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Drug Loading (drug + loading)
Terms modified by Drug Loading Selected AbstractsStability 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] Fabrication and Drug Delivery of Ultrathin Mesoporous Bioactive Glass Hollow FibersADVANCED FUNCTIONAL MATERIALS, Issue 9 2010Youliang Hong Abstract Ultrathin mesoporous bioactive glass hollow fibers (MBGHFs) fabricated using an electrospinning technique and combined with a phase-separation-induced agent, poly(ethylene oxide) (PEO), are described. The rapid solvent evaporation during electrospinning and the PEO-induced phase separation process demonstrated play vital roles in the formation of ultrathin bioactive glass fibers with hollow cores and mesoporous walls. Immersing the MBGHFs in simulated body fluid rapidly results in the development of a layer of enamel-like apatite mesocrystals at the fiber surfaces and apatite nanocrystals inside the hollow cores. Drug loading and release experiments indicate that the drug loading capacity and drug release behavior of the MBGHFs strongly depends on the fiber length. MBGHFs with fiber length >50,µm can become excellent carriers for drug delivery. The shortening of the fiber length reduces drug loading amounts and accelerates drug release. The MBGHFs reported here with sophisticated structure, high bioactivity, and good drug delivery capability can be a promising scaffold for hard tissue repair and wound healing when organized into 3D macroporous membranes. [source] Characterization of the physicochemical, antimicrobial, and drug release properties of thermoresponsive hydrogel copolymers designed for medical device applicationsJOURNAL OF BIOMEDICAL MATERIALS RESEARCH, Issue 2 2008David S. Jones Abstract In this study, a series of hydrogels was synthesized by free radical polymerization, namely poly(2-(hydroxyethyl)methacrylate) (pHEMA), poly(4-(hydroxybutyl)methacrylate) (pHBMA), poly(6-(hydroxyhexyl)methacrylate) (pHHMA), and copolymers composed of N -isopropylacrylamide (NIPAA), methacrylic acid (MA), NIPAA, and the above monomers. The surface, mechanical, and swelling properties (at 20 and 37°C, pH 6) of the polymers were determined using dynamic contact angle analysis, tensile analysis, and thermogravimetry, respectively. The Tg and lower critical solution temperatures (LCST) were determined using modulated DSC and oscillatory rheometry, respectively. Drug loading of the hydrogels with chlorhexidine diacetate was performed by immersion in a drug solution at 20°C ( AB-polymer Networks with Cooligoester and Poly(n -butyl acrylate) Segments as a Multifunctional Matrix for Controlled Drug ReleaseMACROMOLECULAR BIOSCIENCE, Issue 9 2010Christian Wischke Abstract Semi-crystalline AB-copolymer networks from oligo[(, -caprolactone)- co -glycolide]dimethacrylates and n -butylacrylate have recently been shown to exhibit a shape-memory functionality, which may be used for self-deploying and anchoring of implants. In this study, a family of such materials differing in their molar glycolide contents ,G was investigated to determine structure,property functional relationships of unloaded and drug loaded specimens. Drug loading and release were evaluated, as well as their degradation behavior in vitro and in vivo. Higher ,G resulted in higher loading levels by swelling and a faster release of ethacridine lactate, lower melting temperature of polymer crystallites, and a decrease in shape fixity ratio of the programmed temporary shape. For unloaded networks, the material behavior in vivo was independent of the mechanical load associated with different implantation sites and agreed well with data from in vitro degradation studies. Thus, AB networks could be used as novel matrices for biofunctional implants, e.g., for urogenital applications, which can self-anchor in vivo and provide mechanical support, release drugs, and finally degrade in the body to excretable fragments. [source] Integrated Multifunctional Nanosystems for Medical Diagnosis and TreatmentADVANCED FUNCTIONAL MATERIALS, Issue 21 2009*Article first published online: 9 OCT 200, Donglu Shi Abstract This article provides an overview on the development of integrated multifunctional nanosystems for medical diagnosis and treatment. In particular, a novel system is developed specifically for achieving simultaneous diagnosis and treatment of cancer. Critical issues are addressed on the architecture and assembly of nanocomponents based on medical requirements: targeted in vivo imaging, controlled drug release, localized hyperthermia, and toxicity. Nanotube-based carriers are summarized with surface functionalized properties. Other types of nanocarriers are also included such as super paramagnetic composite nanospheres and biodegradable hydroxylapatite nanoparticles. In addition, polymeric-based nanosystems are introduced with several novel features: they can be