Characterization of Atrazine-Loaded Biodegradable Poly(Hydroxybutyrate-Co-Hydroxyvalerate) Microspheres

Polyhydroxybutyrate-co-hydroxyvalerate microspheres (PHBV-MS) were prepared as a delivery system for the herbicide atrazine (ATZ). Characterization of the system included investigation of in vitro release properties and genotoxicity. ATZ - PHBV-MS particle diameters showed a size distribution range of 1-13 mu m. Differential scanning calorimetry analyses indicated that ATZ was associated with the PHBV microparticles. The release profiles showed a different release behavior for the pure herbicide in solution, as compared with that containing ATZ-loaded PHBV-MS. Korsmeyer-Peppas model analyses showed that atrazine release from the microparticles occurred by a combination of diffusion through the matrix and partial diffusion through water-filled pores of the PHBV microparticles. A Lactuca sativa test result showed that the genotoxicity of ATZ-loaded PHBV-MP was decreased in relation to ATZ alone. The results demonstrate a viable biodegradable herbicide release system using atrazine for agrochemical purposes.

Physicochemical Stability of Poly(lactide-co-glycolide) Nanocapsules Containing the Local Anesthetic Bupivacaine

This paper describes the preparation of poly(DL-lactide-co-glicolide) (PLGA) nanocapsules as a drug carrier system for the local anesthetic bupivacaine. The system was characterized and its stability investigated. The results showed a size distribution with a polydispersity index of 0.12, an average diameter of 148 nm, a zeta potential of -43.5 mV and an entrapment efficiency of 75.8%. The physicochemical properties of polymeric nanocapsule suspensions (average diameter, polydispersity, zeta potential and drug association efficiency) were evaluated as a function of time to determine the formulation stability. The formulation did not display major changes in these properties over the time, and it was considered stable up to 120 days of storage at room temperature. The results reported here which refer to the initial characterization of these new formulations for the local anesthetic bupivacaine show a promising potential for future in vivo studies.

Poly(Lactide-co-Glycolide) Nanocapsules Containing Benzocaine: Influence of the Composition of the Oily Nucleus on Physico-Chemical Properties and Anesthetic Activity

The aim of this work was to investigate the influence of the oily nucleus composition on physico-chemical properties and anesthetic activity of poly (lactide-co-glycolide) nanocapsules with benzocaine.Nanocapsules containing benzocaine were prepared with three different oily nucleus composition and characterized by mean diameter, polydispersivity, zeta potential, pH and stability were investigated as a function of time. In vitro release kinetics were performed in a system with two compartments separated by a cellulose membrane. Intensity and duration of analgesia were evaluated in rats by sciatic nerve blockade.The greatest stability, slower release profile and improvement in the local anesthetic activity of BZC were obtained with the formulation using USP mineral oil as component.Results from our study provide useful perspectives on selection of the primary materials needed to produce suspensions of polymeric nanocapsules able to act as carriers of BZC, with potential future application in the treatment of pain.

Effect of temperature and a crosslinking promoter on the gamma-radiolysis of a perfluoroelastomer

Methods of promoting the radiation-induced cross linking of poly(tetrafluoro-ethylene-co-perfluoromethyl vinyl ether) (TFE/PMVE) have been investigated. Greater control of the crosslinking and chain-scission reactions was achieved by varying the radiolysis temperature. This was attributed to temperature affecting the mobilities of reactive species such as polymeric free radicals. These reactive species are precursors to radiation-induced cross links and chain-ends. Analysis of the sol/gel behaviour, tensile properties and FTIR indicated that the optimum temperature for the radiation crosslinking of TFE/PMVE, at a dose of 150 kGy, was 263 K. This temperature was 10 K below the glass transition temperature. Incorporation of 1 wt% triallyl isocyanurate (TAIC) greatly amplified the radiation crosslinking of TFE/PMVE, The dose for gelation was decreased by 70%, and the additive imparted superior mechanical properties compared to the neat irradiated TFE/PMVE. Electron spin resonance (ESR) measurements showed higher radical yields at 77 K with the 1 wt% TAIC, indicating that the crosslinking promoter was acting as a radical trap. (C) 1999 Society of Chemical Industry.

The use of F-19 NMR for new structure determination in the radiolysis of FEP

The radiation chemistry of poly(tetrafluoroethylene-co-perfluoropropylene), FEP, with a mole fraction of tetrafluoroethylene, TFE, of 0.90 has been studied under vacuum using Co-60 gamma -radiation over absorbed dose ranges up to 3.0 MGy. The radiolysis temperatures were 300, 363, 423 and 523 K. New structure formation in the copolymers was analyzed by solid-state F-19 NMR. The new structures formed in the copolymers have been identified and the G-values for the formation of new -CF3 groups was 2.2 at the lower temperatures and increased to 2.9 at 523 K. The G-value for the loss of original -CF3 groups was approximate to1.0 at all temperatures. At the lower temperatures there was a net loss of -CF-groups on irradiation, G(CF) of -1.3, -0.9 and -0.5 at 300, 363 and 423 K, respectively, but at 523 K there was a net gain with G(CF) equal to 0.8. (C) 2001 Elsevier Science B.V. All rights reserved.

