PLA. Therefore, PLA/DOX/MO released the same amount of drug per unit time. Consequently, the potential for PLA use as a carrier was ascertained. PMID:25450549

  3. Coatings of Eudragit(®) RL and L-55 Blends: Investigations on the Drug Release Mechanism.

    PubMed

    Wulff, Robert; Leopold, Claudia S

    2016-04-01

    In a previous study, generally lower drug release rates from RL:L55 blend coated pellets in neutral/basic release media than in acidic release media were reported. The aim of this study was to obtain information on the drug release mechanism of solid dosage forms coated with blends of Eudragit(®) RL (RL) and Eudragit(®) L-55 (L55). Swelling experiments with free films were analyzed spectroscopically and gravimetrically to identify the physicochemical cause for this release behavior. With Raman spectroscopy, the swelling of copolymer films could be monitored. IR spectroscopic investigations on RL:L55 blends immersed in media at pH 6.8 confirmed the formation of interpolyelectrolyte complexes (IPECs) that were not detectable after swelling in hydrochloric acid pH 1.2. Further investigations revealed that these IPECs decreased the extent of ion exchange between the quaternary ammonium groups of RL and the swelling media. This is presumably the reason for the previously reported decreased drug permeability of RL:L55 coatings in neutral/basic media as ion exchange is the determining factor in drug release from RL coated dosage forms. Gravimetric erosion studies confirmed that L55 was not leached out of the film blends during swelling in phosphate buffer pH 6.8. In contrast to all other investigated films, the 4:1 (RL:L55) blend showed an extensive swelling within 24 h at pH 6.8 which explains the reported sigmoidal release behavior of 4:1 blend coated pellets. These results help to understand the release behavior of RL:L55 blend coated solid dosage forms. PMID:26265188

  4. A luminescent ruthenium(II) complex for light-triggered drug release and live cell imaging.

    PubMed

    Karaoun, Nora; Renfrew, Anna K

    2015-09-25

    We report a novel ruthenium(II) complex for selective release of the imidazole-based drug econazole. While the complex is highly stable and luminescent in the dark, irradiation with green light induces release of one of the econazole ligands, which is accompanied by a turn-off luminescence response and up to a 34-fold increase in cytotoxicity towards tumour cells. PMID:26248575

  5. Effect of calcium ions on the gelling and drug release characteristics of xanthan matrix tablets.

    PubMed

    Baumgartner, Sasa; Pavli, Matej; Kristl, Julijana

    2008-06-01

    Xanthan is a well-known biopolymer. It is an anionic polysaccharide, whose primary structure depends on the bacterial strain and fermentation conditions. Xanthan was extensively studied in combination with galactomannans, and over 90 patents cover the technology of this preparation. Our aim was to investigate the relation between the physical properties of a xanthan matrix in the absence or presence of calcium ions and its influence on the release of pentoxifylline. The release of pentoxifylline from xanthan tablets in purified water was shown to be very slow and governed by the process of polymer relaxation. The presence of calcium ions significantly increased the drug release, changing the release mechanism into a more diffusion controlled one. Xanthan matrices showed substantially faster and more extensive swelling in water than in the presence of Ca2+ ions. Surprisingly, negative correlation between drug release and degree of swelling was obtained for xanthan: the higher the swelling, the slower the drug release. Higher ionic strength led to lower erosion of xanthan tablets, and the gel layers formed were more rigid and of firmer texture, as shown by rheological experiments and textural profiling. The results indicate that the presence of Ca2+ ions in the solution or in matrices does not cause crosslinking of xanthan polymers, but causes charge screening of ionized groups on the trisaccharide side chains of xanthan, leading to lower inter-molecular repulsion and changing water arrangement. The understanding of the parameters influencing drug release leads to the conclusion that xanthan is suitable for controlled release formulations, especially with the incorporation of certain small counterions. PMID:18248802

  6. Functionalized mesoporous materials for adsorption and release of different drug molecules: A comparative study

    SciTech Connect

    Wang Gang; Otuonye, Amy N.; Blair, Elizabeth A.; Denton, Kelley; Tao Zhimin; Asefa, Tewodros

    2009-07-15

    The adsorption capacity and release properties of mesoporous materials for drug molecules can be improved by functionalizing their surfaces with judiciously chosen organic groups. Functionalized ordered mesoporous materials containing various types of organic groups via a co-condensation synthetic method from 15% organosilane and by post-grafting organosilanes onto a pre-made mesoporous silica were synthesized. Comparative studies of their adsorption and release properties for various model drug molecules were then conducted. Functional groups including 3-aminopropyl, 3-mercaptopropyl, vinyl, and secondary amine groups were used to functionalize the mesoporous materials while rhodamine 6G and ibuprofen were utilized to investigate the materials' relative adsorption and release properties. The self-assembly of the mesoporous materials was carried out in the presence of cetyltrimethylammonium bromide (CTAB) surfactant, which produced MCM-41 type materials with pore diameters of {approx}2.7-3.3 nm and moderate to high surface areas up to {approx}1000 m{sup 2}/g. The different functional groups introduced into the materials dictated their adsorption capacity and release properties. While mercaptopropyl and vinyl functionalized samples showed high adsorption capacity for rhodamine 6G, amine functionalized samples exhibited higher adsorption capacity for ibuprofen. While the diffusional release of ibuprofen was fitted on the Fickian diffusion model, the release of rhodamine 6G followed Super Case-II transport model. - Graphical abstract: The adsorption capacity and release properties of mesoporous materials for various drug molecules are tuned by functionalizing the surfaces of the materials with judiciously chosen organic groups. This work reports comparative studies of the adsorption and release properties of functionalized ordered mesoporous materials containing different hydrophobic and hydrophilic groups that are synthesized via a co-condensation and post

  7. Chitosan derivatives as effective nanocarriers for ocular release of timolol drug.

    PubMed

    Siafaka, Panoraia I; Titopoulou, Alexandra; Koukaras, Emmanuel N; Kostoglou, Margaritis; Koutris, Efthimios; Karavas, Evangelos; Bikiaris, Dimitrios N

    2015-11-10

    The aim of the present study was to evaluate the effectiveness of neat chitosan (CS) and its derivatives with succinic anhydride (CSUC) and 2-carboxybenzaldehyde (CBCS) as appropriate nanocarriers for ocular release of timolol maleate (Tim). Drug nanoencapsulation was performed via ionic crosslinking gelation of the used carriers and sodium tripolyphosphate (TPP). Nanoparticles with size ranged from about 190 to 525 nm were prepared and it was found that the formed size was directly depended on the used carrier and their ratios with TPP. For CS derivatives it was found that as the amount of TPP increased, the particle size increased too, while both derivatives proceeded to nanoparticles with smaller size than that of neat CS. The interactions between carriers and TPP were studied theoretically using all-electron calculations within the framework of density functional theory (DFT). In most of nanoparticles formulations, Tim was entrapped in amorphous form, while the drug entrapment efficiency was higher in CBCS derivative.It was indicated that Tim release rate depended mainly on the used carrier, particle size of prepared nanocarriers and drug loading. From the theoretical release data analysis, it was found that the Tim release was a stagewise procedure with drug diffusion being the dominant release mechanism for each stage. PMID:26341322

  8. Mimicking Biological Delivery Through Feedback-Controlled Drug Release Systems Based on Molecular Imprinting

    PubMed Central

    Kryscio, David R.; Peppas, Nicholas A.

    2015-01-01

    Intelligent drug delivery systems (DDS) are able to rapidly detect a biological event and respond appropriately by releasing a therapeutic agent; thus, they are advantageous over their conventional counterparts. Molecular imprinting is a promising area that generates a polymeric network which can selectively recognize a desired analyte. This field has been studied for a variety of applications over a long period of time, but only recently has it been investigated for biomedical and pharmaceutical applications. Recent work in the area of molecularly imprinted polymers in drug delivery highlights the potential of these recognitive networks as environmentally responsive DDS that can ultimately lead to feedback controlled recognitive release systems. PMID:26500352

  9. Phosphorylated curdlan microgels. Preparation, characterization, and in vitro drug release studies.

    PubMed

    Popescu, Irina; Pelin, Irina M; Butnaru, Maria; Fundueanu, Gheorghe; Suflet, Dana M

    2013-05-15

    Curdlan derivative with anionic phosphate groups was used for the first time to obtain hydrogel microspheres. The chemical cross-linking of the phosphorylated curdlan was performed with epichlorohydrin using the water-in-oil inverse emulsion technique. The optical and scanning electron microscopies were used to analyze the morphology of the microgels, whereas the FTIR spectroscopy was used to investigate their chemical structure. The main characteristics such as the swelling degree, the exchange capacity, and the thermal resistance were also studied. These new anionic microgels could be used as potential carriers for controlled release of opposite charged drugs retained through electrostatic forces. Diphenhydramine, a cationic model drug, was used to investigate the loading and the release processes in various pH media simulating physiological fluids. Several mathematical models were applied to evaluate the drug transport processes and to calculate the drug diffusion coefficients. The synthesized microspheres presented an excellent biocompatibility. PMID:23544647

  10. Bovine serum albumin nanoparticles as controlled release carrier for local drug delivery to the inner ear

    PubMed Central

    2014-01-01

    Nanoparticles have attracted increasing attention for local drug delivery to the inner ear recently. Bovine serum albumin (BSA) nanoparticles were prepared by desolvation method followed by glutaraldehyde fixation or heat denaturation. The nanoparticles were spherical in shape with an average diameter of 492 nm. The heat-denatured nanoparticles had good cytocompatibility. The nanoparticles could adhere on and penetrate through the round window membrane of guinea pigs. The nanoparticles were analyzed as drug carriers to investigate the loading capacity and release behaviors. Rhodamine B was used as a model drug in this paper. Rhodamine B-loaded nanoparticles showed a controlled release profile and could be deposited on the osseous spiral lamina. We considered that the bovine serum albumin nanoparticles may have potential applications in the field of local drug delivery in the treatment of inner ear disorders. PMID:25114637

  11. Anticancer drug release from poly(N-isopropylacrylamide/itaconic acid) copolymeric hydrogels

    NASA Astrophysics Data System (ADS)

    Taşdelen, B.; Kayaman-Apohan, N.; Güven, O.; Baysal, B. M.

    2005-08-01

    The drug uptake and release of anticancer drug from N-isopropylacrylamide/itaconic acid copolymeric hydrogels containing 0-3 mol% of itaconic acid irradiated at 48 kGy have been investigated. 5-Fluorouracil (5-FU) is used as a model anticancer drug. The effect of 5-FU solution on swelling characteristics of PNIPAAm and P(NIPAAm/IA) copolymeric hydrogels have also been studied. The percent swelling, equilibrium swelling, equilibrium water/5-FU content and diffusion constant values are evaluated for poly(N-isopropylacrylamide) (PNIPAAm) and poly(N-isopropylacrylamide/itaconic) (P(NIPAAm/IA)) hydrogels at 130 ppm of 5-FU solution at room temperature. Diffusion of 5-FU solution into the hydrogels has been found to be the non-Fickian type. Finally, the kinetics of drug release from the hydrogels are examined.

  12. Bovine serum albumin nanoparticles as controlled release carrier for local drug delivery to the inner ear

    NASA Astrophysics Data System (ADS)

    Yu, Zhan; Yu, Min; Zhang, Zhibao; Hong, Ge; Xiong, Qingqing

    2014-07-01

    Nanoparticles have attracted increasing attention for local drug delivery to the inner ear recently. Bovine serum albumin (BSA) nanoparticles were prepared by desolvation method followed by glutaraldehyde fixation or heat denaturation. The nanoparticles were spherical in shape with an average diameter of 492 nm. The heat-denatured nanoparticles had good cytocompatibility. The nanoparticles could adhere on and penetrate through the round window membrane of guinea pigs. The nanoparticles were analyzed as drug carriers to investigate the loading capacity and release behaviors. Rhodamine B was used as a model drug in this paper. Rhodamine B-loaded nanoparticles showed a controlled release profile and could be deposited on the osseous spiral lamina. We considered that the bovine serum albumin nanoparticles may have potential applications in the field of local drug delivery in the treatment of inner ear disorders.

  13. Construction of a novel pH-sensitive drug release system from mesoporous silica tablets coated with Eudragit

    NASA Astrophysics Data System (ADS)

    Xu, Yingpu; Qu, Fengyu; Wang, Yu; Lin, Huiming; Wu, Xiang; Jin, Yingxue

    2011-03-01

    A novel pH-sensitive drug release system has been established by coating Eudragit (Eud) on drug-loaded mesoporous silica (MS) tablets. The release rate of ibuprofen (IBU) from the MS was retarded by coating with Eudragit S-100, and the higher retardation was due to the increase of coating concentration and the coating layers. The target position of the release depended on the pH of the release medium, which was confirmed by the drug release from IBU/MS/Eud increasing rapidly with the change of medium pH from 1.2 to 7.4. This drug delivery system could prohibit irritant drug from leaking in the stomach and make it only release in the intestine. The loaded and unloaded drug samples were characterized by powder X-ray diffraction (XRD), Fourier transform infrared spectrometer (FTIR), N 2 adsorption/desorption, scanning electron microscopy (SEM), and transmission electron microscopy (TEM).

  14. Low temperature direct 3D printed bioceramics and biocomposites as drug release matrices.

    PubMed

    Gbureck, Uwe; Vorndran, Elke; Müller, Frank A; Barralet, Jake E

    2007-09-26

    The aim of this study was to investigate the adsorption and desorption kinetics of antibiotics to microporous bioceramics fabricated by a novel low temperature 3D powder direct printing process. The adsorption of vancomycin, ofloxacin and tetracycline onto hydroxyapatite, brushite and monetite showed a linear correlation with the drug concentration in the immersion solution, whereas a non-linear relationship was found between the immersion time and the amount of adsorbed drug. Differences in the total amount of adsorbed drugs were correlated to the specific surface areas of the matrices, which varied between 2.4-13.1 m(2)/g. Normalised drug loadings were found to be in the range of 1.5-1.8 mg/m(2) for vancomycin and ofloxacin, whereas higher loads of up to 5-7 mg/m(2) were obtained for tetracycline. Vancomycin and ofloxacin were rapidly released into PBS buffer within 1-2 days, while tetracycline showed a much slower release rate of approximately 25% after 5 days of immersion. Additional polymer impregnation of the drug loaded matrix with PLA/PGA polymer solutions enabled the release kinetics to be delayed such that sustained release was achieved in polymer ceramic biocomposites. PMID:17655962

  15. Fabrication and evaluation of the novel reduction-sensitive starch nanoparticles for controlled drug release.

    PubMed

    Yang, Jinlong; Huang, Yinjuan; Gao, Chunmei; Liu, Mingzhu; Zhang, Xinjie

    2014-03-01

    A novel type of reduction-sensitive starch nanoparticles was prepared via the reversed-phase microemulsion method by using crosslinker, N,N-bisacryloylcystamine (BAC) with the disulfide linkages, which was specifically cleaved by dithiothreitol (DTT). Starch nanoparticles had a spherical morphology with a small size of 40 nm in the optimal condition. The influences of process parameters (starch amount, surfactant amount and oil/water (O/W) ratio) on the size of starch nanoparticles were studied by dynamic light scattering (DLS). BAC crosslinked starch nanoparticles were degraded into oligomers with the reducing agent of DTT due to the cleavage of the disulfide linkages. A model drug 5-aminosalicylic acid (5-ASA) could be loaded efficiently into starch nanoparticles and the in vitro drug release behaviors were also studied. The results suggested that the disulfide crosslinked starch nanoparticles exhibited an accelerated drug release behavior in the presence of DTT. In vitro methyl thiazolyl tetrazolium (MTT) assays indicated that BAC crosslinked starch nanoparticles had a good biocompatibility when cocultured with human HeLa cancer cells. Hence, with excellent biocompatibility and biodegradability, and rapid drug release in response to DTT, BAC crosslinked starch nanoparticles showed a great potential as a biomaterial carrier for the application of drug controlled release. In contrast to BAC crosslinked starch nanoparticles, N,N-methylenebisacrylamine (MBA) crosslinked starch nanoparticles were prepared as the control without the disulfide linkages. PMID:24463097

  16. Thermomechanical Properties, Antibiotic Release, and Bioactivity of a Sterilized Cyclodextrin Drug Delivery System.

    PubMed

    Halpern, Jeffrey M; Gormley, Catherine A; Keech, Melissa; von Recum, Horst A

    2014-05-14

    Various local drug delivery devices and coatings are being developed as slow, sustained release mechanism for drugs, yet the polymers are typically not evaluated after commercial sterilization techniques. We examine the effect that commercial sterilization techniques have on the physical, mechanical, and drug delivery properties of polyurethane polymers. Specifically we tested cyclodextrin-hexamethyl diisocyanate crosslinked polymers before and after autoclave, ethylene oxide, and gamma radiation sterilization processes. We found that there is no significant change in the properties of polymers sterilized by ethylene oxide and gamma radiation compared to non-sterilized polymers. Polymers sterilized by autoclave showed increased tensile strength (p<0.0001) compared to non-sterilized polymers . In the release of drugs, which were loaded after the autoclave sterilization process, we observed a prolonged release (p<0.05) and a prolonged therapeutic effect (p<0.05) but less drug loading (p<0.0001) compared to non-sterilized polymers. The change in the release profile and tensile strength in polymers sterilized by autoclave was interpreted as being caused by additional crosslinking from residual, unreacted, or partially-reacted crosslinker contained within the polymer. Autoclaving therefore represents additional thermo-processing to modify rate and dose from polyurethanes and other materials. PMID:24949201

  17. Controlled release drug delivery systems to improve post-operative pharmacotherapy.

    PubMed

    Bhusal, Prabhat; Harrison, Jeff; Sharma, Manisha; Jones, David S; Hill, Andrew G; Svirskis, Darren

    2016-10-01

    Over 230 million surgical procedures are conducted worldwide each year with numbers increasing. Pain, undesirable inflammation and infection are common complications experienced by patients following surgery. Opioids, non-steroidal anti-inflammatory drugs (NSAIDs), local anaesthetics (LAs) and antibiotics are the commonly administered drugs peri-operatively to manage these complications. Post-operative pharmacotherapy is typically achieved using immediate-release dosage forms of drugs, which lead to issues around fluctuating plasma concentrations, systemic adverse effects and poor patient adherence. Controlled release (CR) systems for certain medicines including opioids, NSAIDs and antibiotics have demonstrably enhanced treatment efficacy in the post-surgical setting. However, challenges remain to ensure patient safety while achieving individual therapeutic needs. Newer CR systems in the research and development pipeline have a high level of control over medicine release, which can be initiated, tuned or stopped on-demand. Future systems will self-regulate drug release in response to biological markers providing precise individualized therapy. In this review, we cover currently adopted CR systems in post-operative pharmacotherapy, including drug eluting medical devices, and highlight a series of examples of novel CR technologies that have the potential for translation into post-surgical settings to improve medication efficacy and enhance post-surgical recovery. PMID:27329201

  18. Doxorubicin loaded nanodiamond-silk spheres for fluorescence tracking and controlled drug release

    PubMed Central

    Khalid, Asma; Mitropoulos, Alexander N.; Marelli, Benedetto; Tomljenovic-Hanic, Snjezana; Omenetto, Fiorenzo G.

