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Hydrophobic Drugs (hydrophobic + drug)
Selected AbstractsEncapsulation and Controlled Release of a Hydrophobic Drug Using a Novel Nanoparticle-Forming Hyperbranched Polyester,MACROMOLECULAR BIOSCIENCE, Issue 7 2005Jianhua Zou Abstract Summary: An amphiphilic, hyperbranched polymer suitable for use in controlled drug delivery is reported. This polymer was obtained by modification of the hyperbranched aliphatic polyester BoltornÔ H20 (H20) with succinic anhydride and then glycidyl methacrylate, and formed nanoparticles in aqueous solution. The critical association concentration was 7.4,×,10,3 g,·,L,1, as determined by fluorescence spectroscopy using pyrene as a molecular probe. A static/dynamic laser light scattering (LLS) study revealed that the average particle size was 39.4 nm with a low particle size distribution (PDI = 0.04), and that each particle was composed of about 350 amphiphilic molecules. Daidzein, a hydrophobic traditional Chinese medicine, was encapsulated during particle formation and the release properties were determined. The optimal feeding concentration of daidzein to hyperbranched polyester was 4.9,×,10,5 g,·,mL,1 to 5.0,×,10,3 g,·,mL,1 with a loading efficiency of 76.1%. In the presence of the enzyme Lipase PS, the drug loaded nanoparticles degraded in a random one-by-one manner and released the drug over a few days. This system is therefore a novel controlled drug release system based on nanoparticles formed of hyperbranched polyester. Encapsulation of daidzein by hyperbranched polyester particles. [source] Injectable Superparamagnetic Ferrogels for Controlled Release of Hydrophobic DrugsADVANCED MATERIALS, Issue 13 2009Jian Qin A ferrogel for magnetically controlled release of drugs is prepared by integration of superparamagnetic iron oxide nanoparticles and Pluronic F127 gels. The hydrophobic drug indomethacin is loaded in the ferrogel owing to the oil-in-water micellar structure. The characteristic sol,gel transition property renders the ferrogel an injectable drug carrier that will be, in principle, free from surgical implant procedure. [source] Potentiation of glycine responses by dideoxyforskolin and tamoxifen in rat spinal neuronsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2003Dominique Chesnoy-Marchais Abstract Dideoxyforskolin, a forskolin analogue unable to stimulate adenylate cyclase, and tamoxifen, an antioestrogen widely used against breast cancer, are both known to block some Cl, channels. Their effects on Cl, responses to glycine or GABA have been tested here by using whole-cell recording from cultured spinal neurons. Dideoxyforskolin (4 or 16 µm) and tamoxifen (0.2,5 µm) both potentiate responses to low glycine concentrations. They also induce blocking effects, predominant at high glycine concentrations. At 5 µm, tamoxifen increased responses to 15 µm glycine by a factor >4.5, reaching 20 in some neurons. Potentiation by extracellular dideoxyforskolin or tamoxifen persisted after intracellular application of the modulator and was not due to Zn2+ contamination. Potentiation by tamoxifen also persisted in a Ca2+ -free extracellular solution, after intracellular Ca2+ buffering and protein kinase C blockade. Thus, the critical sites of action are not intracellular. The EC50 for glycine was lowered 6.6-fold by 5 µm tamoxifen. The kinetics and voltage-dependence of the effects of tamoxifen on glycine responses support the idea that this hydrophobic drug may act from a site located within the membrane. Tamoxifen (5 µm) also increased responses to 2 µm GABA by a factor of 3.5, but barely affected peak responses to 20 µm GABA. The demonstration that tamoxifen affects some of the main inhibitory receptors should be useful for better evaluating its neurological effects. Furthermore, the results identify a new class of molecules that potentiate glycine receptor function. [source] Carrier proteins determine local pharmacokinetics and arterial distribution of paclitaxelJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 9 2001Mark A. Lovich Abstract The growing use of local drug delivery to vascular tissues has increased interest in hydrophobic compounds. The binding of these drugs to serum proteins raises their levels in solution, but hinders their distribution through tissues. Inside the arterial interstitium, viscous and steric forces and binding interactions impede drug motion. As such, this might be the ideal scenario for increasing the amount of drug delivered to, and residence time within, arterial tissues. We quantified carrier-mediated transport for paclitaxel, a model hydrophobic agent with potential use in proliferative vascular diseases, by determining, in the presence or absence of carrier proteins, the maximum concentration of drug in aqueous solution, the diffusivity in free solution, and the diffusivity in arterial tissues. Whereas solubility of paclitaxel was raised 8.1-, 21-, and 57-fold by physiologic levels of ,1 -acid glycoproteins, bovine serum albumin, and calf serum over that in