bio-dissolved due to environmental pH and temperature fluctuations. The nanocarriers are surface tailored with key functionalities: surface antibodies for cell targeting, anti-cancer drug loading, and magnetic nanoparticles for both hyperthermia and MRI. Future requirements, aims, and trends in the development of multifunctional nanosystems, particularly with intelligent functionalities for fundamental studies, are also provided. [source] Microencapsulation of doxycycline into poly(lactide- co -glycolide) by spray drying technique: Effect of polymer molecular weight on process parametersJOURNAL OF APPLIED POLYMER SCIENCE, Issue 6 2008Pradip Patel Abstract Poly(lactide- co -glycolide) (PLGA) polymers with three different molecular weights were prepared, and microparticles were produced by spray drying and water-in-oil-water (w/o/w) double emulsion techniques to encapsulate 86% of doxycycline (DXY), an antibiotic drug, for the use of periodontitis. Placebo and drug-loaded microspheres and pristine DXY were analyzed by Fourier transform infrared spectroscopy, which indicated no chemical interactions between DXY and PLGA. X-ray diffraction of drug-loaded microspheres confirmed the molecular level dispersion of DXY in PLGA. Scanning electron microscopy confirmed spherical nature and smooth surfaces of the microspheres. Mean particle size as measured by laser light scattering technique ranged between 10 and 25 ,m. In vitro release of DXY performed in 7.4 pH media continued up to 72 h and depended on molecular weight of PLGA and extent of DXY loading. Antimicrobial studies performed on one formulation and placebo microspheres suggested that drug concentrations during in vitro release are above the minimum inhibitory concentration (MIC) for Staphylococcus aureus growth. Overall, the release studies depended on the molecular weight of PLGA, extent of drug loading, and the method used to prepare microspheres. Statistical analyses of release data performed using the analysis of variance (ANOVA) method agreed well with experimental observations. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008 [source] Glutaraldehyde-crosslinked chitosan beads for controlled release of diclofenac sodiumJOURNAL OF APPLIED POLYMER SCIENCE, Issue 1 2007V. H. Kulkarni Abstract An inexpensive and simple method was adopted for the preparation of chitosan beads, crosslinked with glutaraldehyde (GA), for the controlled release of diclofenac sodium (DS). The beads were prepared by varying the experimental conditions such as pH, temperature, and extent of crosslinking. The absence of any chemical interaction among drug, polymer, and the crosslinking agent was confirmed by FTIR and thermal analysis. The beads were characterized by microscopy, which indicated that the particles were in the size range of 500,700 ,m and SEM studies revealed smooth surface and spherical shape of beads. The beads produced at higher temperature and extended exposure to GA exhibited lower drug content, whereas increased drug loading resulted in enhanced drug release. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 211,217, 2007 [source] Characterization of the physicochemical, antimicrobial, and drug release properties of thermoresponsive hydrogel copolymers designed for medical device applicationsJOURNAL OF BIOMEDICAL MATERIALS RESEARCH, Issue 2 2008David S. Jones Abstract In this study, a series of hydrogels was synthesized by free radical polymerization, namely poly(2-(hydroxyethyl)methacrylate) (pHEMA), poly(4-(hydroxybutyl)methacrylate) (pHBMA), poly(6-(hydroxyhexyl)methacrylate) (pHHMA), and copolymers composed of N -isopropylacrylamide (NIPAA), methacrylic acid (MA), NIPAA, and the above monomers. The surface, mechanical, and swelling properties (at 20 and 37°C, pH 6) of the polymers were determined using dynamic contact angle analysis, tensile analysis, and thermogravimetry, respectively. The Tg and lower critical solution temperatures (LCST) were determined using modulated DSC and oscillatory rheometry, respectively. Drug loading of the hydrogels with chlorhexidine diacetate was performed by immersion in a drug solution at 20°C ( Enhanced oral absorption of paclitaxel in N -deoxycholic acid- N, O -hydroxyethyl chitosan micellar system,JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 11 2010Hong Li Abstract The overall goal of this study was to develop a micellar system of paclitaxel (PTX) to enhance its oral absorption. An amphiphilic chitosan derivative, N -deoxycholic acid- N, O -hydroxyethyl chitosan (DHC), was synthesized and characterized by FTIR, 1H NMR, elemental analysis, and X-ray diffraction (XRD) techniques. The degree of substitution (DS) of hydroxyethyl group and deoxycholic acid group ranged from 89.5,114.5% and 1.11,8.17%, respectively. The critical micelle concentration (CMC) values of DHC decreased from 0.26 to 0.16,mg/mL as the DS of deoxycholic acid group increased. PTX was successfully loaded in DHC micelles with a high drug loading (31.68,±,0.14%) and entrapment efficiency (77.57,±,0.51%). The particle size of PTX-loaded DHC micelles ranged from 203.35,±,2.19 to 236.70,±,3.40,nm as the DS of deoxycholic acid group increased. After orally administration of PTX-loaded DHC micelles, the bioavailability was threefold compared with that of an orally dosed Taxol®. The single-pass intestinal perfusion studies (SPIP) showed that the intestinal absorption of micelles was via endocytosis involving a saturable process and a p-glycoprotein (P-gp)-independent way. All these indicated that the DHC micelles might be a promising tool for oral delivery of poorly water-soluble drugs. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:4543,4553, 2010 [source] Drug,polymer solubility and miscibility: Stability consideration and practical challenges in amorphous solid dispersion developmentJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 7 2010Feng Qian Abstract Drug,polymer solid dispersion has been demonstrated as a feasible approach to formulate poorly water-soluble drugs in the amorphous form, for the enhancement of dissolution rate and bioperformance. The solubility (for crystalline drug) and miscibility (for amorphous drug) in the polymer are directly related to the stabilization of amorphous drug against crystallization. Therefore, it is important for pharmaceutical scientists to rationally assess solubility and miscibility in order to select the optimal formulation (e.g., polymer type, drug loading, etc.) and recommend storage conditions, with respect to maximizing the physical stability. This commentary attempts to discuss the concepts and implications of the drug,polymer solubility and miscibility on the stabilization of solid dispersions, review recent literatures, and propose some practical strategies for the evaluation and development of such systems utilizing a working diagram. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:2941,2947, 2010 [source] Solid lipid microparticles produced by spray congealing: Influence of the atomizer on microparticle characteristics and mathematical modeling of the drug releaseJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 2 2010Nadia Passerini Abstract The first aim of the work was to evaluate the effect of atomizer design on the properties of solid lipid microparticles produced by spray congealing. Two different air atomizers have been employed: a conventional air pressure nozzle (APN) and a recently developed atomizer (wide pneumatic nozzle, WPN). Milled theophylline and Compritol® 888ATO were used to produce microparticles at drug-to-carrier ratios of 10:90, 20:80, and 30:70 using the two atomizers. The results showed that the application of different nozzles had significant impacts on the morphology, encapsulation efficiency, and drug release behavior of the microparticles. In contrast, the characteristics of the atomizer did not influence the physicochemical properties of the microparticles as differential scanning calorimetry, Hot Stage microscopy, X-ray powder diffraction, and Fourier transform infrared spectroscopy analysis demonstrated. The drug and the lipid carrier presented in their original crystalline forms in both WPN and APN systems. A second objective of this study was to develop a novel mathematical model for describing the dynamic process of drug release from the solid lipid microparticles. For WPN microparticles the model predicted the changes of the drug release behavior with particle size and drug loading, while for APN microparticles the model fitting was not as good as for the WPN systems, confirming the influence of the atomizer on the drug release behavior. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:916,931, 2010 [source] An investigation into the mechanism of dissolution rate enhancement of poorly water-soluble drugs from spray chilled gelucire 50/13 microspheresJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 1 2010Sheng Qi Abstract The production and physicochemical characterisation of spray chilled Gelucire 50/13 microspheres is described with a view to improving the dissolution of a poorly water-soluble drug, piroxicam, and understanding the fundamental mechanisms associated with the improved drug release. Thermorheological testing was developed as a fast screening method for predicting the processability of dispersions for spray chilling preparation. Spray chilled piroxicam loaded microspheres were spherical in shape with a median diameter of circa 150,µm. DSC indicated no interaction between piroxicam and lipid matrix, while HSM studies performed in polarized light mode indicated that the spheres contained distinct drug crystals. Polarising light microscopy and small-angle XRD investigations on the hydration behaviour of the lipid and the spray chilled microspheres revealed the formation of liquid crystalline phases depending on the degree of hydration. The dissolution behaviour of the piroxicam loaded microspheres showed significant improvements compared to drug alone. The particle size, drug loading and aging of the microspheres were all found to have an influence on the release behaviour. It was proposed that Gelucire 50/13 microspheres release the entrapped piroxicam via formation of a lyotropic liquid crystalline phase, which allows dissolution of the drug particles in a finely divided, high surface area and well-wetted state. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:262,274, 2010 [source] Direct drug loading into preformed porous solid dosage units by the controlled particle deposition (CPD), a new concept for improved dissolution using SCF-technologyJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 10 2008Ragna S. Wischumerski Abstract The controlled particle deposition (CPD), a supercritical fluid precipitation process, is used to load porous tablets with ibuprofen to improve drug dissolution. Porous tablets (porosity 44.3,±,5.5%), consisting of microcrystalline cellulose pellets and hydroxyethylcellulose, or sugar cubes (porosity 37.2,±,0.5%), are used as carrier material. Loading experiments are conducted at 313 K and 25 MPa, drug concentrations between 6.25 and 33.3 mg ibuprofen/mL supercritical carbon dioxide and contact times of 15.5 h or 5 min. The resulting products have drug contents of 3,5 g ibuprofen/mL void volume in the carrier. Comparison of a predicted value, calculated from pore volume and loading concentration to the actual drug concentrations yielded by the loading process demonstrates the efficiency and controllability of the process. The mean particle size d50 of deposited ibuprofen is around 25 µm, half the size of the starting material. Drug dissolution from loaded carriers is significantly increased by a rise in the dissolution coefficient from 0.07 min,1 for the starting material to 0.13 or 0.14 min,1 for the CPD products. The CPD method therefore is presented as a feasible and controllable process to load porous solid dosage forms with drug particles in order to improve dissolution. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:4416,4424, 2008 [source] Novel biopolymers as implant matrix for the delivery of ciprofloxacin: Biocompatibility, degradation, and in vitro antibiotic releaseJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 1 2007Suniket V. Fulzele Abstract The purpose of this study was to investigate the in vitro,in vivo degradation and tissue compatibility of three novel biopolymers viz. polymerized rosin (PR), glycerol ester of polymerized rosin (GPR) and pentaerythritol ester of polymerized rosin (PPR) and study their potential as implant matrix for the delivery of ciprofloxacin hydrochloride. Free films of polymers were used for in vitro degradation in PBS (pH 7.4) and in vivo in rat subcutaneous model. Sample weight loss, molecular weight decline, and morphological changes were analyzed after periodic intervals (30, 60, and 90 days) to monitor the degradation profile. Biocompatibility was evaluated by examination of the inflammatory tissue response to the implanted films on postoperative days 7, 14, 21, and 28. Furthermore, direct compression of dry blends of various polymer matrices with 20%, 30%, and 40% w/w drug loading was performed to investigate their potential for implant systems. The implants were characterized in terms of porosity and ciprofloxacin release. Biopolymer films showed slow rate of degradation, in vivo rate being faster on comparative basis. Heterogeneous bulk degradation was evident with the esterified products showing faster rates than PR. Morphologically all the films were stiff and intact with no significant difference in their appearance. The percent weight remaining in vivo was 90.70,±,6.2, 85.59,±,5.8, and 75.56,±,4.8 for PR, GPR, and PPR films respectively. Initial rapid drop in Mw was demonstrated with nearly 20.0% and 30.0% decline within 30 days followed by a steady decline to nearly 40.0% and 50.0% within 90 days following in vitro and in vivo degradation respectively. Biocompatibility demonstrated by acute and subacute tissue reactions showed minimal inflammatory reactions with prominent fibrous encapsulation and absence of necrosis demonstrating good tissue compatibility to the extent evaluated. All implants showed erosion and increase in porosity that affected the drug release. Increase in drug loading significantly altered the ciprofloxacin release in extended dissolution studies. PPR produced drug release >90% over a period of 90 days promising its utility in implant systems. The results demonstrated the utility of novel film forming biopolymers as implant matrix for controlled/sustained drug delivery with excellent biocompatibility characteristics. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96:132,144, 2007 [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] Oral peptide delivery: in-vitro evaluation of thiolated alginate/poly(acrylic acid) microparticlesJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 9 2007Alexander Greimel ABSTRACT The purpose of this study was to develop an oral thiomer-based microparticulate delivery system for insulin by ionic gelation. The microparticulate matrix consisted of either poly(acrylic acid)-cysteine (PAA-Cys) and alginate-cysteine (Alg-Cys) or the corresponding unmodified polymers (PAA, Alg). Two different viscosities of alginates were provided for the study, low and medium. Three different types of microparticles were prepared via ionic gelation with calcium (Alg, AlgPAA and AlgPAA-Cys) and their different properties evaluated in-vitro (particle size and shape, drug loading and release profile, swelling and stability). The mean particle size of all formulations ranged from 400 to 600 ,m, revealing the lowest for thiolated microparticles. SEM micrographs showed different morphological profiles for the three different types of microparticles. Encapsulation efficiency of insulin increased within the following rank order: Alg (15%) < AlgPAA (40%) < AlgPAA-Cys (65%). Alginate and AlgPAA microparticles displayed a burst release after 30 min, whereas the thiolated particles achieved a controlled release of insulin over 3 h. The swelling ratio was pH dependent: in simulated intestinal fluid microparticles exhibited a much higher water uptake compared with simulated gastric fluid. Due to the formation of intraparticulate disulfide bonds during the preparation process, thiolated particles revealed a higher stability. It was also observed that the viscosity of the two alginates used had no influence on the properties of the particles. According to these results AlgPAA-Cys microparticles obtained by ionic gelation and stabilized via disulfide bonds might be an alternative tool for the oral administration of therapeutic peptides. [source] Nanoparticle formulation enhances the delivery and activity of a vascular endothelial growth factor antisense oligonucleotide in human retinal pigment epithelial cellsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 9 2003Jithan V. Aukunuru ABSTRACT The objective of this study was to investigate the delivery and activity of a vascular endothelial growth factor (VEGF) antisense oligonucleotide in a human retinal pigment epithelial cell line (ARPE-19) using a biodegradable nanoparticulate delivery system. A 19-mer antisense phosphorothioate oligonucleotide (PS-ODN) complementary to bases 6,24 relative to the translational start site of the VEGF mRNA, a sense PS-ODN and a mismatch PS-ODN were examined for the inhibition of secretion and mRNA expression of VEGF using an enzyme-linked immunosorbent assay and reverse transcription,polymerase chain reaction, respectively. Nanoparticles of the antisense oligonucleotides were formulated using a poly(lactide-co-glycolide) (50:50) copolymer using a double emulsion solvent evaporation method. After preparing nanoparticles, drug loading, encapsulation efficiency and particle size were determined. The cells were exposed to either plain solution of oligonucleotide or nanoparticles of oligonucleotide from Day 3 through Day 6. Alternatively, the cells were incubated with PS-ODNs and lipofectin for 4h on Day 4. In all studies, VEGF secretion and mRNA expression were determined on Day 6. The particle size, drug loading and encapsulation efficiency were 252 nm, 5.5% and 16.5%, respectively. The antisense PS-ODN inhibited VEGF mRNA and protein secretion when delivered using nanoparticles or lipofectin but not in its free form. This was consistent with the ability of nanoparticles and lipofectin to elevate the cellular uptake of the oligonucleotide by 4-fold and 13-fold, respectively. Neither mismatch nor sense oligonucleotides inhibited VEGF secretion. In conclusion, biodegradable nanoparticles enhance cellular delivery of a VEGF antisense oligonucleotide and inhibit VEGF secretion and mRNA expression in a human retinal pigment epithelial cell line. [source] Morphology and temperature responsiveness,swelling relationship of poly(N -isopropylamide,chitosan) copolymers and their application to drug releaseJOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 12 2004Chia-Fen Lee Abstract Poly [N -isopropylacrylamide (NIPAAm),chitosan] crosslinked copolymer particles were synthesized by soapless emulsion copolymerization of NIPAAm and chitosan. An anionic initiator [ammonium persulfate (APS)] and a cationic initiator [2,2,-azobis(2-methylpropionamidine)dihydrochloride (AIBA)] were used to initiate the reaction of copolymerization. The chitosan,NIPAAm copolymer synthesized by using APS as the initiator showed a homogeneous morphology and exhibited the characteristic of a lower critical solution temperature (LCST). The copolymer synthesized by using AIBA as an initiator