    2015-01-01

    Nanoparticle (NP) based technologies have proved to be considerably beneficial for advances in biomedicine especially in the areas of disease detection, drug delivery and bioimaging. Over the last few decades, NPs have garnered interest for their exemplary impacts on the detection, treatment, and prevention of cancer. The full potential of these technologies are yet to be employed for clinical use. The ongoing research and development in this field demands single multifunctional composite materials that can be employed simultaneously for drug delivery and biomedical imaging. In this manuscript, a unique combination of silk fibroin (SF) and nanodiamonds (NDs) in the form of nanospheres are fabricated and investigated. The spheres were loaded with the anthracyline Doxorubicin (DoX) and the drug release kinetics for these ND-SF-DoX (NDSX) spheres were studied. NDs provided the fluorescence modality for imaging while the degradable SF spheres stabilized and released the drug in a controlled manner. The emission and structural properties of the spheres were characterized during drug release. The degradability of SF and the subsequent release of DoX from the spheres were monitored through fluorescence of NDs inside the spheres. This research demonstrates the enormous potential of the ND-SF nanocomposite platforms for diagnostic and therapeutic purposes, which are both important for pharmaceutical research and clinical settings. PMID:26819823

  19. Smart photothermal-triggered bilayer phase transition in AuNPs-liposomes to release drug.

    PubMed

    An, Xueqin; Zhan, Fan; Zhu, Yinyan

    2013-01-29

    Novel thermosensitive liposomes with embedded Au nanoparticles (AuNPs) in the liposome bilayer were prepared by a combination method of film build and supercritical CO(2) incubation. These AuNPs-liposomes possess AuNPs that are embedded in the bilayer and a drug that is encapsulated in the central aqueous compartment. The AuNPs in the liposomes can strongly absorb light energy and efficiently convert the absorbed energy to heat. The localized heat induces a phase transition in the liposome bilayer and releases the drug. The drug release from the AuNPs-liposomes can be controlled by the irradiation time and AuNPs concentration in the AuNPs-liposomes at room temperature, where the AuNPs function as a nanoswitch for triggering drug release both spatially and temporally. The results suggest that drug release from the AuNPs-liposomes is due to a photothermic effect that induces phase transition of the liposomes rather than destruction of the liposome bilayer. PMID:23286691

  20. Alginate/quaternized carboxymethyl chitosan/clay nanocomposite microspheres: preparation and drug-controlled release behavior.

    PubMed

    Liu, Bo; Luo, Jiwen; Wang, Xiaoying; Lu, Junxiang; Deng, Hongbing; Sun, Runcang

    2013-01-01

    Drug-delivery systems, using natural drug carriers, have become increasingly important because of their nontoxicity and biodegradability. In this study, firstly, quaternized carboxymethyl chitosan (QCMC) was intercalated into the interlayer of organic montmorillonite (OMMT) to obtain the QCMC/OMMT nanocomposites, their structure, morphology, and thermal stability were investigated. Next, crosslinked alginate/QCMC/OMMT (AQCOM) microsphere was obtained by crosslinking with CaCl2, and the drug-controlled release behavior was evaluated with bovine serum albumin (BSA) as model drug. The results suggested that, carboxyl groups in alginate and QCMC crosslinked with Ca(2+), quaternary ammonium groups in QCMC or OMMT electrostatically interacted with carboxyl groups in alginate, and there was stable three-dimensional network in AQCOM microsphere. The swelling ratio of AQCOM microspheres decreased with the increase of OMMT content, the lowest one was only about 45% compared to the microsphere without OMMT of 197%. Besides, the in vitro release results for BSA indicated that the AQCOM microsphere displayed more excellent encapsulation and controlled release capacities than the microsphere without OMMT. The in vitro active cutaneous anaphylaxis test was carried out on Guinea pigs, which revealed that AQCOM microsphere did not cause anaphylaxis. Therefore, QCMC/OMMT nanocomposites from natural materials are considerably suitable to apply as drug-controlled release carriers. PMID:23565870

  1. Structure and drug release in a crosslinked poly(ethylene oxide) hydrogel.

    PubMed

    Shekunov, Boris Y; Chattopadhyay, Pratibhash; Tong, Henry H Y; Chow, Albert H L; Grossmann, J Günter

    2007-05-01

    Hydrogels are a continuously expanding class of pharmaceutical polymers designed for sustained or controlled drug release. The structure and intermolecular interactions in such systems define their macroscopic properties. The aim of this study was to investigate the mechanism of swelling, drug impregnation, and drug release from poly(ethylene oxide) (PEO) gel crosslinked by urethane bonds. A combination of SAXS/WAXS/SANS techniques enabled us to determine the phase transition between lamellar and extended gel network, and to apply different descriptions of crystallinity, based on lamellar and crystal lattice structures. It is shown that even low (1-7% w/w) loading of model drugs acetaminophen and caffeine, produced significant disorder in the polymer matrix. This effect was particularly pronounced for acetaminophen due to its specific ability to form complexes with PEO. The drug-release profiles were analyzed using a general cubic equation, proposed for this work, which allowed us to determine the gel hydration velocity. The results indicate that the release profiles correlate inversely with the polymer crystallinity. PMID:17455363

  2. A multiscale mechanism of drug release from polymeric matrices: confirmation through a nonlinear theoretical model.

    PubMed

    Bacaita, E S; Agop, M

    2016-08-21

    In this paper, we propose a new approach for the dynamics of drug delivery systems, assimilated to complex systems, an approach based on concepts like fractality, non-differentiability, and multiscale evolution. The main advantage of using these concepts is the possibility of eliminating the approximations used in the standard approach by replacing complexity with fractality, that imposes, in mathematical terms, the mandatory use of the non-differential character of defined physical quantities. The theoretical model presented, validated for other physical systems, demonstrates its functionality also for drug delivery systems, highlighting, in addition, new insights into the complexity of this system. The spatio-temporal scales of system evolution are characterized through the fractality degree, as a measure of the complexity of the phenomena occurring at each scale. Numerical analysis of the experiment showed that the overall drug release kinetics can be obtained by composing "smaller release kinetics" occurring at scales appropriate for each phase of the drug release mechanism, phases whose expansion depends on the system density. Moreover, the uncertainties in establishing the exact limits of the phases were removed by applying the principle of scale superposition, resulting in a global fractality degree corresponding to the entire release kinetics. Even if the theoretical model is perfectible by identifying constants specific to each delivery system, this paper is intended to be the beginning of an alternative approach to drug delivery mechanisms. PMID:27436760

  3. A new scleroglucan/borax hydrogel: swelling and drug release studies.

    PubMed

    Coviello, Tommasina; Grassi, Mario; Palleschi, Antonio; Bocchinfuso, Gianfranco; Coluzzi, Gina; Banishoeib, Fateme; Alhaique, Franco

    2005-01-31

    The aim of the work was the characterization of a new polysaccharidic physical hydrogel, obtained from Scleroglucan (Sclg) and borax, following water uptake and dimension variations during the swelling process. Furthermore, the release of molecules of different size (Theophylline (TPH), Vitamin B12 (Vit. B12) and Myoglobin (MGB)) from the gel and from the dried system used as a matrix for tablets was studied. The increase of weight of the tablets with and without the loaded drugs was followed together with the relative variation of the dimensions. The dry matrix, in the form of tablets was capable, during the swelling process, to incorporate a relevant amount of solvent (ca. 20 g water/g dried matrix), without dissolving in the medium, leading to a surprisingly noticeable anisotropic swelling that can be correlated with a peculiar supramolecular structure of the system induced by compression. Obtained results indicate that the new hydrogel can be suitable for sustained drug release formulations. The delivery from the matrix is deeply dependent on the size of the tested model drugs. The experimental release data obtained from the gel were satisfactorily fitted by an appropriate theoretical approach and the relative drug diffusion coefficients in the hydrogel were estimated. The release profiles of TPH, Vit. B12 and MGB from the tablets have been analyzed in terms of a new mathematical approach that allows calculating of permeability values of the loaded drugs. PMID:15652203

  4. Biointerfacing polymeric microcapsules for in vivo near-infrared light-triggered drug release

    NASA Astrophysics Data System (ADS)

    Shao, Jingxin; Xuan, Mingjun; Si, Tieyan; Dai, Luru; He, Qiang

    2015-11-01

    Seeking safe and effective water-soluble drug carriers is of great significance in nanomedicine. To achieve this goal, we present a novel drug delivery system based on biointerfacing hollow polymeric microcapsules for effectively encapsulating water-soluble antitumor drug and gold nanorod (GNR) functionalization for triggered release of therapeutic drugs on-demand using low power near-infrared (NIR) radiation. The surface of polymeric microcapsules is covered with fluidic lipid bilayers to decrease the permeability of the wall of polymeric capsules. The temperature increase upon NIR illumination deconstructs the structure of the lipid membrane and polyelectrolyte multilayers, which in turn results in the rapid release of encapsulated water-soluble drug. In vivo antitumor tests demonstrate that this microcapsule has the effective ability of inhibiting tumor growth and preventing metastases. Real time in vivo fluorescence imaging results confirm that capsules can be excreted gradually from the animal body which in turn demonstrates the biocompatibility and biodegradation of these biointerfacing GNR-microcapsules. This intelligent system provides a novel anticancer platform with the advantages of controlled release, biological friendliness and credible biosafety.Seeking safe and effective water-soluble drug carriers is of great significance in nanomedicine. To achieve this goal, we present a novel drug delivery system based on biointerfacing hollow polymeric microcapsules for effectively encapsulating water-soluble antitumor drug and gold nanorod (GNR) functionalization for triggered release of therapeutic drugs on-demand using low power near-infrared (NIR) radiation. The surface of polymeric microcapsules is covered with fluidic lipid bilayers to decrease the permeability of the wall of polymeric capsules. The temperature increase upon NIR illumination deconstructs the structure of the lipid membrane and polyelectrolyte multilayers, which in turn results in the rapid

  5. Inclusion of telmisartan in mesocellular foam nanoparticles: drug loading and release property.

    PubMed

    Zhang, Yanzhuo; Jiang, Tongying; Zhang, Qiang; Wang, Siling

    2010-09-01

    Spherical mesocellular foam (MCF) with a continuous 3-D pore system was synthesized using Pluronic 123 triblock polymer (P123) as a surfactant coupled with cetyltrimethyl ammonium bromide (CTAB) as a co-surfactant. The feasibility of the prepared MCF nanoparticles for oral drug delivery was studied. A model drug, telmisartan (TEL), was loaded onto MCF via a procedure involving a combination of adsorption equilibrium and solvent evaporation. The drug-release rate and the drug loading efficiency of spherical MCF were compared with those of fibrous SBA-15. Investigations using nitrogen adsorption, scanning electron microscopy (SEM), transmission electron microscopy (TEM), wide-angle X-ray scattering (WXRS), differential scanning calorimetry (DSC) and HPLC demonstrated the successful incorporation of TEL into the MCF host. It is found that spherical MCF has a high drug loading efficiency up to 42.9% (drug weight/total weight) and higher than that of SBA-15 with a pore diameter of 6.5 nm. It is shown that a fast release rate of TEL was obtained from MCF compared with SBA-15 and pure crystalline TEL using enzyme-free simulated gastric fluid (pH 1.2) and intestinal fluid (pH 6.8). We believe that the present study will help in the design of oral drug delivery systems for the dissolution enhancement of water-insoluble drugs. PMID:20685333

  6. Polyacrylic acid modified upconversion nanoparticles for simultaneous pH-triggered drug delivery and release imaging.

    PubMed

    Jia, Xuekun; Yin, Jinjin; He, Dinggeng; He, Xiaoxiao; Wang, Kemin; Chen, Mian; Li, Yuhong

    2013-12-01

    A poly(acrylicacid)-modified NaYF4:Yb, Er upconversion nanoparticles (PAA-UCNPs) with dual functions of drug delivery and release imaging have been successfully developed. The PAA polymer coated on the surface of UCNPs serve as a pH-sensitive nanovalve for loading drug molecules via electrostatic interaction. The drug-loading efficiency of the PAA-UCNPs was investigated by using doxorubicin hydrochloride (DOX) as a model anticancer drug to evaluate their potential as a delivery system. Results showed loading and releasing of DOX from PAA-UCNPs were controlled by varying pH, with high encapsulation rate at weak alkaline conditions and an increased drug dissociation rate in acidic environment, which is favorable for construct a pH-responsive controlled drug delivery system. The in vitro cytotoxicity test using HeLa cell line indicated that the DOX loaded PAA-UCNPs (DOX@PAA-UCNPs) were distinctly cytotoxic to HeLa cells, while the PAA-UCNPs were highly biocompatible and suitable to use as drug carriers. Furthermore, the upconversion fluorescence resonance energy transfer (UFRET) imaging through the two-photon laser scanning microscopy (TLSM) revealed the time course of intracellular delivery of DOX from DOX@PAA-UCNPs. Thus, PAA-UCNPs are effective for constructing pH-responsive controlled drug delivery systems for multi-functional cancer therapy and imaging. PMID:24266261

  7. Nicotinic acid: new/old drug. Immediate or sustained release: too risky for a drug with no proven benefit.

    PubMed

    2006-12-01

    (1) For patients with hypercholesterolaemia requiring primary or secondary prevention, pravastatin, simvastatin and atorvastatin have a proven benefit in terms of mortality and/or morbidity. Gemfibrozil and cholestyramine have a proven impact on morbidity. (2) The lipid-lowering properties of immediate-release nicotinic acid have been known for about 50 years, as have its frequent and sometimes severe adverse effects. About 70% of patients experience cutaneous flushing, and 20-30% develop gastrointestinal adverse effects. Hepatotoxic effects occur in about 2% of patients, especially in those using high daily doses or sustained-release formulations. (3) The clinical evaluation of immediate-release nicotinic acid is mainly based on two comparative placebo-controlled trials. One, involving 5000 patients monitored on average for 15 years, showed no effect on survival. One trial suggested that immediate-release nicotinic acid reduced the risk of recurrent myocardial infarction. (4) Sustained-release nicotinic acid has not been evaluated in terms of its effect on morbidity or mortality. It has been shown to lower LDL cholesterol and triglyceride levels and to raise the HDL cholesterol level. (5) This new pharmaceutical formulation has a profile and frequency of known adverse effects similar to those of immediate-release nicotinic acid. (6) When hypercholesterolaemia persists despite an appropriate diet, it is best to use one drug with a proven preventive impact on mortality and/or morbidity. This is not the case for sustained-release nicotinic acid. (7) When statin therapy is inadequate, it remains to be shown whether adding another cholesterol-lowering drug is beneficial in terms of morbidity and mortality. If, in rare cases, combination with a statin is envisaged, it is best to use gemfibrozil or cholestyramine. Note that gemfibrozil should only be combined with a statin with the greatest caution. PMID:17165243

  8. Local bacteria affect the efficacy of chemotherapeutic drugs

    PubMed Central

    Lehouritis, Panos; Cummins, Joanne; Stanton, Michael; Murphy, Carola T.; McCarthy, Florence O.; Reid, Gregor; Urbaniak, Camilla; Byrne, William L.; Tangney, Mark

    2015-01-01

    In this study, the potential effects of bacteria on the efficacy of frequently used chemotherapies was examined. Bacteria and cancer cell lines were examined in vitro and in vivo for changes in the efficacy of cancer cell killing mediated by chemotherapeutic agents. Of 30 drugs examined in vitro, the efficacy of 10 was found to be significantly inhibited by certain bacteria, while the same bacteria improved the efficacy of six others. HPLC and mass spectrometry analyses of sample drugs (gemcitabine, fludarabine, cladribine, CB1954) demonstrated modification of drug chemical structure. The chemoresistance or increased cytotoxicity observed in vitro with sample drugs (gemcitabine and CB1954) was replicated in in vivo murine subcutaneous tumour models. These findings suggest that bacterial presence in the body due to systemic or local infection may influence tumour responses or off-target toxicity during chemotherapy. PMID:26416623

  9. FACTORS AFFECTING THE DEPOSITION OF INHALED POROUS DRUG PARTICLES

    EPA Science Inventory

    Abstract
    Recent findings indicate that the inhalation of large manufactured porous particles may be particularly effective for drug delivery. In this study, a mathematical model was employed to systematically investigate the effects of particle size, particle density, aerosol ...

  10. Investigation of Release Pattern of a Drug with Low Solubility Through Asymmetric Membrane Capsules

    PubMed Central

    Sahoo, P. K.; Makar, Harleen

    2013-01-01

    Asymmetric membrane capsules are a type of osmotic drug delivery systems. They are nondisintegrating capsules, which utilize osmotic pressure to drive the drug outwards for controlled delivery. Preceded by systems such as elementary osmotic pump, controlled porosity osmotic pump, single composition osmotic tablet this system has the advantage of simple and easy fabrication as it obviates the necessity of drilling an orifice into the drug delivery system. Moreover; it seems to be a low-cost alternative. The cellulose acetate capsule shell, on coming in contact with the aqueous medium shows in situ pore formation due to leaching of pore formers, which have been incorporated into the shell forming solution. Until date, a number of osmotic agents to the likes of sodium chloride, mannitol has been used to build up osmotic pressure inside the cell. The system is endowed with high water flux, which is a plus point for delivery of poorly soluble drugs like cephalexin in terms of increasing release rates. Studies envisaged in this research include the effect of different concentrations of different pore formers on in vitro drug release as well as the effect of modification of inner contents of the capsule. The system was successful in producing a gradual release of drug for 12 h. PMID:24019570

  11. Targeted and controlled anticancer drug delivery and release with magnetoelectric nanoparticles

    PubMed Central

    Rodzinski, Alexandra; Guduru, Rakesh; Liang, Ping; Hadjikhani, Ali; Stewart, Tiffanie; Stimphil, Emmanuel; Runowicz, Carolyn; Cote, Richard; Altman, Norman; Datar, Ram; Khizroev, Sakhrat

    2016-01-01

    It is a challenge to eradicate tumor cells while sparing normal cells. We used magnetoelectric nanoparticles (MENs) to control drug delivery and release. The physics is due to electric-field interactions (i) between MENs and a drug and (ii) between drug-loaded MENs and cells. MENs distinguish cancer cells from normal cells through the membrane’s electric properties; cancer cells have a significantly smaller threshold field to induce electroporation. In vitro and in vivo studies (nude mice with SKOV-3 xenografts) showed that (i) drug (paclitaxel (PTX)) could be attached to MENs (30-nm CoFe2O4@BaTiO3 nanostructures) through surface functionalization to avoid its premature release, (ii) drug-loaded MENs could be delivered into cancer cells via application of a d.c. field (~100 Oe), and (iii) the drug could be released off MENs on demand via application of an a.c. field (~50 Oe, 100 Hz). The cell lysate content was measured with scanning probe microscopy and spectrophotometry. MENs and control ferromagnetic and polymer nanoparticles conjugated with HER2-neu antibodies, all loaded with PTX were weekly administrated intravenously. Only the mice treated with PTX-loaded MENs (15/200 μg) in a field for three months were completely cured, as confirmed through infrared imaging and post-euthanasia histology studies via energy-dispersive spectroscopy and immunohistochemistry. PMID:26875783

  12. Targeted and controlled anticancer drug delivery and release with magnetoelectric nanoparticles

    NASA Astrophysics Data System (ADS)

    Rodzinski, Alexandra; Guduru, Rakesh; Liang, Ping; Hadjikhani, Ali; Stewart, Tiffanie; Stimphil, Emmanuel; Runowicz, Carolyn; Cote, Richard; Altman, Norman; Datar, Ram; Khizroev, Sakhrat

    2016-02-01

    It is a challenge to eradicate tumor cells while sparing normal cells. We used magnetoelectric nanoparticles (MENs) to control drug delivery and release. The physics is due to electric-field interactions (i) between MENs and a drug and (ii) between drug-loaded MENs and cells. MENs distinguish cancer cells from normal cells through the membrane’s electric properties; cancer cells have a significantly smaller threshold field to induce electroporation. In vitro and in vivo studies (nude mice with SKOV-3 xenografts) showed that (i) drug (paclitaxel (PTX)) could be attached to MENs (30-nm CoFe2O4@BaTiO3 nanostructures) through surface functionalization to avoid its premature release, (ii) drug-loaded MENs could be delivered into cancer cells via application of a d.c. field (~100 Oe), and (iii) the drug could be released off MENs on demand via application of an a.c. field (~50 Oe, 100 Hz). The cell lysate content was measured with scanning probe microscopy and spectrophotometry. MENs and control ferromagnetic and polymer nanoparticles conjugated with HER2-neu antibodies, all loaded with PTX were weekly administrated intravenously. Only the mice treated with PTX-loaded MENs (15/200 μg) in a field for three months were completely cured, as confirmed through infrared imaging and post-euthanasia histology studies via energy-dispersive spectroscopy and immunohistochemistry.