protein-free solution, diffusivity of paclitaxel in free solution was reduced by 41, 49, and 74%, respectively. When paclitaxel mixed in these solutions was applied to arteries both in vitro and in vivo, drug was more abundant at the tissue interface, but protein carriers tended to retain drug in the lumen. Once within the tissue, these proteins did not affect the rate at which drug traverses the tissue because this hydrophobic drug interacted with the abundant fixed proteins and binding sites. The protein binding properties of hydrophobic compounds allow for beneficial effects on transvascular transport, deposition, and distribution, and may enable prolonged effect and rationally guide local and systemic strategies for their administration. © 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:1324,1335, 2001 [source] Stability and Drug Loading of Spontaneous Vesicles of Comb-Like PEG DerivatesMACROMOLECULAR RAPID COMMUNICATIONS, Issue 5 2007Xiaolin Li Abstract A novel comb-like derivative CPEG- g -cholesterol was prepared by the reaction of cholesteryl chloroformate with hydroxyl groups of CPEG. The TEM and SEM results showed that CPEG-cholesterol spontaneously aggregated vesicles with the membrane thickness of 4.27,±,0.48 nm. Compared with the vesicles formed by comb-like PEG (CPEG), the derivation of cholesteryl chloroformate increased the thickness of vesicle membrane and developed corrugations. The hydrophobic doxorubicin (Dox) was added into the solution of CPEG and CPEG- g -cholesterol to test their vesicle stability. The drug-loaded vesicles of CPEG- g -cholesterol still existed but those of CPEG disappeared, which indicated that stability of vesicles was enhanced by the derived cholesteryl chloroformate. The vesicles were further cross-linked by the reaction between divinyl sulfone (DVS) and the hydroxy groups in the side chains of the CPEG and CPEG- g -cholesterol. Both cross-linked vesicles of CPEG and CPEG- g -cholesterol entrapped considerable hydrophobic Dox in the vesicles membrane. The spontaneous vesicles of CPEG- g -cholesterol and the crosslinked vesicles of CPEG and CPEG- g -cholesterol might have great potential as a cargo of the hydrophobic drug. [source] Highly Porous Nano- and Microstructured Films Loaded with Bioactive Agents for Biomedical Applications: Structure,Release Profile EffectsADVANCED ENGINEERING MATERIALS, Issue 8 2009Adi Rachelson The current study focuses on the nanostructuring of our new drug-eluting porous films and its effect on the drug release profile of both hydrophilic and hydrophobic drugs. Nanostructuring was obtained using both the dispersion and the condensation methods of emulsion processing. These new highly porous nanostructured films can be used as basic elements of various drug-eluting medical devices. [source] Monodisperse Polymer Capsules: Tailoring Size, Shell Thickness, and Hydrophobic Cargo Loading via Emulsion TemplatingADVANCED FUNCTIONAL MATERIALS, Issue 10 2010Jiwei Cui Abstract The preparation of monodisperse polymer (polydopamine, PDA) capsules by a one-step interfacial polymerization of dopamine onto dimethyldiethoxysilane (DMDES) emulsion droplets and removal of the DMDES templates with ethanol is reported. The diameters of the PDA capsules can be tailored from 400,nm to 2.4,µm by varying either the DMDES emulsion condensation time or the emulsion concentration used for templating. Further, capsules with defined nanometer-scale shell thicknesses (ranging from ,10 to 30,nm) can be prepared by adjusting the emulsion concentration. This shell thickness can be increased by repeated interfacial polymerization of dopamine, with three cycles yielding capsules with a shell thickness of up to 140,nm (for a 0.6% v/v suspension). Functional substances, such as organically stabilized magnetic (Fe3O4) nanoparticles, quantum dots (CdSe/CdS), and hydrophobic drugs (thiocoraline), can be preloaded in the emulsion droplets, and following PDA coating and DMDES removal, these materials remain encapsulated in the polymer capsules. All of the unloaded and loaded PDA capsules are monodisperse and do not aggregate. This work provides new avenues for the preparation of polymer capsules with defined size and shell thickness and for the encapsulation of a range of hydrophobic substances. [source] Solubilizing efficiency and in vitro cytotoxicity of Peptoad GJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 4 2010Radhakrishna K. Maroju Abstract A novel non-ionic surfactant, Peptoad G, is evaluated for its solubilizing capacity and cytotoxicity in order to explore its possible use in aqueous formulation of hydrophobic drugs. Solubility studies were carried out using ten model hydrophobic drugs, and cytotoxicity of the surfactant was evaluated in three different cell lines using the MTT assay. It was shown that peptoad G enhances the solubility of the ten model drugs to different extents, ranging from 20- to 1100-fold, which correlated with the number of hydrogen-bonding sites on the drug molecules. The in vitro cytotoxicity studies revealed comparable cytotoxicity of peptoad G to that of cremophor EL. The results suggest peptoad G possesses potential as an alternative to conventional solubilizers in hydrophobic drug formulations. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 2196,2198, 2010 [source] Solubilization of hydrophobic drugs by methoxy poly(ethylene glycol)-block-polycaprolactone diblock copolymer micelles: Theoretical and experimental data and correlationsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 3 2008Kevin Letchford Abstract The solubilization of five model hydrophobic drugs by a series of micelle-forming, water-soluble methoxy poly(ethylene glycol)-block-polycaprolactone diblock copolymers (MePEG-b-PCL) with varying methoxy poly(ethylene glycol) (MePEG) and polycaprolactone (PCL) block lengths was investigated. Variation of the feed weight ratio of MePEG to caprolactone resulted in the synthesis of copolymers with predictable block lengths. The micelle diameter and pyrene partition coefficient (Kv) were directly related to the PCL block length whereas the critical micelle concentrations (CMC) were inversely related to the PCL block length. The aqueous solubilities of the model hydrophobic drugs, indomethacin, curcumin, plumbagin, paclitaxel, and etoposide were increased by encapsulation within the micelles. Drug solubilization was directly related to the compatibility between the solubilizate and PCL as determined by the Flory,Huggins interaction parameter (,sp). Furthermore, the concentration of solubilized drug was also directly related to the PCL block length. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:1179,1190, 2008 [source] Liposome transport of hydrophobic drugs: Gel phase lipid bilayer permeability and partitioning of the lactone form of a hydrophobic camptothecin, DB-67JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 1 2008Vijay Joguparthi Abstract The design of liposomal delivery systems for hydrophobic drug molecules having improved encapsulation efficiency and enhanced drug retention would be highly desirable. Unfortunately, the poor aqueous solubility and high membrane binding affinity of hydrophobic drugs necessitates extensive validation of experimental methods to determine both liposome loading and permeability and thus the development of a quantitative understanding of the factors governing the encapsulation and retention/release of such compounds has been slow. This report describes an efflux transport method using dynamic dialysis to study the liposomal membrane permeability of hydrophobic compounds. A mathematical model has been developed to calculate liposomal membrane permeability coefficients of hydrophobic compounds from dynamic dialysis experiments and partitioning experiments using equilibrium dialysis. Also reported is a simple method to study the release kinetics of liposome encapsulated camptothecin lactone in plasma by comparing the hydrolysis kinetics of liposome entrapped versus free drug. DB-67, a novel hydrophobic camptothecin analogue has been used as a model permeant to validate these methods. Theoretical estimates of DB-67 permeability obtained from the bulk solubility diffusion model and the "barrier-domain" solubility diffusion model are compared to the experimentally observed value. The use of dynamic dialysis in drug release studies of liposome and other nanoparticle formulations is further discussed and experimental artifacts that can arise without adequate validation are illustrated through simulations. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:400,420, 2008 [source] 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] Formulations generated from ethanol-based proliposomes for delivery via medical nebulizersJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 7 2006Abdelbary M. A. Elhissi Multilamellar and oligolamellar liposomes were produced from ethanol-based soya phosphatidylcholine proliposome formulations by addition of isotonic sodium chloride or sucrose solutions. The resultant liposomes entrapped up to 62% of available salbutamol sulfate compared with only 1.23% entrapped by conventionally prepared liposomes. Formulations were aerosolized using an air-jet nebulizer (Pari LC Plus) or a vibrating-mesh nebulizer (Aeroneb Pro small mesh, Aeroneb Pro large mesh, or Omron NE U22). All vibrating-mesh nebulizers produced aerosol droplets having larger volume median diameter (VMD) and narrower size distribution than the air-jet nebulizer. The choice of liposome dispersion medium had little effect on the performance of the Pari nebulizer. However, for the Aeroneb Pro small mesh and Omron NE U22, the use of sucrose solution tended to increase droplet VMD, and reduce aerosol mass and phospholipid outputs from the nebulizers. For the Aeroneb Pro large mesh, sucrose solution increased the VMD of nebulized droplets, increased phospholipid output and produced no effect on aerosol mass output. The Omron NE U22 nebulizer produced the highest mass output (approx. 