showed a core,shell morphology, and the characteristic of LCST was insignificant. The LCST of the chitosan,NIPAAm copolymer depended on the morphology of the copolymer particles. In addition, the chitosan,NIPAAm copolymer particles were processed to form copolymer disks. Then, the effect of various variables such as the chitosan/NIPAAm weight ratio, the concentration of crosslinking agent, and the pH values on the swelling ratio of chitosan,NIPAAm copolymer disks were investigated. Furthermore, caffeine was used as the model drug to study the characteristics of drug loading of the chitosan,NIPAAm copolymer disks. Variables such as the chitosan/NIPAAm weight ratio and the concentration of the crosslinking agent significantly influenced the behavior of caffeine loading. Two factors (pore size and swelling ratio) affected the behavior of caffeine release from the chitosan,NIPAAm copolymer disks. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 3029,3037, 2004 [source] Sedimentation field-flow fractionation and granulometric analysis of PLGA microspheresJOURNAL OF SEPARATION SCIENCE, JSS, Issue 15-16 2003Nathalie Faisant Abstract Sedimentation field flow fractionation operated in the steric hyperlayer mode was used to obtain fractions of defined characteristics from crude samples of poly(D,L-lactic-co-glycolic acid) microspheres which were polydisperse in size. In less than ten minutes, Sedimentation Field Flow Fractionation (SdFFF) separation yielded three analytical fractions of very different size and particle size distribution (PSD) characteristics, as determined by granulometric analyses (Coulter Counter® and image analysis of SEM). A crude sample (average size = 45 ,m, 105% size polydispersity index) was separated into fractions of 73 ,m, 56 ,m, 8 ,m average diameters which showed a PSD of 39%, 33%, 30%, respectively. Our results demonstrated that SdFFF used in conjunction with particle size analysis offers a new approach to laboratory scale production of drug vectors of a specified average size and reduced size dispersity. In the future, this could be used to select the most convenient particles for drug loading and release. [source] The disposition of free and niosomally encapsulated Rac-flurbiprofen in dairy bovinesJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2010E. O. CONFALONIERI Confalonieri, E. O., Soraci, A. L., Becaluba, M., Denzoin, L., Rodriguez, E., Riccio, B., Tapia, O. The disposition of free and niosomally encapsulated Rac-flurbiprofen in dairy bovines. J. vet. Pharmacol. Therap. 33, 9,14. Pharmacokinetic parameters were established for flurbiprofen (FBP) after intravenous (i.v.) administration (0.5 mg/kg) of niosomal and nonniosomal formulations in dairy cattle. Niosomes of FBP showed a drug loading of 92.0 ± 0.7% and the intravenous administration of the FBP niosomes to dairy cattle did not produce any immunological reaction associated to niosomal components. Niosomal FBP was slowly eliminated from plasma and mean residual time (MRT) and AUC0,t and t 1/2 values were significantly higher than those for non niosomal FBP formulations. The results presented in this study indicate that the long circulation of FBP niosomes offers a potential application for improving the pharmacokinetic parameters of short half-life drugs for clinical use. Niosomes offer new promising perspectives of drug delivery modules in bovine therapeutics. [source] Quantitative analysis of safranal in saffron extract and nanoparticle formulation by a validated high-performance thin-layer chromatographic method,PHYTOCHEMICAL ANALYSIS, Issue 3 2010Shadab Ahmad Pathan Abstract Introduction , Safranal is an effective anticonvulsant shown to act as an agonist at GABAA receptors. Nose to brain delivery via nanoparticle formulation might improve its brain delivery. A selective and sensitive analytical method is required for evaluation of safranal-based novel drug delivery systems. Objective , To develop and validate a high-performance thin-layer chromatographic (HPTLC) method for the quantitative analysis of safranal as bulk, in saffron extract and in developed safranal-loaded nanoparticle formulation. Methodology , Chromatographic separation was achieved on silica gel pre-coated TLC aluminium plates 60F-254, using n -hexane:ethyl acetate (9,:,1, v/v) as the mobile phase. Quantitative analysis was carried out by densitometry at a wavelength of 310,nm. The method was validated and applied to detect related impurities, to analyse safranal in saffron extract and to evaluate safranal-loaded nanoparticles. Results , Compact spots of safranal were observed at Rf value 0.51 ± 0.02. The method was linear (r = 0.9991) between 0.5 and 5.0,,g/spot. The intra- and inter-day precisions were 1.08,2.17 and 1. 