  13. Targeted and controlled anticancer drug delivery and release with magnetoelectric nanoparticles.

    PubMed

    Rodzinski, Alexandra; Guduru, Rakesh; Liang, Ping; Hadjikhani, Ali; Stewart, Tiffanie; Stimphil, Emmanuel; Runowicz, Carolyn; Cote, Richard; Altman, Norman; Datar, Ram; Khizroev, Sakhrat

    2016-01-01

    It is a challenge to eradicate tumor cells while sparing normal cells. We used magnetoelectric nanoparticles (MENs) to control drug delivery and release. The physics is due to electric-field interactions (i) between MENs and a drug and (ii) between drug-loaded MENs and cells. MENs distinguish cancer cells from normal cells through the membrane's electric properties; cancer cells have a significantly smaller threshold field to induce electroporation. In vitro and in vivo studies (nude mice with SKOV-3 xenografts) showed that (i) drug (paclitaxel (PTX)) could be attached to MENs (30-nm CoFe2O4@BaTiO3 nanostructures) through surface functionalization to avoid its premature release, (ii) drug-loaded MENs could be delivered into cancer cells via application of a d.c. field (~100 Oe), and (iii) the drug could be released off MENs on demand via application of an a.c. field (~50 Oe, 100 Hz). The cell lysate content was measured with scanning probe microscopy and spectrophotometry. MENs and control ferromagnetic and polymer nanoparticles conjugated with HER2-neu antibodies, all loaded with PTX were weekly administrated intravenously. Only the mice treated with PTX-loaded MENs (15/200 μg) in a field for three months were completely cured, as confirmed through infrared imaging and post-euthanasia histology studies via energy-dispersive spectroscopy and immunohistochemistry. PMID:26875783

  14. Control of photo-induced drug release by the use of conformational change of DNA.

    PubMed

    Tanabe, Kazuhito; Inasaki, Takeshi; Okamoto, Akimitsu; Nishimoto, Sei-ichi; Saito, Isao

    2002-01-01

    Photo-induced drug release system which was controlled by triplet quenching using the molecular beacon strategy of photoreactive oligodeoxynucleotides (P-ODN) was developed. The strand ends of P-ODN were modified with a phenacyl ester of biotin and naphthalene as photoreactive group and triplet quencher, respectively. Photoirradiation to P-ODN in the presence of complementary DNA caused an efficient release of biotin. In contrast, the biotin release was suppressed in the absence of complementary DNA by the intramolecular triplet quenching in the stem-and-loop structure of P-ODN. PMID:12903158

  15. Prenatal Drug Exposure Affects Neonatal Brain Functional Connectivity

    PubMed Central

    Salzwedel, Andrew P.; Vachet, Clement; Gerig, Guido; Lin, Weili

    2015-01-01

    Prenatal drug exposure, particularly prenatal cocaine exposure (PCE), incurs great public and scientific interest because of its associated neurodevelopmental consequences. However, the neural underpinnings of PCE remain essentially uncharted, and existing studies in school-aged children and adolescents are confounded greatly by postnatal environmental factors. In this study, leveraging a large neonate sample (N = 152) and non-invasive resting-state functional magnetic resonance imaging, we compared human infants with PCE comorbid with other drugs (such as nicotine, alcohol, marijuana, and antidepressant) with infants with similar non-cocaine poly drug exposure and drug-free controls. We aimed to characterize the neural correlates of PCE based on functional connectivity measurements of the amygdala and insula at the earliest stage of development. Our results revealed common drug exposure-related connectivity disruptions within the amygdala–frontal, insula–frontal, and insula–sensorimotor circuits. Moreover, a cocaine-specific effect was detected within a subregion of the amygdala–frontal network. This pathway is thought to play an important role in arousal regulation, which has been shown to be irregular in PCE infants and adolescents. These novel results provide the earliest human-based functional delineations of the neural-developmental consequences of prenatal drug exposure and thus open a new window for the advancement of effective strategies aimed at early risk identification and intervention. PMID:25855194

  16. Prenatal drug exposure affects neonatal brain functional connectivity.

    PubMed

    Salzwedel, Andrew P; Grewen, Karen M; Vachet, Clement; Gerig, Guido; Lin, Weili; Gao, Wei

    2015-04-01

    Prenatal drug exposure, particularly prenatal cocaine exposure (PCE), incurs great public and scientific interest because of its associated neurodevelopmental consequences. However, the neural underpinnings of PCE remain essentially uncharted, and existing studies in school-aged children and adolescents are confounded greatly by postnatal environmental factors. In this study, leveraging a large neonate sample (N = 152) and non-invasive resting-state functional magnetic resonance imaging, we compared human infants with PCE comorbid with other drugs (such as nicotine, alcohol, marijuana, and antidepressant) with infants with similar non-cocaine poly drug exposure and drug-free controls. We aimed to characterize the neural correlates of PCE based on functional connectivity measurements of the amygdala and insula at the earliest stage of development. Our results revealed common drug exposure-related connectivity disruptions within the amygdala-frontal, insula-frontal, and insula-sensorimotor circuits. Moreover, a cocaine-specific effect was detected within a subregion of the amygdala-frontal network. This pathway is thought to play an important role in arousal regulation, which has been shown to be irregular in PCE infants and adolescents. These novel results provide the earliest human-based functional delineations of the neural-developmental consequences of prenatal drug exposure and thus open a new window for the advancement of effective strategies aimed at early risk identification and intervention. PMID:25855194

  17. Exploitation of novel gum Prunus cerasoides as mucoadhesive beads for a controlled-release drug delivery.

    PubMed

    Seelan, T Veenus; Kumari, Henry Linda Jeeva; Kishore, Narra; Selvamani, Palanisamy; Lalhlenmawia, H; Thanzami, K; Pachuau, Lalduhsanga; Ruckmani, Kandasamy

    2016-04-01

    The present study deals with the formulation of pH-sensitive mucoadhesive beads using natural gum isolated from Prunus cerasoides (PC) in combination with sodium alginate (SA) for the controlled release of diclofenac sodium (DS). PC and SA composite (PC-SA), DS loaded SA (DS-SA) and DS loaded PC-SA (DS-PC-SA) beads were prepared by ionotropic gelation method. The absence of interaction between DS and PC-SA was shown by FTIR, DSC and TGA analyses. The optimized DS-PC-SA formulation exhibited mucoadhesive property and the controlled release of DS was achieved 68% in 12h. The in vitro release kinetics follows zero order with anomalous diffusion mechanism. Therefore, the formulated mucoadhesive beads with the novel gum are preferable for the controlled release of DS by prolonging the residence time of the drug in the gastrointestinal tract, overcoming the problems associated with the immediate release dosage forms of DS. PMID:26772921

  18. Real-Time Drug Release Analysis of Enzyme and pH Responsive Polysaccharide Nanovesicles.

    PubMed

    Pramod, Poothayil Subash; Deshpande, Nilesh Umakant; Jayakannan, Manickam

    2015-08-20

    The accurate estimation of drug release kinetics of polymeric vehicles is an indispensable prerequisite for the developments of successful drug carriers for cancer therapy. The present investigation reports the development of time-resolved fluorescence spectroscopic approach for the real-time release kinetics of fluorophore loaded polysaccharide vesicles that are potential vectors in cancer treatment. The polysaccharide vesicles were custom designed with appropriate enzyme and pH responsiveness and loaded with water-soluble biocompatible fluorophore Rhodamine B (Rh-B). The semipermeable membrane dialysis method along with steady state absorbance spectroscopic technique was found to be inaccurate for the estimation of drug release. Time correlated single photon counting (TCSPC) technique was found to exhibit significant difference in excited state decay profiles and fluorescent lifetime of Rh-B in the free and polymer bound states. This enabled the establishment of real-time drug release protocols by TCSPC method for polysaccharide vesicles that are responsible to pH and enzyme with respect to intracellular compartments. Real-time analysis predicted the release kinetics 20-25% higher accuracy when compared to the dialysis method under in vitro conditions. Moreover, the ability of enzyme to cleave the polysaccharide vesicles was further validated by docking studies. The positioning of the molecules in active site of enzyme and the binding energy data were generated using AUTODOCK program to study the rupture of polysaccharide vesicles. This new TCSPC technique could be very useful for studying the drug release pattern of synthetic polymer vesicles loaded with Rh-B fluorophore. PMID:26237375

  19. Drug-releasing nano-engineered titanium implants: therapeutic efficacy in 3D cell culture model, controlled release and stability.

    PubMed

    Gulati, Karan; Kogawa, Masakazu; Prideaux, Matthew; Findlay, David M; Atkins, Gerald J; Losic, Dusan

    2016-12-01

    There is an ongoing demand for new approaches for treating localized bone pathologies. Here we propose a new strategy for treatment of such conditions, via local delivery of hormones/drugs to the trauma site using drug releasing nano-engineered implants. The proposed implants were prepared in the form of small Ti wires/needles with a nano-engineered oxide layer composed of array of titania nanotubes (TNTs). TNTs implants were inserted into a 3D collagen gel matrix containing human osteoblast-like, and the results confirmed cell migration onto the implants and their attachment and spread. To investigate therapeutic efficacy, TNTs/Ti wires loaded with parathyroid hormone (PTH), an approved anabolic therapeutic for the treatment of severe bone fractures, were inserted into 3D gels containing osteoblast-like cells. Gene expression studies revealed a suppression of SOST (sclerostin) and an increase in RANKL (receptor activator of nuclear factor kappa-B ligand) mRNA expression, confirming the release of PTH from TNTs at concentrations sufficient to alter cell function. The performance of the TNTs wire implants using an example of a drug needed at relatively higher concentrations, the anti-inflammatory drug indomethacin, is also demonstrated. Finally, the mechanical stability of the prepared implants was tested by their insertion into bovine trabecular bone cores ex vivo followed by retrieval, which confirmed the robustness of the TNT structures. This study provides proof of principle for the suitability of the TNT/Ti wire implants for localized bone therapy, which can be customized to cater for specific therapeutic requirements. PMID:27612777

  20. On the exfoliating polymeric cellular dosage forms for immediate drug release.

    PubMed

    Blaesi, Aron H; Saka, Nannaji

    2016-06-01

    The most prevalent pharmaceutical dosage forms at present-the oral immediate-release tablets and capsules-are granular solids. Though effective in releasing drug rapidly, development and manufacture of such dosage forms are fraught with difficulties inherent to particulate processing. Predictable dosage form manufacture could be achieved by liquid-based processing, but cast solid dosage forms are not suitable for immediate drug release due to their resistance to fluid percolation. To overcome this limitation, we have recently introduced cellular dosage forms that can be readily prepared from polymeric melts. It has been shown that open-cell structures comprising polyethylene glycol 8000 (PEG 8k) excipient and a drug exfoliate upon immersion in a dissolution medium. The drug is then released rapidly due to the large specific surface area of the exfoliations. In this work, we vary the molecular weight of the PEG excipient and investigate its effect on the drug release kinetics of structures with predominantly open-cell topology. We demonstrate that the exfoliation rate decreases substantially if the excipient molecular weight is increased from 12 to 100kg/mol, which causes the drug dissolution time to increase by more than a factor of ten. A model is then developed to elucidate the exfoliation behavior of cellular structures. Diverse transport processes are considered: percolation due to capillarity, diffusion of dissolution medium through the cell walls, and viscous flow of the saturated excipient. It is found that the lower exfoliation rate and the longer dissolution time of the dosage forms with higher excipient molecular weight are primarily due to the greater viscosity of the cell walls after fluid penetration. PMID:27045468

  1. Versatile FRET-Based Mesoporous Silica Nanoparticles for Real-Time Monitoring of Drug Release

    PubMed Central

    Lai, Jinping; Shah, Birju P.; Garfunkel, Eric; Lee, Ki-Bum

    2013-01-01

    We describe the development of a versatile fluorescence resonance energy transfer (FRET)-based real-time monitoring system, consisting of (a) coumarin-labeled-cysteine tethered mesoporous silica nanoparticles (MSNs) as the drug carrier, (b) a fluorescein isothiocyanate-β-cyclodextrin (FITC-β-CD) as redox-responsive molecular valve blocking the pores, and (c) a FRET donor-acceptor pair of coumarin and FITC integrated within the pore-unlocking event, thereby allowing for monitoring the release of drugs from the pores in real-time. Under non-reducing conditions, when the disulfide bond is intact, the close proximity between coumarin and FITC on the surface of MSNs results in FRET from coumarin to FITC. However, in the presence of the redox stimuli like glutathione (GSH), the disulfide bond is cleaved which leads to the removal of molecular valve (FITC-β-CD), thus triggering drug release and eliminating FRET. By engineering such a FRET-active donor-acceptor structure within the redox-responsive molecular valve, we can monitor the release of the drugs entrapped within the pores of the MSN nanocarrier, following the change in the FRET signal. We have demonstrated that, any exogenous or endogenous change in the GSH concentration will result in a change in the extent of drug release as well as a concurrent change in the FRET signal, allowing us to extend the applications of our FRET-based MSNs for monitoring the release of any type of drug molecule in real-time. PMID:23445171

  2. Formulation and characterization of sustained release dosage form of moisture sensitive drug

    PubMed Central

    Patel, Priya; Dave, Abhishek; Vasava, Amit; Patel, Paresh

    2015-01-01

    Objective: The purpose of this study was to prepare sustained release tablet of moisture sensitive drug like Ranitidine Hydrochloride for treatment of gastroesophageal reflux disease along with the improvement of moisture stability to get better therapeutic efficacy. Materials and Methods: Pan coating technique was used for coating of the tablet. Film coating was done using Eudragit RLPO and Eugragit EPO as coating polymer. 32 full factorial design was applied for optimization purpose, and 9 runs were conducted. In that Eudragit RLPO and Eudragit EPO taken as an independent variables and moisture gain and Cummulative Drug Release (CDR) were taken as dependent variables. Drug and excipient compatibility was done using differential scanning calorimetry and Fourier transform infrared spectroscopy study. The tablet was evaluated for precompression parameter and all postcompression parameter. Stability study was carried out at room temperature (30°C ± 2°C/65% ± 5% relative humidity). Final formulation was compared with marketed formulation RANTEC 300. Result: Tablets were passing out all precompression parameter along with postcompression parameter. Stability study shows that the parameter such as hardness, friability, and dissolution are in the range. Hence, there is no significant change shown after stability study. Our final formulation was compared with marketed formulation RANTEC 300 and result demonstrates that our final formulation have less moisture gain and give release up to 12 h. Conclusion: The result of present study demonstrates that final formulation has less moisture gain and getting desired CDR for sustained release of drug. On the basis of all study, it was concluded that the tablet was coated by combination of Eudragit RLPO 10% and Eudragit EPO 10% give better result. This formation provided promising approach for the drug release up to 12 h for moisture sensitive drug like ranitidine hydrochloride. PMID:25838994

  3. Single and Dual Drug Release Patterns from Shellac Wax-Lutrol Matrix Tablets Fabricated with Fusion and Molding Techniques

    PubMed Central

    Phaechamud, T.; Choncheewa, C.

    2015-01-01

    The objective of this investigation was to prepare the shellac wax matrix tablets by fusion and molding technique incorporated with Lutrol in different ratios to modify the hydrophobicity of matrix tablet. The matrix tablets with single drug were loaded either with propranolol hydrochloride or hydrochlorothiazide as hydrophilic and hydrophobic model drugs, and a dual drug formula was also prepared. The single and dual drug release patterns were studied in a dissolution apparatus using distilled water as medium. Propranolol hydrochloride released from matrix was easier than hydrochlorothiazide. Drug release from shellac wax matrix could be enhanced by incorporation of Lutrol. However retardation of drug release from some matrix tablets was evident for the systems that could form dispersion in the dissolution medium. The gel network from high content of Lutrol was hexagonal which was a dense and more compact structure than the other structures found when low amounts of Lutrol were present in the formula. Therefore, the formulae with high content of Lutrol could prolong drug release more efficiently than those containing low content of Lutrol. Hence shellac wax matrix could modulate the drug release with the addition of Lutrol. Sustainable dual drug release was also obtained from these developed matrix tablets. Thus shellac wax-Lutrol component could be used as a potential matrix tablet prepared with fusion and molding technique with excellent controlled drug release. PMID:25767320

  4. Drug release characteristics from chitosan-alginate matrix tablets based on the theory of self-assembled film.

    PubMed

    Li, Liang; Wang, Linlin; Shao, Yang; Ni, Rui; Zhang, Tingting; Mao, Shirui

    2013-06-25

    The aim of this study was to better understand the underlying drug release characteristics from chitosan-alginate matrix tablets containing different types of drugs. Theophylline, paracetamol, metformin hydrochloride and trimetazidine hydrochloride were used as model drugs exhibiting significantly different solubilities (12, 16, 346 and >1000 mg/ml at 37 °C in water). A novel concept raised was that drugs were released from chitosan-alginate matrix tablets based on the theory of a self-assembled film-controlled release system. The film was only formed on the surface of tablets in gastrointestinal environment and originated from chitosan-alginate polyelectrolyte complex, confirmed by differential scanning calorimetry characterization. The formed film could decrease the rate of polymer swelling to a degree, also greatly limit the erosion of tablets. Drugs were all released through diffusion in the hydrated matrix and polymer relaxation, irrespective of the drug solubility. The effects of polymer level and initial drug loading on release depended on drug properties. Drug release was influenced by the change of pH. In contrast, the impact of ionic strength of the release medium within the physiological range was negligible. Importantly, hydrodynamic conditions showed a key factor determining the superiority of the self-assembled film in controlling drug release compared with conventional matrix tablets. The new insight into chitosan-alginate matrix tablets can help to broaden the application of this type of dosage forms. PMID:23624081

  5. Role of various natural, synthetic and semi-synthetic polymers on drug release kinetics of losartan potassium oral controlled release tablets

    PubMed Central

    Jayasree, J.; Sivaneswari, S.; Hemalatha, G.; Preethi, N.; Mounika, B.; Murthy, S. Vasudeva

    2014-01-01

    Objective: The objective of the present work was to formulate and to characterize controlled release matrix tablets of losartan potassium in order to improve bioavailability and to minimize the frequency of administration and increase the patient compliance. Materials and Methods: Losartan potassium controlled release matrix tablets were prepared by direct compression technique by the use of different natural, synthetic and semisynthetic polymers such as gum copal, gum acacia, hydroxypropyl methyl cellulose K100 (HPMC K100), eudragit RL 100 and carboxy methyl ethyl cellulose (CMEC) individually and also in combination. Studies were carried out to study the influence of type of polymer on drug release rate. All the formulations were subjected to physiochemical characterization such as weight variation, hardness, thickness, friability, drug content, and swelling index. In vitro dissolution studies were carried out simulated gastric fluid (pH 1.2) for first 2 h and followed by simulated intestinal fluid (pH 6.8) up to 24 h, and obtained dissolution data were fitted to in vitro release kinetic equations in order to know the order of kinetics and mechanism of drug release. Results and Discussion: Results of physiochemical characterization of losartan potassium matrix tablets were within acceptable limits. Formulation containing HPMC K100 and CMEC achieved the desired drug release profile up to 24 h followed zero order kinetics, release pattern dominated by Korsmeyer — Peppas model and mechanism of drug release by nonfickian diffusion. The good correlation obtained from Hixson-Crowell model indicates that changes in surface area of the tablet also influences the drug release. Conclusion: Based on the results, losartan potassium controlled release matrix tablets prepared by employing HPMC K100 and CMEC can attain the desired drug release up to 24 h, which results in maintaining steady state concentration and improving bioavailability. PMID:25426439