100%) regardless of formulation, and the delivery rates were much higher for the NaCl-dispersed liposomes compared with sucrose-dispersed formulation. Nebulization produced considerable loss of entrapped drug from liposomes and this was accompanied by vesicle size reduction. Drug loss tended to be less for the vibrating-mesh nebulizers than the jet nebulizer. The large aperture size mesh (8,m) Aeroneb Pro nebulizer increased the proportion of entrapped drug delivered to the lower stage of a twin impinger. This study has demonstrated that liposomes generated from proliposome formulations can be aerosolized in small droplets using air-jet or vibrating-mesh nebulizers. In contrast to the jet nebulizer, the performance of the vibrating-mesh nebulizers was greatly dependent on formulation. The high phospholipid output produced by the nebulizers employed suggests that both air-jet and vibrating-mesh nebulization may provide the potential of delivering liposome-entrapped or solubilized hydrophobic drugs to the airways. [source] In-vitro and in-vivo evaluation of pH-responsive polymeric micelles in a photodynamic cancer therapy modelJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 2 2001J. Taillefer pH-sensitive polymeric micelles of randomly and terminally alkylated N-isopropylacrylamide copolymers were prepared and characterized. Aluminium chloride phthalocyanine (AlClPc), a second generation sensitizer for the photodynamic therapy of cancer, was incorporated in the micelles by dialysis. Their photodynamic activities were evaluated in-vitro against EMT-6 mouse mammary tumour cells and in-vivo against EMT-6 tumours implanted intradermally on each hind thigh of Balb/c mice. pH-sensitive polymeric micelles were found to exhibit greater cytotoxicity in-vitro than control Cremophor EL formulations. In the presence of chloroquine, a weak base that raises the internal pH of acidic organelles, in-vitro experiments demonstrated the importance of endosomal/lysosomal acidity for the pH-sensitive polymeric micelles to be fully effective. Biodistribution was assessed by fluorescence of tissue extracts after intravenous injection of 2 ,mol kg,1 AlClPc. The results revealed accumulation of AlClPc polymeric micelles in the liver, spleen and lungs, with a lower tumour uptake than AlClPc Cremophor EL formulations. However, polymeric micelles exhibited similar activity in-vivo to the control Cremophor EL formulations, demonstrating the higher potency of AlClPc polymeric micelles when localized in tumour tissue. It was concluded that polymeric micelles represent a good alternative to Cremophor EL preparations for the vectorization of hydrophobic drugs. [source] Micelles-Encapsulated Microcapsules for Sequential Loading of Hydrophobic and Water-Soluble DrugsMACROMOLECULAR RAPID COMMUNICATIONS, Issue 11 2010Weijun Tong Abstract Layer-by-layer (LbL) assembly was conducted on CaCO3 microparticles pre-doped with polystyrene- block -poly(acrylic acid) (PS- b -PAA) micelles, and resulted in micelles encapsulation in the microcapsules after core removal. Distribution of the micelles in the templates and capsules was characterized by transmission electron microscopy and confocal laser scanning microscopy. The micelles inside the capsules connected with each other to form a chain and network-like structure with a higher density near the capsule walls. The hydrophobic PS cores were then able to load small uncharged hydrophobic drugs while the negatively charged PAA corona could induce spontaneous deposition of water-soluble positively charged drugs such as doxorubicin. [source] Effects of Drug Hydrophobicity on Liposomal StabilityCHEMICAL BIOLOGY & DRUG DESIGN, Issue 1 2008David R. Khan A major obstacle in drug delivery is the inability to effectively deliver drugs to their intended biological target without deleterious side-effects. Delivery vehicles such as liposomes can minimize toxic side-effects by shielding the drug from reaction with unintended targets while in systemic circulation. Liposomes have the ability to accommodate both hydrophilic and hydrophobic drugs, either in the internal aqueous core or the lipid bilayer, respectively. In the present study, fluorescein and rhodamine have been used to model hydrophilic and hydrophobic drugs, respectively. We have compared the stabilities of liposomes encapsulating these fluorophores as a function of lipid content, time, and temperature. At 25 and 37 °C, liposomes containing distearoyl phosphatidylcholine as the major phospholipid component were found to be more stable over time than those containing dipalmitoyl phosphatidylcholine, regardless of the fluorophore encapsulated. Liposomes loaded with fluorescein were found to be more stable than those with rhodamine. Dipalmitoyl phosphatidylcholine liposomes that encapsulated rhodamine were the least stable. The results indicate that the physical properties of the drug cargo play a role in the stability, and hence drug delivery kinetics, of liposomal delivery systems, and desired drug release times can be achieved by adjusting/fine-tuning the lipid compositions. [source] | |||||||||||||