86,3.47%, respectively. The limit of detection was 50,ng/spot and the limit of quantification was 150,ng/spot. The method proved to be accurate (recovery 97.4,102.0%) and was selective for safranal. Evaluation of safranal-loaded nanoparticle formulation demonstrated drug loading of 23.0%, encapsulation efficiency of 42.0% and sustained drug release following biphasic pattern. Conclusion , The present method is useful for the quantitative and qualitative analysis of safranal and safranal-loaded nanoparticle formulation. It provides significant advantages in terms of greater specificity and rapid analysis. Copyright © 2009 John Wiley & Sons, Ltd. [source] Preparation and properties of ionically cross-linked chitosan nanoparticlesPOLYMERS FOR ADVANCED TECHNOLOGIES, Issue 7 2009Hui Liu Abstract Chitosan nanoparticles were fabricated by a method of tripolyphosphate (TPP) cross-linking. The influence of fabrication conditions on the physical properties and drug loading and release properties was investigated by transmission electron microscopy (TEM), dynamic light scattering (DLS), and UV,vis spectroscopy. The nanoparticles could be prepared only within a zone of appropriate chitosan and TPP concentrations. The particle size and surface zeta potential can be manipulated by variation of the fabrication conditions such as chitosan/TPP ratio and concentration, solution pH and salt addition. TEM observation revealed a core,shell structure for the as-prepared nanoparticles, but a filled structure for the ciprofloxacin (CH) loaded particles. Results show that the chitosan nanoparticles were rather stable and no cytotoxicity of the chitosan nanoparticles was found in an in vitro cell culture experiment. Loading and release of CH can be modulated by the environmental factors such as solution pH and medium quality. Copyright © 2008 John Wiley & Sons, Ltd. [source] Controllable microfluidic synthesis of multiphase drug-carrying lipospheres for site-targeted therapyBIOTECHNOLOGY PROGRESS, Issue 4 2009Kanaka Hettiarachchi Abstract We report the production of micrometer-sized gas-filled lipospheres using digital (droplet-based) microfluidics technology for chemotherapeutic drug delivery. Advantages of on-chip synthesis include a monodisperse size distribution (polydispersity index (,) values of <5%) with consistent stability and uniform drug loading. Photolithography techniques are applied to fabricate novel PDMS-based microfluidic devices that feature a combined dual hydrodynamic flow-focusing region and expanding nozzle geometry with a narrow orifice. Spherical vehicles are formed through flow-focusing by the self-assembly of phospholipids to a lipid layer around the gas core, followed by a shear-induced break off at the orifice. The encapsulation of an extra oil layer between the outer lipid shell and inner bubble gaseous core allows the transport of highly hydrophobic and toxic drugs at high concentrations. Doxorubicin (Dox) entrapment is estimated at 15 mg mL,1 of particles packed in a single ordered layer. In addition, the attachment of targeting ligands to the lipid shell allows for direct vehicle binding to cancer cells. Preliminary acoustic studies of these monodisperse gas lipospheres reveal a highly uniform echo correlation of greater than 95%. The potential exists for localized drug concentration and release with ultrasound energy. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009 [source] Improving the dissolution and oral bioavailability of the poorly water-soluble drug aloe-emodin by solid dispersion with polyethylene glycol 6000DRUG DEVELOPMENT RESEARCH, Issue 5 2009Hao-gang Duan Abstract Solid dispersions (SDs) of aloe-emodin (AE) and polyethylene glycol 6000 (PEG6000) with different drug loadings were prepared, characterized by scanning electron microscopy (SEM) and differential scanning calorimetry (DSC) and evaluated for solubility and in vitro release. The oral bioavailability of AE from SD in rats was compared with the crystalline drug. Plasma concentrations of AE were determined by HPLC. After administration of crystalline AE (35,mg·kg,1) in rats, the AUC0-600 and Cmax were 393.6±77.1,mg·min·l,1 and 1.87±0.30,mg·l,1, respectively. For the PEG6000 SD of AE, AUC0-600 and Cmax were boosted to 1310.5±111.9,mg·min·l,1 and 5.86±0.47,mg·l,1, respectively. The results indicated that the oral bioavailability of AE was increased significantly. Simultaneously, the Tmax value of AE for AE crystalline was decreased from 75.6±17.3,min to 44.8±14.8,min for SD. The earlier Tmax for AE from SD indicated the higher extent of absorption for SD due to their improved dissolution rate in rat intestine. This SD approach can therefore be used to enhanced dissolution and bioavailability for poorly water-soluble drugs. Drug Dev Res, 2009. © 2009 Wiley-Liss, Inc. [source] Drug,polymer interaction and its significance on the physical stability of nifedipine amorphous dispersion in microparticles of an ammonio methacrylate copolymer and ethylcellulose binary blendJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 