  6. Sodium Deoxycholate Hydrogels: Effects of Modifications on Gelation, Drug Release, and Nanotemplating.

    PubMed

    McNeel, Kelsey E; Das, Susmita; Siraj, Noureen; Negulescu, Ioan I; Warner, Isiah M

    2015-07-01

    In the present study, sodium deoxycholate (NaDC) was used to produce gelation of tris(hydroxymethyl)amino-methane (TRIS) solutions above, below, and near the pKa of NaDC, respectively, which yielded a neutral gelator, a charged gelator, and a mixture of each. Impacts of ionic interactions on gel formation were studied in detail and showed that pH can be used to modify many hydrogel properties including sol-gel temperature, crystallinity, and mechanical strength. Several formulations yielded a unique rheological finding of two stable regions of elastic modulus. The release of a small molecule has been investigated under different hydrogel conditions and at variable shear rate, suggesting utility as a drug-delivery vehicle. It was also observed that pH modification of the hydrogels affected nanoparticle formation. Nanoparticles derived from a Group of Uniform Materials Based on Organic Salts (nanoGUMBOS), specifically cyanine-based NIR dyes, were templated within the hydrogel network for potential applications in tissue imaging. These nanoGUMBOS were found to be size-tunable, although material-dependent. Further understanding of NaDC/TRIS gelation has broadened the tunability and multidimensional applications of these tailored hydrogel systems. PMID:26039574

  7. Immediate release of poorly soluble drugs from starch-based pellets prepared via extrusion/spheronisation.

    PubMed

    Dukić-Ott, Aleksandra; Remon, Jean Paul; Foreman, Paul; Vervaet, Chris

    2007-11-01

    The aim of this study was to evaluate modified starch (high-amylose, crystalline and resistant starch) as the main excipient for immediate-release pellets containing poorly soluble drugs (hydrochlorothiazide and piroxicam) and prepared via extrusion/spheronisation. The bioavailability of pellets (containing 50 mg hydrochlorothiazide) was determined after oral administration to 6 dogs. A 2(4)-factorial design with central point was used to evaluate the influence of hydrochlorothiazide (10% and 50%, w/w), HPMC (binder, 4% and 7%, w/w), sorbitol (0% and 10%, w/w) and water (granulation liquid, low and high level) on pellet yield, size (Feret mean diameter) and sphericity (aspect ratio and two-dimensional shape factor, eR). Optimal granulation liquid content depended on drug and sorbitol level in the formulation. All factors except sorbitol content, as well as the interactions between drug concentration and binder level and between drug and water level, were significant (P<0.05) for pellet yield, while a significant curvature (P<0.05) suggested non-linearity of the response plots. The model was not significant for pellet shape, while hydrochlorothiazide and water level as well as their interaction were significant (P<0.05) for pellet size. Pellet friability, disintegration, residual water content and in-vitro drug release were determined. Pellets containing 2.5% (w/w) piroxicam were also evaluated. For both model drugs, pellets with a high yield (>90%), acceptable sphericity (AR<1.2) and low friability (<0.01%) were obtained. Due to pellet disintegration, fast dissolution of both hydrochlorothiazide and piroxicam was achieved: >80% drug released in 30 min. The bioavailability (AUC0-->24 h, Cmax and tmax) of hydrochlorothiazide pellets in dogs was not significantly different from fast-disintegrating immediate-release hydrochlorothiazide tablets (P>0.05). PMID:17537625

  8. High concentrations of drug in target tissues following local controlled release are utilized for both drug distribution and biologic effect: an example with epicardial inotropic drug delivery.

    PubMed

    Maslov, Mikhail Y; Edelman, Elazer R; Wei, Abraham E; Pezone, Matthew J; Lovich, Mark A

    2013-10-28

    Local drug delivery preferentially loads target tissues with a concentration gradient from the surface or point of release that tapers down to more distant sites. Drug that diffuses down this gradient must be in unbound form, but such drug can only elicit a biologic effect through receptor interactions. Drug excess loads tissues, increasing gradients and driving penetration, but with limited added biological response. We examined the hypothesis that local application reduces dramatically systemic circulating drug levels but leads to significantly higher tissue drug concentration than might be needed with systemic infusion in a rat model of local epicardial inotropic therapy. Epinephrine was infused systemically or released locally to the anterior wall of the heart using a novel polymeric platform that provides steady, sustained release over a range of precise doses. Epinephrine tissue concentration, upregulation of cAMP, and global left ventricular response were measured at equivalent doses and at doses equally effective in raising indices of contractility. The contractile stimulation by epinephrine was linked to drug tissue levels and commensurate cAMP upregulation for IV systemic infusion, but not with local epicardial delivery. Though cAMP was a powerful predictor of contractility with local application, tissue epinephrine levels were high and variable--only a small fraction of the deposited epinephrine was utilized in second messenger signaling and biologic effect. The remainder of deposited drug was likely used in diffusive transport and distribution. Systemic side effects were far more profound with IV infusion which, though it increased contractility, also induced tachycardia and loss of systemic vascular resistance, which were not seen with local application. Local epicardial inotropic delivery illustrates then a paradigm of how target tissues differentially handle and utilize drug compared to systemic infusion. PMID:23872515

  9. Effect of a new drug releasing system on microencapsulated islet transplantation

    PubMed Central

    Lu, Binjie; Gao, Qingkun; Liu, Rui; Ren, Ming; Wu, Yan; Jiang, Zaixing; Zhou, Yi

    2015-01-01

    Objective: This study aimed to develop a novel release system for grafted islets. Materials and methods: A graphene oxide-FTY720 release system was constructed to test the drug loading and releasing capacity. The recipient rats were divided into four groups as following: Experiment group A (EG A) and B (EG B); Control group A (CG A) and B (CG B). In each group, (2000±100) IEQ microencapsulated islets were implanted into the abdominal cavity of the recipients with oral FTY720, local graphene oxide-FTY720 injection, without immunosuppressants, and with graphene oxide-saturated solution respectively. We detected the immunological data, the blood glucose level, and pericapsular overgrowth to show the transplantation effect. Results: 31% of adsorptive FTY720 was released within 6 h, and 82% of FTY720 was released within 48 h. From day 5 to 8, the amount of PBL in EG B was significantly less than those in EG A (P<0.01). The CD3+ and CD8+ T lymphocytes were suppressed 3 days longer in EG B than in EG A. On day 19 posttransplantation, the blood glucose level in EG B was much lower than that in EG A (P<0.01). On the same day, pericapsular overgrowth was grade I in EG B, grade II in other groups. Conclusions: Graphene oxide-FTY720 complex showed a drug releasing effect. Local application of graphene-FTY720 releasing system could decrease the amount of peripheral blood lymphocytes (PBL) and the percentage of CD3 and CD8 T lymphocytes in blood for longer time than oral drug application. This releasing system could achieve a better blood glucose control. PMID:26722425

  10. Drug release mechanisms of chemically cross-linked albumin microparticles: effect of the matrix erosion.

    PubMed

    Sitta, Danielly L A; Guilherme, Marcos R; da Silva, Elisangela P; Valente, Artur J M; Muniz, Edvani C; Rubira, Adley F

    2014-10-01

    Albumin (BSA) microparticles were developed as a biotechnological alternative for drug delivery. Vitamin B12 (Vit-B12) was used as a model drug. The microparticles were obtained from maleic anhydride-functionalized BSA and N',N'-dimethylacrylamide (DMAAm) in a W/O emulsion without and with PVA. The microparticles produced at 15min of stirring without PVA showed the best results in terms of size, homogeneity, and sphericity. In such a case, BSA played a role as a surface active agent, replacing PVA. For longer stirring times, BSA was unable to act as an emulsifier. These microparticles showed an uncommon release profile, consisting of a two-step release mechanism, at the pH range studied. Considering that a two-step release mechanism is occurring, the experimental data were adjusted by applying modified power law and Weibull equations in order to describe release mechanism n and release rate constant k, respectively. Each one of the release stages was related to a specific value of n and k. The second stage was driven by a super case II transport mechanism, as a result of diffusion, macromolecular relaxation, and erosion. A third model, described by Hixson-Crowell, confirmed the erosion mechanism. Vit-B12 diffusion kinetics in aqueous solutions (i.e., without the microparticles) follows a one-step process, being k dependent on the pH, confirming that the two-step release mechanism is a characteristic profile of the developed microparticles. The microparticles released only 2.70% of their initial drug load at pH 2, and 58.53% at pH 10. PMID:25087021

  11. Drug release from E chemistry hypromellose tablets using the Bio-Dis USP type III apparatus: An evaluation of the effect of systematic agitation and ionic strength.

    PubMed

    Asare-Addo, Kofi; Supuk, Enes; Mahdi, Mohammed H; Adebisi, Adeola O; Nep, Elijah; Conway, Barbara R; Kaialy, Waseem; Al-Hamidi, Hiba; Nokhodchi, Ali

    2016-07-01

    The aim of the study was to evaluate the effect of systematic agitation, increasing ionic strength and gel strength on drug release from a gel-forming matrix (HPMC E10M, E4M and E50LV) using USP type III Bio-Dis apparatus with theophylline as a model drug. The triboelectric charging; particle sizing, water content, true density and SEM of all the hypromellose grades, theophylline and formulated blends were characterised. The results showed that balanced inter-particulate forces exist between drug particles and the excipient surface and this enabled optimum charge to mass ratio to be measured. Agitation and ionic strength affected drug release from E50LV and E4M tablet matrices in comparison to the E10M tablet matrices. Drug release increased substantially when water was used as the dissolution media relative to media at pH 1.2 (containing 0.4M NaCl). The results showed all f2 values for the E10M tablet matrices were above 50 suggesting the drug release from these tablet matrices to be similar. Rheological data also explained the different drug release behaviour with the stress required to yield/erode being 1Pa, 150Pa, and 320Pa, for the E50LV, E4M and E10M respectively. The stiffness of the gel was also found to be varied from 2.5Pa, 176.2Pa and 408.3Pa for the E50LV, E4M and E10M respectively. The lower G' value can be explained by a softer gel being formed after tablet introduction into the dissolution media thereby indicating faster drug release. PMID:27038913

  12. Effect of bioceramic functional groups on drug binding and release kinetics

    NASA Astrophysics Data System (ADS)

    Trujillo, Christopher

    Bioceramics have been studied extensively as drug delivery systems (DDS). Those studies have aimed to tailor the drug binding and release kinetics to successfully treat infections and other diseases. This research suggests that the drug binding and release kinetics are predominantly driven by the functional groups available on the surface of a bioceramic. The goal of the present study is to explain the role of silicate and phosphate functional groups in drug binding to and release kinetics from bioceramics. alpha-cristobalite (Cris; SiO2) particles (90-150 microm) were prepared and doped with 0 microg (P-0), 39.1 microg (P-39.1), 78.2 microg (P-78.2), 165.5 microg (P-165.5) or 331 microg (P-331) of P 2O5 per gram Cris, using 85% orthophosphoric (H3PO 4) acid and thermal treatment. The material structure was analyzed using X-ray diffraction (XRD) with Rietveld Refinement and Fourier Transform Infrared (FTIR) spectroscopy with Gaussian fitting. XRD demonstrated an increase from sample P-0 (170.5373 A3) to P-331 (170.6466 A 3) in the unit cell volume as the P2O5 concentration increased in the material confirming phosphate silicate substitution in Cris. Moreover, FTIR showed the characteristic bands of phosphate functional groups of nu4 PO4/O-P-O bending, P-O-P stretching, P-O-P bending, P=O stretching, and P-O-H bending in doped Cris indicating phosphate incorporation in the silicate structure. Furthermore, FTIR showed that the nu4 PO4/O-P-O bending band around 557.6 cm-1 and P=O stretching band around 1343.9 cm-1 increased in area for samples P-39.1 to P-331 from 3.5 to 10.5 and from 10.1 to 22.4, respectively due to phosphate doping. In conjunction with the increase of the nu4 PO4/O-P-O bending band and P=O stretching band, a decrease in area of the O-Si-O bending bands around 488.1 and 629.8 cm-1 was noticed for samples P-39.1 to P-331 from 5 to 2 and from 11.8 to 5.4, respectively. Furthermore, Cris samples (200 mg, n=5 for each sample) were immersed separately in

  13. Heat-Driven Release of a Drug Molecule From Carbon Nanotubes

    NASA Astrophysics Data System (ADS)

    Chaban, Vitaly; Prezhdo, Oleg

    2011-03-01

    Hydrophobicity and ability to absorb light that penetrates through living tissues make carbon nanotubes (CNTs) promising intracellular drug delivery agents. Following insertion of a drug molecule into a CNT, the latter is delivered into a tissue, is heated by near infrared radiation, and releases the drug. In order to assess the feasibility of this scheme, we investigate the rates of energy transfer between CNT, water and the drug molecule, and study the temperature and concentration dependence of the diffusion coefficient of the drug molecule inside CNTs. We use ciprofloxacin (CIP) as a sample drug: direct penetration of CIP through cell membranes is problematic due to its high polarity. The simulations show that a heated CNT rapidly deposits its energy to CIP and water. All estimated timescales for the vibrational energy exchange between CNT, CIP and water are less than 10 ps at 298 K. As the system temperature grows from 278 K to 363 K, the diffusion coefficient of the confined CIP increases 5-7 times, depending on CIP concentration. The diffusion coefficient slightly drops with increasing CIP concentration. This effect is more pronounced at higher temperatures. The simulations support the idea that optical heating of CNTs can assist in releasing encapsulated drugs.

  14. Coatless alginate pellets as sustained-release drug carrier for inflammatory bowel disease treatment.

    PubMed

    Md Ramli, Siti Hajar; Wong, Tin Wui; Naharudin, Idanawati; Bose, Anirbandeep

    2016-11-01

    Conventional alginate pellets underwent rapid drug dissolution and failed to exert colon targeting unless subjected to complex coating. This study designed coatless delayed-release oral colon-specific alginate pellets for ulcerative colitis treatment. Alginate pellets, formulated with water-insoluble ethylcellulose and various calcium salts, were prepared using solvent-free melt pelletization technique which prevented reaction between processing materials during agglomeration and allowed reaction to initiate only in dissolution. Combination of acid-soluble calcium carbonate and highly water-soluble calcium acetate did not impart colon-specific characteristics to pellets due to pore formation in fragmented matrices. Combination of moderately water-soluble calcium phosphate and calcium acetate delayed drug release due to rapid alginate crosslinking by soluble calcium from acetate salt followed by sustaining alginate crosslinking by calcium phosphate. The use of 1:3 ethylcellulose-to-alginate enhanced the sustained drug release attribute. The ethylcellulose was able to maintain the pellet integrity without calcium acetate. Using hydrophobic prednisolone as therapeutic, hydrophilic alginate pellets formulated with hydrophobic ethylcellulose and moderately polar calcium phosphate exhibited colon-specific in vitro drug release and in vivo anti-inflammatory action. Coatless oral colon-specific alginate pellets can be designed through optimal formulation with melt pelletization as the processing technology. PMID:27516284

  15. Modifying release characteristics from 3D printed drug-eluting products.

    PubMed

    Boetker, Johan; Water, Jorrit Jeroen; Aho, Johanna; Arnfast, Lærke; Bohr, Adam; Rantanen, Jukka

    2016-07-30

    This work describes an approach to modify the release of active compound from a 3D printed model drug product geometry intended for flexible dosing and precision medication. The production of novel polylactic acid and hydroxypropyl methylcellulose based feed materials containing nitrofurantoin for 3D printing purposes is demonstrated. Nitrofurantoin, Metolose® and polylactic acid were successfully co-extruded with up to 40% Metolose® content, and subsequently 3D printed into model disk geometries (ø10mm, h=2mm). Thermal analysis with differential scanning calorimetry and solid phase identification with Raman spectroscopy showed that nitrofurantoin remained in its original solid form during both hot-melt extrusion and subsequent 3D printing. Rheological measurements of the different compositions showed that the flow properties were sensitive to the amount of undissolved particles present in the formulation. Release of nitrofurantoin from the disks was dependent on Metolose® loading, with higher accumulated release observed for higher Metolose® loads. This work shows the potential of custom-made, drug loaded feed materials for 3D printing of precision drug products with tailored drug release characteristics. PMID:26987609

  16. Magnetic field activated drug release system based on magnetic PLGA microspheres for chemo-thermal therapy.

    PubMed

    Fang, Kun; Song, Lina; Gu, Zhuxiao; Yang, Fang; Zhang, Yu; Gu, Ning

    2015-12-01

    Controlled drug delivery systems have been extensively investigated for cancer therapy in order to obtain better specific targeting and therapeutic efficiency. Herein, we developed doxorubicin-loaded magnetic PLGA microspheres (DOX-MMS), in which DOX was encapsulated in the core and high contents (28.3 wt%) of γ-Fe2O3 nanoparticles (IOs) were electrostatically assembled on the surface of microsphere to ensure the high sensitivity to response of an external alternating current magnetic field (ACMF). The IOs in PLGA shell can both induce the heat effect and trigger shell permeability enhancement to release drugs when DOX-MMs was activated by ACMF. Results show that the cumulative drug release from DOX-MMs exposed to ACMF for 30 min (21.6%) was significantly higher (approximately 7 times higher) than that not exposed to ACMF (2.8%). The combination of hyperthermia and enhanced DOX release from DOX-MMS is beneficial for in vitro 4T1 breast cancer cell apoptosis as well as effective inhibition of tumor growth in 4T1 tumor xenografts. Therefore, the DOX-MMS can be optimized as powerful delivery system for efficient magnetic responsive drug release and chemo-thermal therapy. PMID:26513754

  17. Quantitative investigation, stability and in vitro release studies of anti-TB drugs in Triton niosomes.

    PubMed

    Mehta, Surinder K; Jindal, Neha; Kaur, Gurpreet

    2011-10-01

    The highly stable innocuous niosomes composed of four components (Triton X 100, polyethylene glycol 2000, water, Span 80) have been prepared successfully and characterized using particle size analyzer, transmission and scanning electron microscopy. The mean size has been found to be in the range 200-300 nm. The optimization of niosomes has been carried out using fluorescence spectroscopy. An attempt has been made to incorporate anti-tuberculosis drugs (ATD's) in the prepared niosomes. The stability and encapsulation efficiency of these drugs in the niosome have also been assessed and high encapsulation efficiency is observed. Such high encapsulation efficiency will serve as an advantage to solve the problem of multi-drug resistance in case of tuberculosis. Release studies and kinetics have been carried out to investigate the release behavior of drugs from the prepared niosomes. Fickian or diffusional release has been observed for rifampicin and isoniazid and a non-Fickian release mechanism for pyrazinamide. Fluorescence probe quenching technique has been used to determine the location and distribution coefficient of the ATD's in niosome/water system. PMID:21640561

  18. Sustained Drug Release on Temperature-Responsive Poly(N-isopropylacrylamide)-Integrated Hydroxyapatite

    SciTech Connect

    Shin, Yongsoon ); Liu, Jun; Chang, Jeong H.; Exarhos, Gregory J. )

    2002-01-01

    A hybrid temperature-responsive hydroxyapatite-poly(N-isopropylacrylamide) (HAP-PNIPAAm) gel has been synthesized by the interpenetration of PNIPAAm into a sintered HAP disk through a radical-initiated polymerization of NIPAAm monomers under N2 atmosphere, and shows sustained positive thermo-responsive drug release profile over a month at PBS buffer.

