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Encapsulated Drug (encapsulated + drug)
Selected AbstractsAsymmetric bolaamphiphiles from vernonia oil designed for drug deliveryEUROPEAN JOURNAL OF LIPID SCIENCE AND TECHNOLOGY, Issue 1 2010Sarina Grinberg Abstract Throughout the ages, fats, oils and their chemical derivatives have been used in a variety of medical applications, but currently they are becoming important as components in drug delivery systems. Liposomes (vesicles from phospholipids) are among the lipid-based delivery systems that have been most extensively studied. However, targeting of liposomes to specific tissues is still problematic, and attempts to overcome these limitations include developments in nano-sized monolayer vesicles made of bolaamphiphiles (compounds containing two hydrophilic headgroups at each end of an alkyl chain). This paper describes bolaamphiphile synthesis and characterization of the nano-sized vesicles formed from the bolaamphiphiles with potential application for targeted drug delivery to the brain. The starting material for the synthesis is vernonia oil (or its fatty acids or methyl esters), which is a naturally epoxidized triacylglycerol obtained from the seeds of Vernonia galamensis. The targeting mechanism is based on the hydrolysis of the amphiphile's headgroup by an enzyme abundant in the target tissue, with subsequent release of the encapsulated drug at the target site. Preliminary experiments in mice demonstrated that the marker FITC-dextran, which normally does not penetrate the blood brain barrier, is delivered into the brain when encapsulated in these vesicles. [source] Pharmacokinetics of CPX-351 (cytarabine/daunorubicin HCl) liposome injection in the mouseJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 7 2009William F. Bayne Abstract CPX-351 (cytarabine/daunorubicin liposome injection) is a liposomal formulation of a synergistic, fixed combination of the antineoplastic drugs cytarabine and daunorubicin for intravenous infusion. The two drugs are contained within the liposome in a 5:1 molar ratio, shown to be synergistic in vitro and in murine models of hematological malignancies. Mice were given a single intravenous dose of CPX-351 or conventional cytarabine and daunorubicin in saline and plasma and bone marrow were assayed for drug and lipid concentrations. A pharmacokinetic model was developed to assess the disposition of the coencapsulated drugs in mice, including the free and encapsulated fractions after measurement of the total plasma concentrations. Through the measurement of the loss of both encapsulated drug and liposomal lipid from the plasma, the routes of elimination, extravasation (uptake of encapsulated drugs into the tissues) and leak (passage of the drugs across the liposome membrane into the plasma), could be discerned. Knowing the leak rates from the liposome into the plasma and the plasma pharmacokinetics of the conventional drugs, the free drug concentrations could be predicted. The free concentrations in the bone marrow from the liposome leak in plasma could also be predicted using the bone marrow responses to the conventional drugs. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:2540,2548, 2009 [source] Solid-state solubility influences encapsulation and release of hydrophobic drugs from PLGA/PLA nanoparticlesJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 7 2004Jayanth Panyam Abstract Biodegradable nanoparticles formulated from poly(D,L -lactide- co -glycolide) (PLGA) and polylactide (PLA) polymers are being extensively investigated for various drug delivery applications. In this study, we hypothesize that the solid-state solubility of hydrophobic drugs in polymers could influence their encapsulation and release from nanoparticles. Dexamethasone and flutamide were used as model hydrophobic drugs. A simple, semiquantitative method based on drug,polymer phase separation was developed to determine the solid-state drug,polymer solubility. Nanoparticles using PLGA/PLA polymers were formulated using an emulsion,solvent evaporation technique, and were characterized for size, drug loading, and in vitro release. X-ray powder diffraction (XRD) and differential scanning calorimetry (DSC) were used to determine the physical state of the encapsulated drug. Results demonstrated that the solid-state drug,polymer solubility depends on the polymer composition, molecular weight, and end-functional groups (ester or carboxyl) in polymer chains. Higher solid-state drug,polymer solubility resulted in higher drug encapsulation in nanoparticles, but followed an inverse correlation with the percent cumulative drug released. The XRD and DSC analyses demonstrated that the drug encapsulated in nanoparticles was present in the form of a molecular dispersion (dissolved state) in the polymer, whereas in microparticles, the drug was present in both molecular dispersion and crystalline forms. In conclusion, the solid-state drug,polymer solubility affects the nanoparticle characteristics, and thus could be used as an important preformulation parameter. © 2004 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 93:1804,1814, 2004 [source] Inhibition of serum angiotensin-converting enzyme in rabbits after intravenous administration of enalaprilat-loaded intact erythrocytesJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 9 2001Mehrdad Hamidi Encapsulation of drugs in intact erythrocytes, because of the profound characteristics of these natural microspheres, has gained considerable attention in recent years. In this study, the inhibition time courses of serum angiotensin-converting enzyme (ACE) activity after intravenous administration of enalaprilat encapsulated in intact erythrocytes was evaluated and compared with free drug, in a rabbit model. Three groups of animals each received free drug, drug-loaded erythrocytes or sham-encapsulated erythrocytes. Serum ACE activity was determined in each case using the synthetic substrate hippuryl-histidyl-leucine and quantitation of the hippuric acid released by a developed and validated HPLC method. The serum ACE inhibition profiles in the three groups showed that the encapsulated drug inhibited the serum ACE more slowly, more efficiently, over a considerably longer time and in a more reproducible manner, than the free drug or sham-encapsulated erythrocytes. We conclude that the erythrocytes can serve as efficacious slow-release drug carriers for enalaprilat in