1 2008Jingjun Huang Abstract Using spectroscopic and thermal analysis, this study investigated drug,polymer interaction and its significance on the physical stability of drug amorphous dispersion in microparticles of an ammonio polymethacrylate copolymer (Eudragit RL®) (RL) and ethylcellulose (EC) binary blend (RL/EC,=,2:1 w/w) prepared for use in controlled release of poorly water-soluble drugs. Solid dispersion of the model drug, nifedipine in the microparticles could be described as an ideal amorphous mixture for drug loadings up to 11% w/w. The antiplasticizing effect of the polymer blend was indicated by a significant increase in the glass transition point from ,50°C for the amorphous nifedipine to ,115°C for its solid solution. Moreover, shifts in infrared vibration wavenumber of nifedipine carbonyl and amine groups suggested that the hydrogen bonds (H-bonds) originally formed among nifedipine molecules were broken and replaced by those formed between nifedipine and polymers in the microparticles. Further infrared analysis on nifedipine amorphous dispersions with a single polymer, namely RL or EC, confirmed the proposed hydrogen-bonding interactions; and their stability study results suggested that both antiplasticizing effects and hydrogen bonding of EC and RL with nifedipine might be responsible for the physical stability of the microparticles of nifedipine amorphous dispersion with a RL/EC binary blend. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:251,262, 2008 [source] Formulation and food effects on the oral absorption of a poorly water soluble, highly permeable antiretroviral agentJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 6 2002Bruce J. Aungst Abstract DPC 961 is a low-solubility, high-permeability, second-generation non-nucleoside reverse transcriptase inhibitor. The purpose of these studies was to evaluate the effects of drug substance and formulation variables on DPC 961 oral absorption, and to compare fed and fasted state oral absorption. To accomplish this, groups of four to six dogs were dosed with various formulations of DPC 961 under fasted or fed conditions, and DPC 961 pharmacokinetics were examined. Absolute oral bioavailability, based on i.v. AUC in the same dogs, was 24% after a suspension dose in fasted dogs and was 51% in fed dogs. Bioavailability with an unoptimized tablet formulation was 30% in fasted dogs and 86% in fed dogs. DPC 961 oral absorption was shown to be dependent on drug substance particle size in fasted dogs, after dosing with a tablet formulation where only the drug substance particle size was varied, but there was no difference in fed dogs. AUC and Cmax increased in proportion with increases in tablet strength from 100 to 400 mg, using tablets manufactured from a common granulation. Tablets made with 50 and 66% drug loadings showed similar relative oral bioavailabilities. Tablets prepared with two different polymorphic forms of DPC 961 were also compared, and these were found to be equivalent. These studies provided a useful component of the formulation development process, to help identify and control the variables affecting oral absorption of this potential new therapeutic agent. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:1390,1395, 2002 [source] Hydrogenated castor oil nanoparticles as carriers for the subcutaneous administration of tilmicosin: in vitro and in vivo studiesJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2009C. HAN Tilmicosin-loaded solid lipid nanoparticles (SLN) were prepared with hydrogenated castor oil (HCO) by o/w emulsion,solvent evaporation technique. The nanoparticle diameters, surface charges, drug loadings and encapsulation efficiencies of different formulations were 90,230 nm, ,6.5,,12.5 mV, 40.3,59.2% and 5.7,11.7% (w/w), respectively. In vitro release studies of the tilmicosin-loaded nanoparticles showed a sustained release and the released tilmicosin had the same antibacterial activity as that of the free drug. Pharmacokinetics study after subcutaneous administration to Balb/c mice demonstrated that a single dose of tilmicosin-loaded nanoparticles resulted in sustained serum drug levels (>0.1 ,g/mL) for 8 days, as compared with only 5 h for the same amount of tilmicosin phosphate solution. The time to maximum concentration (Tmax), half-life of absorption (T½ ab) and half-life of elimination (T½ el) of tilmicosin-loaded nanoparticles were much longer than those of tilmicosin phosphate solution. Tissue section showed that drug-loaded nanoparticles caused no inflammation at the injection site. Cytotoxicity study in cell culture and acute toxicity test in mice demonstrated that the nanoparticles had little or no toxicity. The results of this exploratory study suggest that the HCO,SLN could be a useful system for the delivery of tilmicosin by subcutaneous administration. [source]
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