  19. Synthesis, characterization and drug release properties of 3D chitosan/clinoptilolite biocomposite cryogels.

    PubMed

    Dinu, Maria Valentina; Cocarta, Ana Irina; Dragan, Ecaterina Stela

    2016-11-20

    Three-dimensional (3D) biocomposites based on chitosan (CS) and clinoptilolite (CPL) were prepared by cryogelation and their potential application as drug carriers was investigated. Variation of CPL content from 0 to 33wt.% allowed the formation of biocomposites with heterogeneous morphologies consisting of randomly distributed pores. The further increase of CPL content led to ordered porous architectures where parallel pore channels were observed. The CPL content had a strong influence on water uptake, as well as on the cumulative release of diclofenac sodium (DS) and indomethacin (IDM). It was demonstrated that the drug delivery preferentially takes place in phosphate buffer saline (pH 7.4) in comparison to simulated gastric fluid (pH 1.2), where only a reduced drug release was observed. The drug release mechanism dominating these systems is described as a pseudo-Fickian diffusion, but it changes to non-Fickian release when 33wt.% of CPL was entrapped into the CS matrix or when IDM was loaded into biocomposites. PMID:27561488

  20. Chitosan-graft-beta-cyclodextrin scaffolds with controlled drug release capability for tissue engineering applications.

    PubMed

    Prabaharan, M; Jayakumar, R

    2009-05-01

    Biodegradable scaffolds composed of chitosan-g-beta-cyclodextrin (chit-g-beta-CD) were prepared by freeze-drying method as synthetic extracellular matrices to fill the gap during the healing process. Due to the presence of beta-CD, these scaffolds can be used as a matrix for drug loading and controlled release. The morphology, swelling and drug release properties of the scaffolds were found to be dependent on the extent of cross-linking density in the scaffolds. The drug dissolution profile showed that chit-g-beta-CD scaffolds provided a slower release of the entrapped ketoprofen than chitosan scaffold. The MTT assay showed that there is no obvious cytotoxicity of chit-g-beta-CD scaffolds cross-linked with 0.01 M of glutaraldehyde against the fibroblasts (L929) cells. These results suggest that chit-g-beta-CD scaffolds may become a potential biodegradable active filling material with controlled drug release capability, which provide a healthy environment and enhance the surrounding tissue regeneration. PMID:19428461

  1. Photon-Manipulated Drug Release from Mesoporous Nanocontainer Controlled by Azobenzene-Modified Nucleic Acid

    PubMed Central

    Yuan, Quan; Zhang, Yunfei; Chen, Tao; Lu, Danqing; Zhao, Zilong; Zhang, Xiaobing; Li, Zhenxing; Yan, Chun-Hua; Tan, Weihong

    2012-01-01

    Herein a photon manipulated mesoporous release system was constructed based on azobenzene-modified nucleic acids. In this system, the azobenzene-incorporated DNA double strands were immobilized at the pore mouth of meso-porous silica nanoparticles. The photo-isomerization of azobenzene induced dehybridization/hybridization switch of complementary DNA, causing uncapping/capping of pore gates of mesoporous silica. This nanoplatform permits holding of guest molecules within the nanopores under visible light but release them when light wavelength turns to UV range. These DNA/mesoporous silica hybrid nanostructures were exploited as carriers for cancer cell chemotherapy drug doxorubicin (DOX) due to its stimuli-responsive property as well as good biocompatibility via MTT assay. It is found that the drug release behavior is light wavelength sensitive. Switching of the light from visible to UV range uncapped the pores causes the release of DOX from the mesoporous silica nanospheres and an obvious cytotoxic effect on cancer cells. We envision that this photo-controlled drug release system could find potential applications in cancer therapy. PMID:22670595

  2. Layered double hydroxides as supports for intercalation and sustained release of antihypertensive drugs

    NASA Astrophysics Data System (ADS)

    Xia, Sheng-Jie; Ni, Zhe-Ming; Xu, Qian; Hu, Bao-Xiang; Hu, Jun

    2008-10-01

    Zn/Al layered double hydroxides (LDHs) were intercalated with the anionic antihypertensive drugs Enalpril, Lisinopril, Captopril and Ramipril by using coprecipitation or ion-exchange technique. TG-MS analyses suggested that the thermal stability of Ena -, Lis - (arranged with monolayer, resulted from X-ray diffraction (XRD) and Fourier transform infrared spectra (FT-IR) analysis was enhanced much more than Cap - and Ram - (arranged with bilayer). The release studies show that the release rate of all samples markedly decreased in both pH 4.25 and 7.45. However, the release time of Ena -, Lis - were much longer compared with Cap -, Ram - in both pH 4.25 and 7.45, it is possible that the intercalated guests, arranged with monolayer in the interlayer, show lesser repulsive force and strong affinity with the LDH layers. And the release data followed both the Higuchi-square-root law and the first-order equation well. Based on the analysis of batch release, intercalated structural models as well as the TG-DTA results, we conclude that for drug-LDH, stronger the affinity between intercalated anions and the layers is, better the thermal property and the stability to the acid attack of drug-LDH, and the intercalated anions are easier apt to monolayer arrangement within the interlayer, were presented.

  3. Genetic polymorphisms affect efficacy and adverse drug reactions of DMARDs in rheumatoid arthritis.

    PubMed

    Zhang, Ling Ling; Yang, Sen; Wei, Wei; Zhang, Xue Jun

    2014-11-01

    Disease-modifying antirheumatic drugs (DMARDs) and biological agents are critical in preventing the severe complications of rheumatoid arthritis (RA). However, the outcome of treatment with these drugs in RA patients is quite variable and unpredictable. Drug-metabolizing enzymes (dihydrofolate reductase, cytochrome P450 enzymes, N-acetyltransferases, etc.), drug transporters (ATP-binding cassette transporters), and drug targets (tumor necrosis factor-α receptors) are coded for by variant alleles. These gene polymorphisms may influence the pharmacokinetics, pharmacodynamics, and side effects of medicines. The cause for differences in efficacy and adverse drug reactions may be genetic variation in drug metabolism among individuals. Polymorphisms in drug transporter genes may change the distribution and excretion of medicines, and the sensitivity of the targets to drugs is strongly influenced by genetic variations. In this article, we review the genetic polymorphisms that affect the efficacy of DMARDs or the occurrence of adverse drug reactions associated with DMARDs in RA. PMID:25144752

  4. Desflurane differentially affects the release of proinflammatory cytokines in plasma and bronchoalveolar fluid of endotoxemic rats.

    PubMed

    Boost, Kim A; Hofstetter, Christian; Flondor, Michael; Betz, Christian; Homann, Markus; Pfeilschifter, Josef; Muehl, Heiko; Zwissler, Bernhard

    2006-06-01

    Previous studies have indicated that volatile anaesthetics can attenuate the inflammatory response to lipopolysaccharide (LPS) and other proinflammatory stimuli in vitro and in vivo. Thus far, no studies are available on the influences of desflurane on the cytokine-release. We therefore aimed to investigate the effects of desflurane on the systemic and pulmonary release of proinflammatory cytokines in endotoxemic rats. Eighteen anaesthetized and ventilated Sprague-Dawley rats were randomly assigned to the following groups: LPS-only: Six animals received LPS (5 mg/kg, i.v.) with no further intervention. LPS-Desflurane: Six animals received continuous inhalation of 1MAC Desflurane before and during endotoxemia with LPS (5 mg/kg, i.v.). Sham: Six animals served as control without inhalation of desflurane and endotoxemia. After 4 h, levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) in plasma and bronchoalveolar fluid were analyzed. Nitrite production as a readout for nitric oxide (NO) release from alveolar macrophages was measured by Griess assay. IkappaB-alpha degradation and iNOS-protein in macrophage homogenates were determined by Western Blotting. Inhalation of desflurane during endotoxemia showed a significant decrease in release of the proinflammatory cytokines TNF-alpha (-61%, P< or =0.05) and IL-1beta (-47%, P< or =0.05) in plasma as compared to LPS-only group, whereas the release of IL-6 was not significantly affected by desflurane. Within the lung, the NO-release was notably increased in supernatants of cultured alveolar macrophages from desflurane-group compared to both LPS-only and Sham group. IkappaB-alpha degradation in alveolar macrophages was impaired in the Desflurane-group as compared to the LPS-only group. Our data implicate that inhalation of 1MAC Desflurane during experimental endotoxemia differentially affects the inflammatory response in rats. PMID:16685427

  5. Copper ion-mediated liposomal encapsulation of mitoxantrone: the role of anions in drug loading, retention and release.

    PubMed

    Li, Chunlei; Cui, Jingxia; Li, Yingui; Wang, Caixia; Li, Yanhui; Zhang, Lan; Zhang, Li; Guo, Wenmin; Wang, Jinxu; Zhang, Hongwu; Hao, Yanli; Wang, Yongli

    2008-08-01

    Besides pH gradient, other transmembrane gradients such as metal ion gradient could be also employed to load drugs into liposomes. In pH gradient method, anions have an important role since they could form specific aggregates with drugs, and then affect drug release kinetics from vesicles. To explore the role of anions in metal ion gradient method, copper ion-mediated mitoxantrone (MIT) loading was investigated systematically. When empty liposomes exhibiting a transmembrane copper ion gradient (300 mM) were mixed with MIT in a molar ratio of 0.2:1, after 5 min incubation at 60 degrees C, >95% MIT could be loaded into vesicles and the encapsulation was stable, regardless of the kinds of anions and initial intraliposomal pH values. The encapsulation ratio decreased with increased MIT/lipid molar ratio. But even when the molar ratio increased to 0.4, >90% encapsulation could still be achieved. In the presence of nigericin and ammonium, the drug loading profiles were affected to different degree with respect to both drug loading rate and encapsulation ratio. Relative to CuSO(4)-containing systems, CuCl(2) mediated MIT loading was unstable. Both nigericin and ammonium could alter the absorption spectra of liposomal MITs loaded with CuSO(4) gradient. In vitro release studies were performed in glucose/histidine buffer and in 50% human plasma using a dialysis method. In both of release media, CuCl(2)-containing vesicles displayed rapid release kinetics in comparison with CuSO(4) systems; and during the experiment period, MIT was lost from the vesicles continuously. When the formulations were injected into BDF1 mice at a dose of 4 mg/kg, all the liposomal formulations exhibited enhanced blood circulation time, with half-life values of 6.8-7.2h, significantly compared to the rapid clearance of free-MIT. In L1210 ascitic model, CuCl(2) formulation was more therapeutically active than CuSO(4) formulation. At a dose of 6 mg/kg, the treatment with CuCl(2) formulation resulted in

  6. The release dynamics of model drugs from the psyllium and N-hydroxymethylacrylamide based hydrogels.

    PubMed

    Singh, Baljit; Chauhan, G S; Sharma, D K; Kant, Anil; Gupta, I; Chauhan, Nirmala

    2006-11-15

    In order to utilize the psyllium husk, a medicinally important natural polysaccharide, for developing the novel hydrogels for the controlled drug delivery device, we have prepared psyllium and N-hydroxymethylacrylamide based polymeric networks by using N,N'-methylenebisacrylamide (N,N'-MBAAm) as crosslinker. The polymeric networks thus formed were characterized with scanning electron micrography (SEM), FTIR and thermogravimetric analysis (TGA) techniques to study various structural aspects of the networks and also with the swelling response of the polymeric networks as a function of time, temperature, pH and [NaCl]. Equilibrium swelling has been observed to depend on both structural aspects of the polymers and environmental factors. Maximum P(s) 748.3 was observed at 13.0 x 10(-3)mol/L of [N,N'-MBAAm] in 0.5M NaOH solution. The release dynamics of model drugs (salicylic acid and tetracycline hydrochloride) from hydrogels has also been discussed, for the evaluation of the release mechanism and diffusion coefficients. The effect of pH on the release pattern of tetracycline has been studied by varying the pH of the release medium. In release medium of pH 7.4 buffer the release pattern of tetracycline drastically changes to the extent that mechanism of drug diffusion shifted from non-Fickian diffusion to Fickian diffusion. It has been observed that diffusion exponent "n" have 0.71, 0.67 and 0.52 values and gel characteristic constant 'k' have 1.552 x 10(-2), 2.291 x 10(-2) and 5.309 x 10(-2) values in distilled water, pH 2.2 buffer and pH 7.4 buffer, respectively, for tetracycline release. In solution of pH 7.4 buffer, the rate of polymer chain relaxation was more as compare to the rate of drug diffusion from these hydrogels and it follows Fick's law of diffusion. The value of the initial diffusion coefficient for the release of tetracycline hydrochloride was higher than the value of late time diffusion coefficient in each release medium indicating that in the start

  7. Setting radon-specific release criteria and demonstrating compliance for land affected by NORM.

    PubMed

    García-Talavera, M; Martínez, M; Matarranz, J L M; Ramos, L

    2008-11-01

    Residues from industrial activities involving naturally occurring radioactive materials (NORMs) may cause radiation exposures to members of the public, particularly when NORM-affected land is brought into residential use. To provide an adequate protection against radiation in such situations, the following limiting criteria are currently required in Spain for releasing NORM-affected land: (i) no more than a 300 microSv yr(-1) increase (excluding radon doses) over the natural background; (ii) (222)Rn concentrations in hypothetical future dwellings lower than 200 Bq m(-3); and (iii) reduction of all radiation exposures to as low as reasonable achievable. This paper addresses some of the problems encountered in translating the (222)Rn criterion into site-specific release limits and in demonstrating compliance with them. PMID:18508275

  8. Diffusion Processes and Drug Release: Capsaicinoids - Loaded Poly (ε-caprolactone) Microparticles

    PubMed Central

    Lenzi, E. K.; Novatski, A.; Farago, P. V.; Almeida, M. A.; Zawadzki, S. F.; Menechini Neto, R.

    2016-01-01

    We present a generalmodel based on fractional diffusion equation coupled with a kinetic equation through the boundary condition. It covers several scenarios that may be characterized by usual or anomalous diffusion or present relaxation processes on the surface with non-Debye characteristics. A particular case of this model is used to investigate the experimental data obtained from the drug release of the capsaicinoids-loaded Poly (ε-caprolactone) microparticles. These considerations lead us to a good agreement with experimental data and to the conjecture that the burst effect, i.e., an initial large bolus of drug is released before the release rate reaches a stable profile, may be related to an anomalous diffusion manifested by the system. PMID:27309358

  9. Multi-responsive magnetic microsphere of poly(N-isopropylacrylamide)/carboxymethylchitosan hydrogel for drug controlled release.

    PubMed

    Rodkate, Nantharak; Rutnakornpituk, Metha

    2016-10-20

    Multi-responsive composite microspheres were synthesized via an in situ free radical polymerization of thermo-responsive poly(N-isopropylacrylamide) (poly(NIPAAm)) in the presence of carboxymethylchitosan (CMC) and magnetite nanoparticles (MNPs) followed by glutaraldehyde crosslinking. Formulation conditions of the composite microspheres were tuned such that spherical microspheres with narrow size distributions were obtained (30.0±1.0μm in diameter). They responded well to an applied magnetic field and showed water swelling responses to the change in solution pH and temperature. The release of an entrapped indomethacin model drug was accelerated when the solution temperature was above its lower critical solution temperature (LCST) (50°C) or when the solution pH was in basic conditions (pH 11). These responsive properties can be used as triggering mechanisms for releases of the entrapped drugs from the microspheres, indicating their great potentials for use in controlled release applications. PMID:27474565

  10. Endogenous Progesterone Concentrations Affect Progesterone Release from Intravaginal Devices Used for Oestrous Synchronization in Cattle.

    PubMed

    Neri, H L; Palhao, M P; Costa, D S; Viana, Jhm; Fernandes, Cac

    2015-08-01

    Intravaginal progesterone-releasing devices are largely used both as contraceptives in humans and as a component of oestrous synchronization protocols in cattle. To reduce costs in large-scale timed artificial insemination, the reuse of these releasing devices is common. Passive hormone diffusion, however, depends on the concentration gradient, which could affect the amount of residual progesterone present in these devices after a first use. To evaluate the effect of the presence of a corpus luteum in the release of progesterone from intravaginal devices, three synchronization protocols were designed to simulate the effects of inserting the device in the early dioestrus, late dioestrus or anoestrus. Holstein-Zebu cross-bred heifers were randomly allocated into one of these three treatments, and a series of blood samples was taken to evaluate the plasma progesterone concentrations. After 8 days, the intravaginal devices were removed and underwent a previously validated alcoholic extraction technique to measure the residual progesterone. Non-used devices were used as controls. As expected, the simultaneous presence of the intravaginal device and a corpus luteum resulted in increased plasma progesterone concentrations. Conversely, the amount of residual progesterone in the devices after use was inversely proportional to the plasma progesterone concentration. These results demonstrate that the release rate of progesterone from intravaginal devices is affected by the endogenous concentration of this hormone; consequently, the strategy for reuse should account for the category and expected luteal cyclic activity of the animals undergoing synchronization protocols. PMID:26059020

  11. Preparation and drug release properties of norisoboldine-loaded chitosan microspheres.

    PubMed

    He, Miao; Wang, Haiyan; Dou, Wei; Chou, Guixin; Wei, Xiaohui; Wang, Zhengtao

    2016-10-01

    This study aimed to develop injectable norisoboldine (NOR) chitosan microspheres formulated through the emulsion cross-linking method. The formulation was optimized using response surface methodology (RSM) with a three-level, three-factor Box-Behnken design (BBD). The morphology, size, physicochemical characterization and in vitro release behavior of the optimized formulation were evaluated. Scanning electron micrographs (SEM) indicated that the microspheres were spherical with a smooth surface. The encapsulation efficiency and drug loading content of the microspheres were 38.89%±1.72% and 4.25%±0.15%, respectively, with an average size of 105μm. Fourier-transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC) and X-ray diffraction (XRD) revealed the absence of a drug-polymer interaction and the amorphous nature of an entrapped drug. Analysis results of drug release in vitro show the burst release of the microsphere in 2h and a slow progression afterward. In vivo studies using Sprague-Dawley rats revealed that the NOR-loaded chitosan microspheres were biocompatible. This study suggests that the BBD with desired formulation could provide a suitable drug delivery system of chitosan microspheres. PMID:27344949

  12. Controlled release of anti-diabetic drug Gliclazide from poly(caprolactone)/poly(acrylic acid) hydrogels.

    PubMed

    Bajpai, S K; Chand, Navin; Soni, Shweta

    2015-01-01

    Drug Gliclazide (Glz) has limited solubility and low bioavailability. In order to obtain a controlled release of this drug and to improve its bioavailability, the drug has been loaded into poly(caprolactone) (PCL)/poly(acrylic acid) (PAAc) hydrogels, prepared by free radical polymerization of acrylic acid in the presence of poly(caprolactone) in acetone medium using azo-isobutyronitrile as initiator and N,N' methylene bisacrylamide as cross-linking agent. The swelling behaviour of these hydrogels has been investigated in the physiological gastric and intestinal fluids to obtain an optimum composition suitable for delivery of a biologically active compound. The gels were loaded with anti-diabetic drug Glz and a detailed investigation of release of drug has been carried out. Various kinetic models have been applied on the release data. Finally, the Albino wistar rats were treated for Streptozotocin plus nicotinamide - induced diabetes using a Glz-loaded PCL/PAAc hydrogel. The results indicated a fair reduction in the glucose level of rats. PMID:26135033

  13. Polypyrrole Film as a Drug Delivery System for the Controlled Release of Risperidone

    NASA Astrophysics Data System (ADS)

    Svirskis, Darren; Travas-Sejdic, Jadranka; Rodgers, Anthony; Garg, Sanjay

    2009-07-01

    Conducting polymers are finding applications in medicine including drug delivery systems, biosensors and templates for the regeneration of nervous pathways. We aim to develop a novel system where the drug release rate can be controlled by electrical stimulation. Polypyrrole (PPY) is being used as a drug delivery system due to its inherent electrical conductivity, ease of preparation and apparent biocompatibility. Risperidone is an atypical antipsychotic drug used in the treatment of psychosis and related disorders, including schizophrenia. PPY was synthesised using p-toluene sulfonic acid as a primary dopant, in the presence of risperidone. A validated high performance liquid chromatography (HPLC) analytical method was used to quantify risperidone release. It has been demonstrated that the release rate of risperidone can be altered through the application, or absence, of electrical stimulation. Technology such as this would find use in drug-delivering implants where the dose could be adjusted through application of external stimulus, optimising benefit to side effect ratio, while simultaneously ensuring patient adherence (which is a particular challenge in mental health conditions).