circulation. [source] The Encapsulation of Bleomycin Within Chitosan Based Polymeric Vesicles Does Not Alter its BiodistributionJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 4 2000J. SLUDDEN Polymeric vesicles have recently been developed from an amphiphilic chitosan derivative,palmitoyl glycol chitosan. Their potential as a drug delivery system was evaluated using the anti-cancer compound bleomycin as a model drug. Palmitoyl glycol chitosan (GCP41) was synthesised by conjugation of palmitoyl groups to glycol chitosan. Bleomycin-containing vesicles (669 nm diameter) were prepared from a mixture of GCP41 and cholesterol by remote loading. The vesicles were imaged by freeze-fracture electron microscopy and their in-vitro stability tested. Incubation of the larger vesicles with plasma in-vitro led to a reduction of mean size by 49%, a reaction not seen with control sorbitan monostearate niosomes (215 nm in size). They also showed a higher initial drug release (1 h), but GCP41 and sorbitan monostearate vesicles retained 62% and 63% of the encapsulated drug after 24 h, respectively. The biodistribution of smaller vesicles (290 nm) prepared by extrusion through a 200-nm filter was also studied in male Balb/c mice. Encapsulation of bleomycin into polymeric vesicles did not significantly alter the pharmacokinetics of biodistribution of bleomycin in male Balb/c mice although plasma and kidney levels were slightly increased. It is concluded that the extruded GCP41 vesicles break down in plasma in-vivo and hence are unlikely to offer any therapeutic advantage over the free drug. [source] Water Vapor Permeability of Mammalian and Fish Gelatin FilmsJOURNAL OF FOOD SCIENCE, Issue 4 2006R.J. Avena-Bustillos ABSTRACT:, Water vapor permeability of cold- and warm-water fish skin gelatins films was evaluated and compared with different types of mammalian gelatins. Alaskan pollock and salmon gelatins were extracted from frozen skins, others were obtained from commercial sources. Water vapor permeability of gelatin films was determined considering differences on percent relative humidity (%RH) at the film underside. Molecular weight distribution, amino acid composition, gel strength, viscoelastic properties, pH, and clarity were also determined for each gelatin. Water vapor permeability of cold-water fish gelatin films (0.93 gmm/m2hkPa) was significantly lower than warm-water fish and mammalian gelatin films (1.31 and 1.88 gmm/m2hkPa, respectively) at 25 °C, 0/80 %RH through 0.05-mm thickness films. This was related to increased hydrophobicity due to reduced amounts of proline and hydroxyproline in cold-water fish gelatins. As expected, gel strength and gel setting temperatures were lower for cold-water fish gelatin than either warm-water fish gelatins or mammalian gelatins. This study demonstrated significant differences in physical, chemical, and rheological properties between mammalian and fish gelatins. Lower water vapor permeability of fish gelatin films can be useful particularly for applications related to reducing water loss from encapsulated drugs and refrigerated or frozen food systems. [source] Pharmacokinetics of CPX-351 (cytarabine/daunorubicin HCl) liposome injection in the mouseJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 7 2009William F. Bayne Abstract CPX-351 (cytarabine/daunorubicin liposome injection) is a liposomal formulation of a synergistic, fixed combination of the antineoplastic drugs cytarabine and daunorubicin for intravenous infusion. The two drugs are contained within the liposome in a 5:1 molar ratio, shown to be synergistic in vitro and in murine models of hematological malignancies. Mice were given a single intravenous dose of CPX-351 or conventional cytarabine and daunorubicin in saline and plasma and bone marrow were assayed for drug and lipid concentrations. A pharmacokinetic model was developed to assess the disposition of the coencapsulated drugs in mice, including the free and encapsulated fractions after measurement of the total plasma concentrations. Through the measurement of the loss of both encapsulated drug and liposomal lipid from the plasma, the routes of elimination, extravasation (uptake of encapsulated drugs into the tissues) and leak (passage of the drugs across the liposome membrane into the plasma), could be discerned. Knowing the leak rates from the liposome into the plasma and the plasma pharmacokinetics of the conventional drugs, the free drug concentrations could be predicted. The free concentrations in the bone marrow from the liposome leak in plasma could also be predicted using the bone marrow responses to the conventional drugs. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:2540,2548, 2009 [source] Drug encapsulation using supercritical fluid extraction of emulsionsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 3 2006P. Chattopadhyay Abstract The current work was aimed at evaluating a new method, supercritical fluid extraction of emulsions (SFEE), for the production of composite (e.g., polymer-drug) micro- and nanoparticles, intended for application in sustained-release drug delivery formulations. Using the proposed method, composite particles were obtained, both in a continuous or batch manner by supercritical carbon dioxide extraction of oil-in-water (o/w) emulsions. Model drugs indomethacin and ketoprofen and biodegradable polymers poly(lactic/glycolic) acid and Eudragit RS were used in order to demonstrate the effectiveness of the SFEE process for producing these particles. Stable aqueous suspensions of composite micro and nanoparticles, having sizes ranging between 0.1 and 2 µm were consistently obtained. Emulsion droplet diameter was found to be the major size control parameter. Other parameters investigated included polymer and drug concentrations in solvent and emulsion solvent fraction. The residual solvent content in the particle suspension obtained was consistently below 50 ppm. Standard dissolution tests were used to observe the sustained release phenomenon of the composite particles. The dissolution profile was characterized in terms of the intrinsic dissolution kinetic coefficients taking into account the specific surface area and solubility of the particles. It was observed that the kinetic coefficient parameter for encapsulated drugs was reduced by 2,4 orders of magnitude when compared to the unprocessed drug particles. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95:667,679, 2006 [source] | ||||||||||