  14. Hollow polycaprolactone composite fibers for controlled magnetic responsive antifungal drug release.

    PubMed

    Wang, Baolin; Zheng, Hongxia; Chang, Ming-Wei; Ahmad, Zeeshan; Li, Jing-Song

    2016-09-01

    Hollow magnetic fibers for trigger based drug release were synthesized using one-step co-axial electrospinning (COX-ES). This was achieved by encapsulating the antifungal active 'ketoconazole' (KCZ) and iron oxide (Fe3O4) nanoparticles (NPs) in composite form within the core shell polymeric matrix material (polycaprolactone, PCL) during the COX-ES process. Dimethyl silicone oil was used as the inner core (liquid) of co-flowing solutions, which subsequently perfused out of the two-phase electrospun microstructures to form hollow fibers. Resulting drug-loaded magnetic hollow fibers were characterized using optical microscopy, scanning electron microscopy and Fourier Transform Infra-Red. The tensile strength and magnetization properties of composite fibers were also assessed. KCZ drug concentration in electrospinning solutions strongly influenced resulting fiber morphology, drug loading efficiency and release. Expedited drug release during a slow-sustained phase was demonstrated through the application of an auxiliary magnetic field. Variations in tensile strength (∼1.3-6.3MPa) were due to composite fiber components compromising polymer chain integrity. In-vitro cell studies (using human cervical carcinoma cell lines) demonstrated fiber biocompatibility. The present study demonstrates the potential application of magnetic hollow fibers for controlled treatment of fungal infections and antimicrobial indications. PMID:27295492

  15. Drug release and permeation studies of nanosuspensions based on solidified reverse micellar solutions (SRMS).

    PubMed

    Friedrich, I; Reichl, S; Müller-Goymann, C C

    2005-11-23

    Solidified reverse micellar solutions (SRMS), i.e. mixtures of lecithin and triglycerides, offer high solubilisation capacities for different types of drugs in contrast to simple triglyceride systems [Friedrich, I., Müller-Goymann, C.C., 2003. Characterisation of SRMS and production development of SRMS-based nanosuspensions. Eur. J. Pharm. Biopharm. 56, 111-119]. Nanosuspensions based on SRMS were prepared by homogenisation close to the melting point of the SRMS matrix. In a first step the SRMS matrices of 1:1 (w/w) ratios of lecithin and triglycerides were loaded with 17beta-estradiol-hemihydrate (EST), hydrocortisone (HC) or pilocarpine base (PB), respectively, and subsequently ground in liquid nitrogen to minimise drug diffusion later on. The powder was then dispersed in a polysorbate 80 solution using high pressure homogenisation. The drug loading capacities of the nanosuspensions were very high in the case of poorly water-soluble EST (99% of total 0.1%, w/w, EST) and HC (97% of total 0.5%, w/w, HC) but not sufficient with the more hydrophilic PB (37-40% of total 1.0%, w/w, PB). These findings suggest SRMS-based nanosuspensions to be promising aqueous drug carrier systems for poorly soluble drugs like EST and HC. Furthermore, in vitro drug permeation from the different drug-loaded nanosuspensions was performed across human cornea construct (HCC) as an organotypical cell culture model. PB permeation did not differ from the nanosuspension and an aqueous solution whereas the permeation coefficients of HC-loaded nanosuspensions were reduced in comparison to aqueous and oily solutions of HC. However, the permeated amount was higher from the nanosuspensions due to a much lower HC concentration in the solution than that in the nanosuspension (solution 0.02%, w/w, versus nanosuspension 0.5%, w/w). The high drug load of the nanoparticles provides prolonged HC release. Permeated amounts of EST were reduced in comparison to HC and only detectable with an ELISA technique

  16. Effect of processing methods on drug release profiles of anti-restenotic self-assembled monolayers

    NASA Astrophysics Data System (ADS)

    Stoebner, Susan E.; Mani, Gopinath

    2012-04-01

    The use of anti-restenotic self-assembled monolayers (ARSAMs) has been previously demonstrated for delivering drugs from stents without polymeric carriers. ARSAMs have been prepared by coating an anti-restenotic drug (paclitaxel - PAT) on -COOH terminated phosphonic acid self-assembled monolayers (SAMs) coated Co-Cr alloy specimens. This study investigates the effect of different processing methods on the percentage of drug release from ARSAMs. The different methods that were used in this study to process ARSAMs include room temperature (RT) treatment, heat treatment (HT), cold treatment (CT) and quenching. The changes in polymorphism, chemical structure, morphology, and distribution of PAT on SAMs coated specimens were investigated using differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and atomic force microscopy (AFM), respectively. DSC showed dihydrate, dehydrated dihydrate, semi-crystalline, and mixed (amorphous and dihydrate) forms of PAT for RT, HT, CT, and quenched specimens, respectively. FTIR showed that the chemical structure of PAT was unaltered in all the specimens processed by various methods employed in this study. SEM showed a mixture of spherical, ovoid, and bean-shaped morphologies of PAT on RT, HT, and CT while particle-like and needle-shaped morphologies of PAT were observed on quenched specimens. AFM showed PAT was uniformly distributed on RT, HT and CT specimens while particle-like PAT was well distributed and needle-shaped PAT was sparsely distributed on quenched specimens. CT specimens showed greater density of PAT crystals when compared to other methods. Thus, this study demonstrated that processing methods have significant influence on the polymorphism, morphology, and distribution of PAT on SAMs coated Co-Cr alloy specimens. The in vitro drug elution studies for up to 56 days showed sustained release for all the different groups of specimens. CT showed lesser

  17. Drug Formulation Advances in Extended-Release Medications for Pain Control.

    PubMed

    Jones, Mark R; Carney, Martin J; Kaye, Rachel J; Prabhakar, Amit; Kaye, Alan D

    2016-06-01

    Prescription opioid abusers frequently tamper with opioid tablets in order to either accelerate the delivery of the euphoria-inducing agent or to alter the route of delivery, such that it may be delivered intranasally or intravenously. As one strategy to combat the opioid epidemic in the USA, drug manufacturers have begun to explore formulations which resist such tampering by abusers. Techniques to prevent tampering consist of physical barriers to crushing, chewing, and drug extraction, or aversive or antagonistic agents, incorporated within the formulation itself. Recent years have seen the development of numerous extended-release opioid agents, which are described in this review. This article provides a comprehensive summary of the pharmacology, benefits, risks, and processes behind the development of currently available extended-release opioid drugs, as well as a glimpse into promising future formulations. PMID:27084375

  18. Hierarchical porous bioactive glasses/PLGA-magnetic SBA-15 for dual-drug release.

    PubMed

    Ma, Jie; Lin, Huiming; Li, Xiaofeng; Bian, Chunhui; Xiang, Di; Han, Xiao; Wu, Xiaodan; Qu, Fengyu

    2014-06-01

    The hierarchical porous bioglass combined with magnetic SBA-15 was synthesized. The bioactive glass materials possess a hierarchical porous structure with the macroporous (50μm) and the mesoporous (3.86nm) structures derived from the plant template (cattail stem) and triblock polyethylene oxide-propylene oxide block copolymer (P123), respectively. Magnetic SBA-15 was synthesized by adopting the post assembly method using Fe(NO3)3 as iron source and ethylene glycol as reduction. After coating PLGA, PLGA-IBU-magnetic SBA-15 also possessed super-paramagnetism and the corresponding saturation magnetizations (Ms) could reach 2.6emug(-1). Metformin HCl (MH) and ibuprofen (IBU) were used as model drugs, and the drug release kinetics was studied. MH and IBU could release 60% and 85% from the sample respectively. The system shows excellent dual-drug controlled delivery performance and good bioactivity in vitro that leads to good potential application on bone regeneration. PMID:24863192

  19. Modelling irradiation by EM waves of multifunctionalized iron oxide nanoparticles and subsequent drug release

    NASA Astrophysics Data System (ADS)

    Wang, Feng; Calvayrac, Florent; Montembault, Véronique; Fontaine, Laurent

    2015-09-01

    Thermal transport in the environment close to the periphery of the nanoparticle, from a few angstroms to less than a nanometer scale, is becoming increasingly important with the advent of several biomedical applications of multifunctional magnetic nanoparticles, including drug delivery, magnetic resonance imaging, and hyperthermia therapy. We present a multiscale and multiphysics model of the irradiation by electromagnetic waves of radiofrequency of iron oxide nanoparticles functionalized by drug-releasing polymers used as new multifunctional therapeutic compounds against tumors. We compute ab initio the thermal conductivity of the polymer chains as a function of the length, model the unfolding of the polymer after heat transfer from the nanoparticle by molecular mechanics, and develop a multiscale thermodynamic and heat transfer model including the surrounding medium (water) in order to model the drug release.

  20. Improved Tumor-Specific Drug Accumulation by Polymer Therapeutics with pH-Sensitive Drug Release Overcomes Chemotherapy Resistance.

    PubMed

    Heinrich, Anne-Kathrin; Lucas, Henrike; Schindler, Lucie; Chytil, Petr; Etrych, Tomáš; Mäder, Karsten; Mueller, Thomas

    2016-05-01

    The success of chemotherapy is limited by poor selectivity of active drugs combined with occurrence of tumor resistance. New star-like structured N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-based drug delivery systems containing doxorubicin attached via a pH-sensitive hydrazone bond were designed and investigated for their ability to overcome chemotherapy resistance. These conjugates combine two strategies to achieve a high drug concentration selectively at the tumor site: (I) high accumulation by passive tumor targeting based on enhanced permeability and retention effect and (II) pH-sensitive site-specific drug release due to an acidic tumor microenvironment. Mice bearing doxorubicin-resistant xenograft tumors were treated with doxorubicin, PBS, poly HPMA (pHPMA) precursor or pHPMA-doxorubicin conjugate at different equivalent doses of 5 mg/kg bodyweight doxorubicin up to a 7-fold total dose using different treatment schedules. Intratumoral drug accumulation was analyzed by fluorescence imaging utilizing intrinsic fluorescence of doxorubicin. Free doxorubicin induced significant toxicity but hardly any tumor-inhibiting effects. Administering at least a 3-fold dose of pHPMA-doxorubicin conjugate was necessary to induce a transient response, whereas doses of about 5- to 6-fold induced strong regressions. Tumors completely disappeared in some cases. The onset of response was differential delayed depending on the tumor model, which could be ascribed to distinct characteristics of the microenvironment. Further fluorescence imaging-based analyses regarding underlying mechanisms of the delayed response revealed a related switch to a more supporting intratumoral microenvironment for effective drug release. In conclusion, the current study demonstrates that the concept of tumor site-restricted high-dose chemotherapy is able to overcome therapy resistance. Mol Cancer Ther; 15(5); 998-1007. ©2016 AACR. PMID:26939698

  1. Drug complexation, in vitro release and cellular entry of dendrimers and hyperbranched polymers.

    PubMed

    Kolhe, Parag; Misra, Ekta; Kannan, Rangaramanujam M; Kannan, Sujatha; Lieh-Lai, Mary

    2003-06-18

    Highly branched, functionalized polymers have potential to act as efficient drug carrier systems. Dendrimers are ideal candidates among model hyperbranched polymers because of their well-defined structure and high density of functional groups. Using ibuprofen as a model drug, we studied the interaction between the drug and Polyamidoamine (PAMAM) dendrimers (generations 3 and 4 with --NH2 functionality) and Perstrop Polyol (generation 5, hyperbranched polyester with --OH functionality). FTIR and NMR studies suggest that ibuprofen predominantly forms a complex with PAMAM dendrimers because of the ionic interaction between the --NH2 end groups and the carboxyl group of ibuprofen. On an average, up to 78 molecules of ibuprofen could be incorporated into one molecule of PAMAM-G4-NH2 with 64 end groups. This complex is stable in deionized water and methanol. The in vitro release of ibuprofen from drug-dendrimer complex is appreciably slower compared to pure ibuprofen. The complexed drug enters A549 cells much more rapidly than pure drug suggesting that dendrimers may be able to carry the complexed drug inside cells efficiently. Hyperbranched Polyol (with 128 --OH end groups) appears to encapsulate approximately 24 drug molecules. Perhaps the lack of strong interactions between the --OH end groups and the drugs prevents complex formation. PMID:12787643

  2. Community reentry challenges after release from prison among people who inject drugs in St. Petersburg, Russia

    PubMed Central

    Cepeda, Javier A.; Vetrova, Marina V.; Lyubimova, Alexandra I.; Levina, Olga S.; Heimer, Robert; Niccolai, Linda M.

    2016-01-01

    Purpose Little is known about the context of the post-release risk environment among formerly incarcerated people who inject drugs (PWID) in Russia. The purpose of this paper is to explore these challenges as they relate to reentry, relapse to injection opioid use, and overdose. Design/methodology/approach The authors conducted 25 in-depth semi-structured interviews among PWID living in St Petersburg, Russia who had been incarcerated within the past two years. Participants were recruited from street outreach (n = 20) and a drug treatment center (n = 5). Findings Emergent themes related to the post-release environment included financial instability, negative interactions with police, return to a drug using community, and reuniting with drug using peers. Many respondents relapsed to opioid use immediately after release. Those whose relapse occurred weeks or months after their release expressed more motivation to resist. Alcohol or stimulant use often preceded the opioid relapse episode. Among those who overdosed, alcohol use was often reported prior to overdosing on opioids. Practical implications Future post-release interventions in Russia should effectively link PWID to social, medical, and harm reduction services. Particular attention should be focussed on helping former inmates find employment and overdose prevention training prior to leaving prison that should also cover the heightened risk of concomitant alcohol use. Originality/value In addition to describing a syndemic involving the intersection of incarceration, injection drug use, poverty, and alcohol abuse, the findings can inform future interventions to address these interrelated public health challenges within the Russian setting. PMID:26277925

  3. Redox and pH-responsive degradable micelles for dually activated intracellular anticancer drug release.

    PubMed

    Chen, Wei; Zhong, Ping; Meng, Fenghua; Cheng, Ru; Deng, Chao; Feijen, Jan; Zhong, Zhiyuan

    2013-08-10

    Redox and pH dual-responsive biodegradable micelles were developed based on poly(ethylene glycol)-SS-poly(2,4,6-trimethoxybenzylidene-pentaerythritol carbonate) (PEG-SS-PTMBPEC) copolymer and investigated for intracellular doxorubicin (DOX) release. PEG-SS-PTMBPEC copolymer with an Mn of 5.0-4.1kg/mol formed micellar particles with an average diameter of 140nm and a low polydispersity of 0.12. DOX was loaded into PEG-SS-PTMBPEC micelles with a decent drug loading content of 11.3wt.%. The in vitro release studies showed that under physiological conditions only ca. 24.5% DOX was released from DOX-loaded micelles in 21h. The release of DOX was significantly accelerated at pH5.0 or in the presence of 10mM glutathione (GSH) at pH7.4, in which 62.8% and 74.3% of DOX was released, respectively, in 21h. The drug release was further boosted under 10mM GSH and pH 5.0 conditions, with 94.2% of DOX released in 10h. Notably, DOX release was also facilitated by 2 or 4h incubation at pH 5.0 and then at pH 7.4 with 10mM GSH, which mimics the intracellular pathways of endocytosed micellar drugs. Confocal microscopy observation indicated that DOX was delivered and released into the nuclei of HeLa cells following 8h incubation with DOX-loaded PEG-SS-PTMBPEC micelles, while DOX was mainly located in the cytoplasm for reduction-insensitive PEG-PTMBPEC controls. MTT assays revealed that DOX-loaded PEG-SS-PTMBPEC micelles had higher anti-tumor activity than reduction-insensitive controls, with low IC50 of 0.75 and 0.60μg/mL for HeLa and RAW 264.7 cells, respectively, following 48h incubation. PEG-SS-PTMBPEC micelles displayed low cytotoxicity up to a concentration of 1.0mg/mL. These redox and pH dual-bioresponsive degradable micelles have appeared as a promising platform for targeted intracellular anticancer drug release. PMID:23306022

  4. Aptamer/Graphene Quantum Dots Nanocomposite Capped Fluorescent Mesoporous Silica Nanoparticles for Intracellular Drug Delivery and Real-Time Monitoring of Drug Release.

    PubMed

    Zheng, Fen-Fen; Zhang, Peng-Hui; Xi, Yu; Chen, Jing-Jia; Li, Ling-Ling; Zhu, Jun-Jie

    2015-12-01

    Great challenges in investigating the release of drug in complex cellular microenvironments necessitate the development of stimuli-responsive drug delivery systems with real-time monitoring capability. In this work, a smart drug nanocarrier based on fluorescence resonance energy transfer (FRET) is fabricated by capping graphene quantum dots (GQDs, the acceptor) onto fluorescent mesoporous silica nanoparticles (FMSNs, the donor) via ATP aptamer for real-time monitoring of ATP-triggered drug release. Under extracellular conditions, the fluorescence of FMSNs remains in the "off" state in the low ATP level which is unable to trigger the release of drug. Once specifically recognized and internalized into the target tumor cells by AS1411 aptamer, in the ATP-rich cytoplasm, the conformation switch of the ATP aptamer causes the shedding of the GQDs from the nanocarriers, leading to the release of the loaded drugs and consequently severe cytotoxicity. Simultaneously, the fluorescence of FMSNs turns "on" along with the dissociation of GQDs, which allows real-time monitoring of the release of drug from the pores. Such a drug delivery system features high specificity of dual-target recognition with AS1411 and ATP aptamer as well as high sensitivity of the FRET-based monitoring strategy. Thus, the proposed multifunctional ATP triggered FRET-nanocarriers will find potential applications for versatile drug-release monitoring, efficient drug transport, and targeted cancer therapeutics. PMID:26524192

  5. Synthesis of Depo-Medrol-chitosan hydrogel as new drug slow-release appliance and investigation of release kinetics by high-performance liquid chromatography.

    PubMed

    Alizadeh, Reza; Jabbari, Sara Majd; Zarnani, Amir H; Barghi, Hamidreza

    2016-09-01

    The present study deals with preparation and optimization of a novel chitosan hydrogel-based matrix by suspension cross-linking method for controlled release of Depo-Medrol. The controlled release of Depo-Medrol for effective Rheumatoid arthritis disease has become an imperative field in the drug delivery system. In this context, it was intended to optimize loading circumstances by experimental design and also study the release kinetics of Depo-Medrol entrapped in the chitosan matrix in order to obtain maximal efficiency for drug loading. The optimum concentrations of chitosan (2.5 g), glutaraldehyde (3.05 μL) and Depo-Medrol (0.1 mg) were set up to achieve the highest value of drug loaded and the most sustained release from the chitosan matrix. In vitro monitoring of drug release kinetic using high-performance liquid chromatography showed that 73% of the Depo-Medrol was released within 120 min, whereas remained drug was released during the next 67 h. High correlation between first-order and Higuchi's kinetic models indicates a controlled diffusion of Depo-Medrol through the surrounding media. Moreover, recovery capacity >82% and entrapment efficiency of 58-88% were achieved under optimal conditions. Therefore, the new synthesized Depo Medrol-chitosan is an applicable appliance for arthritis therapy by slow release mechanism. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26713406

  6. Polysaccharides based superabsorbent hydrogel from Linseed: Dynamic swelling, stimuli responsive on-off switching and drug release.

    PubMed

    Haseeb, Muhammad T; Hussain, Muhammad A; Yuk, Soon H; Bashir, Sajid; Nauman, Muhammad

    2016-01-20

    Swelling properties of Linseed hydrogel (LSH) were studied in deionized water and different physiological pH values, i.e., 1.2, 6.8 and 7.4. Analysis of the kinetics drawn from swelling data has revealed that swelling of LSH followed second order kinetics. The results indicated that swelling of LSH is greatly affected by different concentration of salts. Stimuli responsive on-off switching of LSH was studied in water/normal saline, water/ethanol and basic/acidic environment and found reversible. LSH swells maximum in water and at pH 7.4 while deswells abruptly in ethanol and at pH 1.2. The elongated porous structures uniformly organized in layers were observed in FE-SEM. LSH was used as a sustained release material for tablet formulation of diclofenac sodium. Drug release study followed non-Fickian diffusion. LSH sustained the release of drug even better than a commercially available formulation of diclofenac sodium. PMID:26572409

  7. Water soluble drug releasing soft contact lens in response to pH of tears

    NASA Astrophysics Data System (ADS)

    Kim, G.; Noh, H.

    2016-06-01

    Human tear characteristics including pH and compositions can vary significantly depending on physical and environmental factors. Contact lenses directly contact with human tears can be swelled or de-swelled depending on the pH of the solution due to the nature of the hydrogel. For examples, anionic hydrogels, when the solution's pH is low, is shrunken due to the electric attraction force within the hydrogel network; the opposite phenomenon appears when the solution is basic. The purpose of this study was to evaluate the extent of water soluble drug, hydroxyl propyl methyl cellulose, released from contact lens according to the pH of the artificial tears. Artificial tears are prepared by mixing lysozyme, albumin, sodium chloride, potassium chloride, and calcium chloride following physiological concentrations. Hydrogel contact lens was thermally polymerized using HEMA, EGDMA, and AIBN. The prepared hydrogel lens was immersed in drug for 3 hours and the eluted drug mass was measured as a function of the time. As a result, the drug was released from the lens for 12 hours in all the pH of artificial tears. At the lower pH of artificial tears (pH 5.8), the total amount of dye emitted from the lens was increased than the total amount of dye emitted at the basic tear (pH 8.4). Also, initial burst at acidic tears was increased within 1 hour. Release pattern of water-soluble drug from hydrogel lens turned out to be different depending on the pH of the artificial tears. When designing drug releasing contact lens, physiological pH of tears should be considered.

  8. Enhanced Oral Bioavailability of Efavirenz by Solid Lipid Nanoparticles: In Vitro Drug Release and Pharmacokinetics Studies

    PubMed Central

    Gaur, Praveen Kumar; Mishra, Shikha; Bajpai, Meenakshi; Mishra, Anushika

    2014-01-01

    Solid lipid nanoparticle is an efficient lipid based drug delivery system which can enhance the bioavailability of poorly water soluble drugs. Efavirenz is a highly lipophilic drug from nonnucleoside inhibitor category for treatment of HIV. Present work illustrates development of an SLN formulation for Efavirenz with increased bioavailability. At first, suitable lipid component and surfactant were chosen. SLNs were prepared and analyzed for physical parameters, stability, and pharmacokinetic profile. Efavirenz loaded SLNs were formulated using Glyceryl monostearate as main lipid and Tween 80 as surfactant. ESLN-3 has shown mean particle size of 124.5 ± 3.2 nm with a PDI value of 0.234, negative zeta potential, and 86% drug entrapment. In vitro drug release study has shown 60.6–98.22% drug release in 24 h by various SLN formulations. Optimized SLNs have shown good stability at 40°C ± 2°C and 75 ± 5% relative humidity (RH) for 180 days. ESLN-3 exhibited 5.32-fold increase in peak plasma concentration (Cmax⁡) and 10.98-fold increase in AUC in comparison to Efavirenz suspension (ES). PMID:24967360

  9. Chitosan-graft-β-cyclodextrin nanoparticles as a carrier for controlled drug release.

    PubMed

    Yuan, Zeting; Ye, Yajing; Gao, Feng; Yuan, Huihui; Lan, Minbo; Lou, Kaiyan; Wang, Wei

    2013-03-25

    Chitosan (CS) grafted with β-cyclodextrin (CD-g-CS) nanoparticles as a new carrier for poorly water-soluble drugs has been developed. The CD-g-CS polymer is readily synthesized from chitosan and mono-6-deoxy-6-(p-toluenesulfonyl)-β-cyclodextrin. Three different degrees of substitution (DS) of β-cyclodextrin (β-CD) on CD-g-CS (9.6, 14.0 and 20.0%) are designed and evaluated by controlling the mole ratio of β-CD to chitosan. Then CD-g-CS nanoparticles are prepared by an ionic gelation method, with the controlled size of 202.0-589.0 nm. Stable colloidal dispersion of the nanoparticles has been formed with the zeta potential of +23.0 to +43.0 mV. In vitro stability test indicates that CD-g-CS nanoparticles are more stable in phosphate-buffered saline compared with CS nanoparticles. Finally, the poorly water-soluble drug, ketoprofen (KTP), is used as a model drug to evaluate the efficiency of the new drug delivery carrier. It is found that the encapsulation efficiency of KTP in the nanoparticles with 20% DS of CD is as high as 1.36-fold than that of CS nanoparticles. Moreover, notably KTP is released from the nanoparticles in a controlled-release manner and is pH-responsive on DS of CD. In summary, these results suggest that the CD-g-CS nanoparticles, as a general promising drug delivery system, can be used as a potential biodegradable nano-drug delivery system for controlled release of poorly water-soluble drugs with pH-responsive capability. PMID:23422276

  10. Antiovulatory effect of ICI 33,828 (methallibure) without affecting prolactin release in normal rats.

    PubMed

    Deis, R P; Vermouth, N T

    1974-01-01

    The acute effect of 1-alpha-methylallylthiocarbamoyl-2-methylthiocarbamoylhydrazine (methall ibure) on the release of luteinizing hormone (LH) and prolactin on the day of proestrus was studied in normal rats. 21 rats received 5 mg methallibure/100 gm body weight the day before proestrus when blood samples were obtained for LH and prolactin determinations. The rats were sacrificed the examined for ova. 8 methallibure-treated rats were injected with 10 following morning (first day of estrus) and the oviducts were mcg LH/100 gm body weight on the day of estrus following blood extraction. Oviducts were examined for ova the next day. The single dose of methallibure blocked LH release in 19 out of 21 rats. The 19 rats had mean LH values of 130.2 ng/ml, highly significant (p less than .0001) when compared with 392.7 ng/ml in the controls. Prolactin release was not affected by methallibure, since the mean prolactin level for treated rats was 166.8 ng/ml and 198.7 ng/ml for the controls. The serum prolactin peak on the afternoon of proestrus was confirmed in 7 normal (31 ng/ml) and in 17 estrous rats (28.3 ng/ml). In 4 treated rats, prolactin levels determined on the day of estrus were markedly higher (61 ng/ml; p less than .0001) than in normal estrous rats. None of the rats which had subnormal LH levels showed spontaneous ovulation. However, the 10 mcg LH/100 gm body weight in previously methallibure-treated rats induced ovulation. The number of ova per rat was similar in the LH treated (9.6) and in the controls (10.6). It is concluded that methallibure prevents ovulation by centrally blocking LH release either without affecting or by stimulating prolactin release. PMID:4858373

  11. A novel composite matrix based on polymeric micelle and hydrogel as a drug carrier for the controlled release of dual drugs.

    PubMed

    Anirudhan, T S; Parvathy, J; Nair, Anoop S

    2016-01-20

    In the present work, we present a system of hydrogel/micelle composite as dual-drug release vehicle. The hydrogel is prepared from poly(ethyleneglycol) PEG and poly(vinyl alcohol) PVA. Polymeric micelles are enjoying high resurgence of interest in biomedical field as promising candidates for the stabilization and delivery of water insoluble drugs. This property was used to design and synthesize oleic acid-g-chitosan (OA-g-CS) copolymer micelles. Dual drugs, an analgesic, Tramadol (TMD) and an antibiotic, Cefixime trihydrate (CFX) were used as model drugs. The drug release behaviors of the micelle and PEG-PVA/micelle DDDS were studied as functions of pH and temperature. The release profiles were analyzed by a power law equation to reveal the release mechanism of drugs. The drug carrier vehicle was characterized and studies including swelling, effect of ionic strength, anti-oxidant, antimicrobial and in vitro drug release were carried out. The release of the two drugs was much more pronounced in the basic medium than in the acidic medium. PMID:26572454

  12. Development of an Inhaled Sustained Release Dry Powder Formulation of Salbutamol Sulphate, an Antiasthmatic Drug.

    PubMed

    Kumaresan, C; Sathishkumar, K

    2016-01-01

    The present research was aimed to develop and characterize a sustained release dry powder inhalable formulation of salbutamol sulphate. The salbutamol sulphate microparticles were prepared by solvent evaporation method using biodegradable polymer poly (D,L-lactic-co-glycolic acid) to produce salbutamol sulphate microparticle mixed with carrier respirable grade lactose for oral inhalation of dry powder. The drug content were estimated to produce 1 mg sustained release salbutamol sulphate per dose. Total four formulations K1, K2, K3 and K4 were prepared with 1:1, 1:2, 1:3, 1:4 ratio of salbutamol sulphate:poly (D,L-lactic-co-glycolic acid). The developed formulations were studied for physicochemical properties, in vitro drug relase and Anderson cascade impaction studies. The prepared formulations effectively releases drug for 12 h in diffusion bag studies. Based on dissolution performance the 1:1 ratio of salbutamol sulphate:poly (D,L-lactic-co-glycolic acid) produces in vitro release 92.57% at 12 h and having particle size of microparticles (D0.5μm) 5.02±0.6 and the pulmonary deposition of dry powder 34.5±3.21 (respiratory fraction in percentage). PMID:27168692

  13. Evaluation of photodynamic activity, photostability and in vitro drug release of zinc phthalocyanine-loaded nanocapsules.

    PubMed

    de Souza, Thiane Deprá; Ziembowicz, Francieli Isa; Müller, Debora Friedrich; Lauermann, Sâmera Cristina; Kloster, Carmen Luisa; Santos, Roberto Christ Vianna; Lopes, Leonardo Quintana Soares; Ourique, Aline Ferreira; Machado, Giovanna; Villetti, Marcos Antonio

    2016-02-15

    Nanocapsule formulations containing zinc phthalocyanine (ZnPc) were investigated as drug delivery systems for use in photodynamic therapy (PDT). ZnPc loaded chitosan, PCL, and PCL coated with chitosan nanocapsules were prepared and characterized by means of their physicochemical properties, photodynamic activity, photostability and drug release profile. All formulations presented nanometric hydrodynamic radius, around 100 nm, low polydispersity index (0.08-0.24), slightly negative zeta potential for PCL nanoparticles and positive zeta potential for suspension containing chitosan. Encapsulation efficiencies were higher than 99%. The capacity of ZnPc loaded nanocapsules to produce cytotoxic singlet oxygen ((1)O2) by irradiation with red laser was monitored using 1.3-diphenylisobenzofuran as a probe. The singlet oxygen quantum yields (ΦΔ) for ZnPc loaded chitosan nanocapsules were high and similar to that of the standard (ZnPc in DMSO), displaying excellent ability to generate (1)O2. The photosensitizer loaded nanocapsules are photostable in the timescale usually utilized in PDT and only a small photobleaching event was observed when a light dose of 610J/cm(2) was applied. The in vitro drug release studies of ZnPc from all nanocapsules demonstrated a sustained release profile controlled by diffusion, without burst effect. The nature of the polymer and the core type of the nanocapsules regulated ZnPc release. Thus, the nanocapsules developed in this work are a promising strategy to be employed in PDT. PMID:26678154

  14. Oral Sustained Release of a Hydrophilic Drug Using the Lauryl Sulfate Salt/Complex.

    PubMed

    Kasashima, Yuuki; Yoshihara, Keiichi; Yasuji, Takehiko; Sako, Kazuhiro; Uchida, Shinya; Namiki, Noriyuki

    2016-01-01

    The objective of this study was to establish the key factor of the lauryl sulfate (LS) salt/complex for sustained release of a hydrophilic drug at various physiological pH levels. Mirabegron is a hydrophilic drug that exhibits pH-dependent solubility. Sodium lauryl sulfate (SLS) bound to mirabegron in a stoichiometric manner. The formation of the LS salt/complex significantly reduced mirabegron solubility and helped achieve sustained release of mirabegron over a wide range of pH levels. In addition to SLS, other additives containing a sulfate group formed salts/complexes with mirabegron and reduced its solubility at different pH levels. Furthermore, octyl sulfate (OS), myristyl sulfate (MS), and cetyl sulfate (CS) salts/complexes, which contain alkyl chains of different lengths, showed a lower solubility than mirabegron and promoted sustained release of mirabegron. The rank order of solubility and dissolution rate were as follows: OS salt/complex>LS salt/complex>MS salt/complex>CS salt/complex, which corresponded to the rank of alkyl chain lengths. We conclude that the presence of a sulfate group and the length of the alkyl chain are key factors of the LS salt/complex for sustained release of a hydrophilic drug at various physiological pH levels. PMID:27581634

  15. Development of an Inhaled Sustained Release Dry Powder Formulation of Salbutamol Sulphate, an Antiasthmatic Drug

    PubMed Central

    Kumaresan, C.; Sathishkumar, K.

    2016-01-01

    The present research was aimed to develop and characterize a sustained release dry powder inhalable formulation of salbutamol sulphate. The salbutamol sulphate microparticles were prepared by solvent evaporation method using biodegradable polymer poly (D,L-lactic-co-glycolic acid) to produce salbutamol sulphate microparticle mixed with carrier respirable grade lactose for oral inhalation of dry powder. The drug content were estimated to produce 1 mg sustained release salbutamol sulphate per dose. Total four formulations K1, K2, K3 and K4 were prepared with 1:1, 1:2, 1:3, 1:4 ratio of salbutamol sulphate:poly (D,L-lactic-co-glycolic acid). The developed formulations were studied for physicochemical properties, in vitro drug relase and Anderson cascade impaction studies. The prepared formulations effectively releases drug for 12 h in diffusion bag studies. Based on dissolution performance the 1:1 ratio of salbutamol sulphate:poly (D,L-lactic-co-glycolic acid) produces in vitro release 92.57% at 12 h and having particle size of microparticles (D0.5μm) 5.02±0.6 and the pulmonary deposition of dry powder 34.5±3.21 (respiratory fraction in percentage). PMID:27168692

  16. Molecular recognition and controlled release in drug delivery systems based on nanostructured lipid surfactants

    NASA Astrophysics Data System (ADS)

    Angius, R.; Murgia, S.; Berti, D.; Baglioni, P.; Monduzzi, M.

    2006-08-01

    Several monoolein/water (MO/W) based liquid crystalline (LC) nanostructured mesophases have been revisited in view of the new trends of modern drug delivery formulations. The shape and amphiphilic character of the investigated lipid molecules address the preferential polar-apolar interfacial curvature and the delicate interplay of different intermolecular forces that drive self-assembly and thermodynamic stability of the nanostructures. Here some preliminary results related to the release of the antiviral drug 1-amine-adamantane hydrochloride, solubilized in the aqueous domain of bicontinuous cubic and reverse hexagonal LC phases, suggest these MO based LC phases as possible nano-depot systems for long term controlled release. Drug release was followed by conductivity measurements during a period of ten days. An effective and targeted drug delivery often requires a specific molecular recognition. With this aim, the possibility to entrap suitable molecules such as lauroylcholine (LCh, a cationic surfactant having a peptide-like polar head that can 'recognize' membrane proteins) and adenosine monophosphate disodium salt (NaAMP, an electrolyte that can 'recognize' purine receptors) has been tested. The addition of LCh to MO/W cubic gyroid (CG) LC phase causes a cubic-lamellar phase transition. The addition of NaAMP still allows the formation of the CG nanostructure. In the presence of both NaAMP and LCh again a CG LC phase forms. The bicontinuous CG LC phases have been characterized by NMR and SAXS.

  17. Modelling drug release from inert matrix systems: from moving-boundary to continuous-field descriptions.

    PubMed

    Frenning, Göran

    2011-10-10

    The purpose of this review is to provide a comprehensive overview of mathematical procedures that can be used to describe the release of drugs from inert matrix systems. The review focuses on general principles rather than particular applications. The inherent multiscale nature of the drug-release process is pointed out and multiscale modelling is exemplified for inert porous matrices. Although effects of stagnant layers and finite volumes of release media are briefly discussed, the systematic analysis is restricted to systems under sink conditions. When the initial drug loading exceeds the drug solubility in the matrix, Higuchi-type moving-boundary descriptions continue to be highly valuable for obtaining approximate analytical solutions, especially when coupled with integral balance methods. Continuous-field descriptions have decisive advantages when numerical solutions are sought. This is because the mathematical formulation reduces to a diffusion equation with a nonlinear source term, valid over the entire matrix domain. Solutions can thus be effortlessly determined for arbitrary geometries using standard numerical packages. PMID:21095224

  18. Cochlear implants and drug delivery: In vitro evaluation of dexamethasone release.

    PubMed

    Astolfi, Laura; Guaran, Valeria; Marchetti, Nicola; Olivetto, Elena; Simoni, Edi; Cavazzini, Alberto; Jolly, Claude; Martini, Alessandro

    2014-02-01

    Anti-inflammatory drugs can minimize the trauma and inflammation in the inner ear caused by cochlear implantation surgery. For this reason, much effort has recently been devoted to finding the best way to administer these anti-inflammatory drugs for a prolonged time and in a personalized dosage. One solution is constructing an electrode with a dispenser filled with anti-inflammatory drugs with a dosage adapted to suit each new cochlear implant user. The purpose of this study was to measure in vitro, by high-performance liquid chromatography-mass spectrometry assay, the amount of dexamethasone released in 78 days in a physiological solution by a filled dispenser. The drug release continued for more than 2 months in three different phases: (1) during the first 1-5 days, (2) within about 2 weeks, and (3) from about 3 weeks until the end of experiment. This release trend is in accordance with the 3 main phases of damage caused by the cochlear implantation: (1) insertion trauma within the first 2 days, (2) inflammation within 2 weeks, and finally (3) an intracochlear chronic fibrosis reaction. Future animal model studies should consider using this dispenser in order to establish its effectiveness in preventing damage caused by cochlear implantation. PMID:23997036

  19. Polyester-based microparticles of different hydrophobicity: the patterns of lipophilic drug entrapment and release.

    PubMed

    Korzhikov, Viktor; Averianov, Ilia; Litvinchuk, Evgeniia; Tennikova, Tatiana B

    2016-05-01

    The paper is devoted to the investigation of the effect of polyester hydrophobicity and ability for crystallisation on lipophilic drug loading and release from microparticles fabricated on the base of these polymers. Poly(l-lactic acid), poly(d, l-lactic acid) and poly (lactic acid-co-glycolic acid) were synthesised by ring-opening polymerisation using stannous octoate as catalyst, while poly(caprolactone) (PCL) and poly(ω-pentadecalactone) (PPDL) formation was catalysed by lipase. The particles were formed via single emulsion evaporation/diffusion method. The particles obtained were studied using SEM, XRD and DSC methods. The degradation of particles based on different polyesters, entrapment and release of a model hydrophobic drug (risperidone®) were thoroughly studied. The effect of particles hydrophobicity and crystallinity on these parameters was of most interest. The drug entrapment is greater for the hydrophobic polymers. Drug release was more rapid from crystalline particles (PLLA, PCL, PPDL), than from amorphous PDLLA and PLGA ones. PMID:26888064

  20. Preparation, drug releasing property and pharmacodynamics of soy isoflavone-loaded chitosan microspheres.

    PubMed

    Du, Zhongyan; Dou, Xiaobing; Huang, Chenyun; Gao, Jia; Hu, Linfeng; Zhu, Jiazhen; Qian, Ying; Dou, Minhua; Fan, Chunlei

    2013-01-01

    Soybean isoflavone (SIF) has anti-aging properties and many other biological functions; however, SIF is difficult to reach higher blood concentration due to its rapid metabolism. Therefore, it is of great value to design and produce a sustained-release formulation that is able to maintain a stable level of plasma concentrations. In this paper, soybean isoflavone sustained-release microsphere from chitosan and sodium alginate was prepared successfully. The important factors that determined the quality of the microspheres were the sodium alginate concentration in solution B, the ratio of soybean isoflavone to chitosan and the mixing speed. The relative yield, encapsulation efficiency and drug loading capability of SIF were much higher than the existing commercial formulations. In real gastrointestinal conditions, compared with the non-sustained release group, the release rate of SIF slowed down and the reaction time was prolonged. Animal experiments showed that sustained-release microspheres intensified the anti-aging potentials of SIF. Compared with the Non-sustained release (NSR) group mice, oral SIF/CHI microsphere treated mice were better in the Morris Water Maze Test (MWMT), the MDA level in the both plasma and brain of the sustained release (SR) group mice decreased, and SOD content was remarkably improved. PMID:24244544

  1. Degradation and drug release of phosphate glass/polycaprolactone biological composites for hard-tissue regeneration.

    PubMed

    Kim, Hae-Won; Lee, Eun-Jung; Jun, In-Kook; Kim, Hyoun-Ee; Knowles, Jonathan C

    2005-10-01

    Phosphate-based glass (P-glass) and poly(epsilon-caprolactone) (PCL) composites were fabricated in a sheet form by solvent extraction and thermal pressing methods, and the antibiotic drug Vancomycin was loaded within the composites for use as a hard-tissue regenerative. The degradation and drug-release rate of the composites in vitro were tailored by modifying the glass composition: 0.45 P(2)O(5)-x CaO-(0.55-x)Na(2)O, where x=0.2, 0.3, 0.4, and 0.5. Compared to pure PCL, all the P-glass/PCL composites degraded to a higher degree, and the composite with lower-CaO glass showed a higher material loss. This was attributed mainly to the dissolution of the glass component. The glass dissolution also increased the degradation of PCL component in the composites. The Vancomycin release from the composites was strongly dependent on the glass composition. Drug release in pure PCL was initially abrupt and flattened out over a prolonged period. However, glass/PCL composites (particularly in the glass containing higher-CaO) exhibited a reduced initial burst and a higher release rate later. Preliminary cell tests on the extracts from the glass/PCL composites showed favorable cell proliferation, but the level was dependent on the ionic concentration of the extracts. The cell proliferation on the diluted extracts from the composite with higher-CaO glass was significantly higher than that on the blank culture dish. These observations confirmed that the P-glass/PCL composites are potentially applicable for use as hard-tissue regeneration and wound-healing materials because of their controlled degradation and drug-release profile as well as enhanced cell viability. PMID:16001393

  2. Electrophysiological evidence that drug cues have greater salience than other affective stimuli in opiate addiction.

    PubMed

    Lubman, D I; Allen, N B; Peters, L A; Deakin, J F W

    2008-11-01

    Previous research has demonstrated that drug cues are able to capture attentional resources in addicted populations. However, few studies have controlled for the possibility that drug users find all motivationally significant (i.e., affective) stimuli particularly salient. We examined this issue in opiate addiction, by exploring the impact of drug-related and affective stimuli on central attentional processes. Sixteen male heroin addicts (seven on opiate pharmacotherapy and nine recently detoxified subjects) and 12 matched controls were studied. Subjects were fitted with a 32-channel electrode cap and were instructed to passively view a series of neutral, affective and opiate-related images. The P300 elicited by drug-related stimuli was significantly larger than that elicited by affective and neutral stimuli in opiate users but not controls. Baseline ratings of craving were also found to predict the degree of P300 facilitation to the drug-related stimuli in the addicted group. Further, the opiate group demonstrated an absence of the typical enhancement of ERP responses to non-drug affective stimuli. These results suggest that opiate addicts demonstrate greater cortical processing of drug cues than other types of affective stimuli. Further research is required to assess whether addiction is specifically associated with reduced sensitivity to natural rewards, aversive stimuli or affective cues in general. PMID:18208907

  3. Natural gums as sustained release carriers: development of gastroretentive drug delivery system of ziprasidone HCl

    PubMed Central

    2012-01-01

    Background Objective of this study is to show the potential use of natural gums in the development of drug delivery systems. Therefore in this work gastro retentive tablet formulations of ziprasidone HCl were developed using simplex lattice design considering concentration of okra gum, locust bean gum and HPMC K4M as independent variables. A response surface plot and multiple regression equations were used to evaluate the effect of independent variables on hardness, flag time, floating time and drug release for 1 h, 2 h, and 8 h and for 24 h. A checkpoint batch was also prepared by considering the constraints and desirability of optimized formulation to improve its in vitro performance. Significance of result was analyzed using ANOVA and p < 0.05 was considered statistically significant. Results Formulation chiefly contains locust bean gum found to be favorable for hardness and floatability but combined effect of three variables was responsible for the sustained release of drug. The in vitro drug release data of check point batch (F8) was found to be sustained well compared to the most satisfactory formulation (F7) of 7 runs. The ‘n’ value was found to be between 0.5 and 1 suggesting that release of drug follows anomalous (non-fickian) diffusion mechanism indicating both diffusion and erosion mechanism from these natural gums. Predicted results were almost similar to the observed experimental values indicating the accuracy of the design. In vivo floatability test indicated non adherence to the gastric mucosa and tablets remain buoyant for more than 24 h. Conclusions Study showed these eco-friendly natural gums can be considered as promising SR polymers. PMID:23352292

  4. Physicochemical characterization and drug-release properties of celecoxib hot-melt extruded glass solutions.

    PubMed

    Andrews, Gavin P; Abu-Diak, Osama; Kusmanto, Febe; Hornsby, Peter; Hui, Zhai; Jones, David S

    2010-11-01

    The interest in hot-melt extrusion (HME) as a drug delivery technology for the production of glass solutions is growing rapidly. HME glass solutions have a tendency to recrystallize during storage and also typically have a very dense structure, restricting the ingress of dissolution fluid and retarding drug release. In this study, we have used HME to manufacture glass solutions containing celecoxib (CX) and polyvinylpyrrolidone (PVP) and have assessed the use of supercritical carbon dioxide (scCO2) as a pore-forming agent to enhance drug release. Differential scanning calorimetry confirmed the formation of glass solutions following extrusion. All extrudates exhibited a single glass transition temperature (Tg), positioned between the Tg values of CX and PVP. The instability of glass solutions is a significant problem during storage. Stabilization may be improved through the appropriate choice of excipient to facilitate drug–polymer interactions. The Gordon–Taylor equation showed that the Tg values of all extrudates expected on ideal mixing were lower than those observed experimentally. This may be indicative of drug–polymer interactions that decrease free volume and elevate the Tg. Molecular interactions between CX and PVP were further confirmed using Fourier transform infrared and Raman spectroscopy. Storage stability of the extrudates was shown to be dependent on drug loading. Samples containing a higher CX loading were less stable, which we ascribed to decreased Tg and hence increased mobility within the drug–polymer matrix. The solubility of CX was improved through the formulation of extruded glass solutions, but release rate was relatively slow. Exposure of extrudates to scCO2 had no effect on the solid-state properties of CX but did produce a highly porous structure. The drug-release rate from extrudates after scCO2 exposure was significantly higher. PMID:21072971

  5. Thermosensitive poly(N-isopropylacrylamide-co-glycidyl methacrylate) microgels for controlled drug release.

    PubMed

    Li, Penghui; Xu, Ruizhen; Wang, Wenhao; Li, Xiaolong; Xu, Zushun; Yeung, Kelvin W K; Chu, Paul K

    2013-01-01

    A new type of thermosensitive microgels with epoxy functional groups is designed and synthesized for drug delivery. The thermosensitive poly(N-isopropylacrylamide-co-glycidyl methacrylate) (designated as P(NIPAM-co-GMA)) microgels are prepared by an emulsifier-free emulsion polymerization method and the chemical composition of the copolymer is determined by Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance ((1)H NMR). The lower critical solution temperature (LCST) of the microgels is 32°C based on the transmittance changes at 500 nm monitored by UV/visible spectrophotometry. The hydrodynamic diameter and morphology of the microgel particles are examined by dynamic light scattering (DLS) and scanning electron microscopy (SEM), respectively. The drug release properties determined using 5-FU as the drug model in vitro reveal temperature dependence and low cytotoxicity. The thermosensitive microgels have large potential as targeted anti-cancer drug carriers. PMID:23010027

  6. Mesoporous Silica Nanoparticles as Controlled Release Drug Delivery and Gene Transfection Carriers

    SciTech Connect

    Igor I. Slowing; Juan L. Viveo-Escoto; Chia-Wen Wu; Victor S. Y. Lin

    2008-04-10

    In this review, we highlight the recent research developments of a series of surface-functionalized mesoporous silica nanoparticle (MSN) materials as efficient drug delivery carriers. The synthesis of this type of MSN materials is described along with the current methods for controlling the structural properties and chemical functionalization for biotechnological and biomedical applications. We summarized the advantages of using MSN for several drug delivery applications. The recent investigations of the biocompatibility of MSN in vitro are discussed. We also describe the exciting progress on using MSN to penetrate various cell membranes in animal and plant cells. The novel concept of gatekeeping is introduced and applied to the design of a variety of stimuli-responsive nanodevices. We envision that these MSN-based systems have a great potential for a variety of drug delivery applications, such as the site-specific delivery and intracellular controlled release of drugs, genes, and other therapeutic agents.

  7. Preparation of a novel chitosan-microcapsules/starch blend film and the study of its drug-release mechanism.

    PubMed

    Huo, Weiqiang; Xie, Gancheng; Zhang, Weixin; Wang, Wei; Shan, Junyang; Liu, Hechou; Zhou, Xiaohua

    2016-06-01

    A novel drug delivery system, chitosan-microcapsules/starch blend film for antofloxacin controlled release, was prepared, and characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (X-RD), thermogravimetry and derivative thermogravimetry (TG/DTG), and scanning electron microscopy (SEM). Following incorporation of the chitosan-microcapsules in the film matrix, the synergistic interactions between these drug-carriers were significant. The thermostability and mechanical properties of the blend film were greatly improved by the incorporation of the microcapsules. The water resistance of the blend film was enhanced by increasing the content of microcapsules, indicating that the microcapsules acted as moisture barriers. After being incorporated, chitosan-microcapsules/starch blend film shows a sustained drug release. The extent of the film degradation and microcapsules swelling in the release system indicated that the drug released of the blend film was pH-sensitive. The blend film exhibited pharmacodynamic efficacy because of the efficient drug releasing. PMID:26902892

  8. Designed drug-release systems having various breathable polyurethane film-backed hydrocolloid acrylated adhesive layers for moisture healing.

    PubMed

    Chang, Ching-Hsien; Liu, Hsia-Wei; Huang, Ching-Cheng

    2014-01-01

    A series of designed drug-release systems were prepared and established for clear moisture healing. These systems were designed to have an interpenetrating polymer network (IPN) structure, which contained a breathable polyurethane film, hydrocolloidlayer, and polyacrylate adhesive layer. Breathable polyurethane film (2000 g/m(2)/24 hr) with high moisture permeability was employed as a base for new drug-release systems or wound dressings. All drug-release systems having a polyurethane film-backed hydrocolloid acrylated adhesive layer showed an increase of water uptakes with increasing time. After 114 hours, high water uptakes of drug-release systems with 20% hydrocolloid components were observed in the values of 160, 1100, and 1870% for different additional hydrocolloid components of carboxymethylcellulose, sodium alginate, and carbomer U10, respectively. New drug-release systems of polyurethane film-backed hydrocolloid/adhesive layers could be designed and established for wound care managements. PMID:25226905

  9. Interpolymer Complexation Between Polyox and Carbopol, and Its Effect on Drug Release From Matrix Tablets.

    PubMed

    Zhang, Feng; Lubach, Joseph; Na, Watson; Momin, Samad

    2016-08-01

    Interaction between Polyox N12K and Carbopol 907 was pH dependent. A hydrogen bond-induced complexation began between pH 5.0 and 6.0 in an aqueous medium, and the interpolymer complex started to precipitate when the pH fell to 4.0. This complex was amorphous with a glass transition temperature of 3.17°C. The molar ratio between ethylene oxide and acrylic acid units in the complex was 1.3:1. About 46% of the COOH groups in Carbopol 907 were H bonded to ether oxygen in Polyox. Theophylline release from tablets containing both polymers was a function of dissolution media pH, due to the pH-dependent interactions. In 0.01 N HCl, an insoluble tablet matrix formed in situ. 93% drug was released over 27 h via Fickian diffusion. In acetate buffer pH 4.0, the insoluble tablet matrix formed in situ disintegrated into tiny gel particles. Gel erosion controlled drug release at pH 4.0. These 2 polymers were unable to complex in a phosphate buffer pH 6.8. Therefore, the tablet matrix dissolved, and drug release followed the anomalous transport mechanism at pH 6.8. The release profiles in an acetate buffer pH 4.0 and phosphate buffer pH 6.8 were statistically same, and a sustained release over 12 h was achieved. PMID:27353208

  10. Chemosterilization of male sea lampreys (Petromyzon marinus) does not affect sex pheromone release

    USGS Publications Warehouse

    Siefkes, Michael J.; Bergstedt, Roger A.; Twohey, Michael B.; Li, Weiming

    2003-01-01

    Release of males sterilized by injection with bisazir is an important experimental technique in management of sea lamprey (Petromyzon marinus), an invasive, nuisance species in the Laurentian Great Lakes. Sea lampreys are semelparous and sterilization can theoretically eliminate a male's reproductive capacity and, if the ability to obtain mates is not affected, waste the sex products of females spawning with him. It has been demonstrated that spermiating males release a sex pheromone that attracts ovulating females. We demonstrated that sterilized, spermiating males also released the pheromone and attracted ovulating females. In a two-choice maze, ovulating females increased searching behavior and spent more time in the side of the maze containing chemical stimuli from sterilized, spermiating males. This attraction response was also observed in spawning stream experiments. Also, electro-olfactograms showed that female olfactory organs were equally sensitive to chemical stimuli from sterilized and nonsterilized, spermiating males. Finally, fast atom bombardment mass spectrometry showed that extracts from water conditioned with sterilized and nonsterilized, spermiating males contained the same pheromonal molecule at similar levels. We concluded that injection of bisazir did not affect the efficacy of sex pheromone in sterilized males.

  11. Endogenously produced glycosaminoglycans affecting the release of lipoprotein lipase from macrophages and the interaction with lipoproteins.

    PubMed

    Zimmermann, R; Sartipy, P; Winkler, R; Zechner, R; Hurt-Camejo, E; Kostner, G M

    2000-04-12

    Macrophages are intimately involved in the pathogenesis of atherosclerotic diseases. A key feature of this process is their uptake of various lipoproteins and subsequent transformation to foam cells. Since lipoprotein lipase (LPL) is believed to play a role in foam cell formation, we investigated if endogenously produced proteoglycans (PGs) affect the release of this enzyme from macrophages. The human leukaemic cell line THP-1 which differentiates into macrophages by treatment with phorbol ester (phorbol 12-myristate 13-acetate) served as a model. The differentiation of THP-1 macrophages promoted the release of PGs into the cell medium which caused the detachment of LPL activity from the cell surface, and prevented LPL re-uptake and inactivation. These PGs were mainly composed of chondroitin sulfate type and exerted a heparin-like effect on LPL release. LPL is known to increase the cell association of lipoproteins by the well known bridging function. Exogenous bovine LPL at a concentration of 1 microg/ml enhanced low density lipoprotein (LDL)-binding 10-fold. Endogenously produced PGs reduced LPL-mediated binding of LDL. It is proposed that the differentiation-dependent increase in the release of PGs interferes with binding of LPL and reduces lipoprotein-binding to macrophages. PMID:10760480

  12. Electrospinning of drug-loaded polymer systems: preparation, characterization and drug release

    NASA Astrophysics Data System (ADS)

    Russo, Giuseppina; Vittoria, Vittoria; Lamberti, Gaetano; Titomanlio, Giuseppe

    2010-06-01

    In this paper we formulated and characterized biomedical devices for bone tissue regeneration. These systems were realized homogenously dispersing lamellar Hydrotalcite loaded with Diclofenac Sodium in a polymeric matrix of PCL (Poly-caprolactone). These biomedical devices were obtained through the electrospinning technique that has shown many advantages with respect to others techniques, in particular very interesting micro-fiber loaded with HDik were obtained. Drug delivery results were analyzed considering a mathematical modeling to evaluate the diffusivity coefficients.

  13. The Role of Acoustic Cavitation in Ultrasound-triggered Drug Release from Echogenic Liposomes

    NASA Astrophysics Data System (ADS)

    Kopechek, Jonathan A.

    Cardiovascular disease (CVD) is the leading cause of death in the United States and globally. CVD-related mortality, including coronary heart disease, heart failure, or stroke, generally occurs due to atherosclerosis, a condition in which plaques build up within arterial walls, potentially causing blockage or rupture. Targeted therapies are needed to achieve more effective treatments. Echogenic liposomes (ELIP), which consist of a lipid membrane surrounding an aqueous core, have been developed to encapsulate a therapeutic agent and/or gas bubbles for targeted delivery and ultrasound image enhancement. Under certain conditions ultrasound can cause nonlinear bubble growth and collapse, known as "cavitation." Cavitation activity has been associated with enhanced drug delivery across cellular membranes. However, the mechanisms of ultrasound-mediated drug release from ELIP have not been previously investigated. Thus, the objective of this dissertation is to elucidate the role of acoustic cavitation in ultrasound-mediated drug release from ELIP. To determine the acoustic and physical properties of ELIP, the frequency-dependent attenuation and backscatter coefficients were measured between 3 and 30 MHz. The results were compared to a theoretical model by measuring the ELIP size distribution in order to determine properties of the lipid membrane. It was found that ELIP have a broad size distribution and can provide enhanced ultrasound image contrast across a broad range of clinically-relevant frequencies. Calcein, a hydrophilic fluorescent dye, and papaverine, a lipoph