Solid state F-19 NMR determination of new structure formation in FEP following radiolysis at 300 and 363 K

The radiation chemistry of FEP copolymer with a mole fraction TFE of 0.90 has been studied using Co-60 gamma -radiation at temperatures of 300 and 363 K. New structure formation in the copolymers was analysed by solid state F-19 NMR. New chain scission products were the principal new structures found. The G-value for the formation of new -CF3 groups was 2.2 and 2.1 for the radiolysis of FEP at 300 and 363 K, respectively, and the G-value for the loss of original -CF3 groups was G(-CF3) = 1.0 and 0.9 at these two temperatures, respectively. There was a nett loss of -CF- groups on irradiation, with G(-CF) of 1.3 and 0.9 at 300 and 363 K, respectively. (C) 2001 Elsevier Science Ltd. All rights reserved.

The use of NMR for determination of new structures in irradiated TFE/PMVE fluoropolymers

The radiation chemistry of two TFE/PMVE copolymers with TFE mole fractions of 0.66 and 0.81 has been studied under vacuum using Co-60 gamma -radiation over absorbed dose ranges up to 4.2 MGy. The radiolysis temperature was 313 K for both TFE/PMVE copolymers. New structure formation in the copolymers was identified by solid-state F-19 NMR and the G-values for new chain ends of 2.1 and 0.5 and for branching sites of 0.9 and 0.2 have been obtained for the TFE/PMVE with TFE mole fractions of 0.66 and 0.81, respectively. The relative yields of-O-CF3 and -CF2-CF3 chain ends were found to be proportional to the copolymer composition, but the yields of the -CF2-CF3 chain ends and -CF- branch points mere not linearly related ia the composition. rather they wets correlated with the radical yields measured at 77 K. (C) 2001 Elsevier Science Ltd. All rights reserved.

Investigation of the vapor-phase grafting of styrene onto PFA

Poly(tetrafluoroethylene-co-perfluoropropyI vinyl ether), PFA, was grafted with styrene from the vapor phase using a simultaneous radiation grafting method. The graft yields were measured as a function of the dose and dose rate and were found to be initially linearly dependent on the dose and independent of the dose rate up to dose rates of similar to3 kGy/h. However, at a dose rate of 6.2 kGy/h, the slope of the yield-grafting time plot decreased. Raman depth profiles of the grafts showed that the polystyrene concentrations were greatest near the surface of the grafted samples and decreased with depth. The maximum penetration depth of the graft depended on the radiation dose for a fixed dose rate. Fmoc-Rink loading tests showed that the grafts displayed superior loading compared to grafts prepared from bulk styrene or from styrene solutions other than methanol.

Water sorption into poly[(2-hydroxyethyl methacrylate)-co-(1-vinyl-2-pyrrolidone]at 310 K

Poly(2-hydroxyethyl methacrylate) and copolymers of 2-hydroxyethyl methacrylate (HEMA) and 1-vinyl-2-pyrrolidone (VP) in the form of cylindrical samples (approximate to8mm x 20mm) have been prepared and the sorption of water into these cylinders has been studied by the mass-uptake methods and by magnetic-resonance imaging. The equilibrium water contents for the cylinders were found to vary systematically with the copolymer composition. Diffusion of water into the cylinders was found to follow Fickian behaviour for cylinders with high HEMA contents, with the diffusion coefficients obtained from mass-uptake studies dependent on the copolymer composition, varying from 1.7 x 10(-11) m(2) s(-1) for poly(HEMA) to 2.0 x 10(-11) m(2) s(-1) for poly(HEMA-co-VP) with a composition of 1:1. However, NMR-imaging studies showed that, while the profiles of the water diffusion fronts for cylinders with high HEMA contents were Fickian, that for the 1:1 copolymer was not and indicated that the mechanism was Case III. The polymers which were rich in VP were characterized by a water-sorption process which follows Case-III behaviour. (C) 2003 Society of Chemical Industry.

NMR imaging of the diffusion of water at 310 K into poly[(2-hydroxyethyl methacrylate)-co-(tetrahydrofurfuryl methacrylate)] containing vitamin B12 or aspirin

The ingress of water into copolymers of 2-hydroxyethyl methacrylate (HEMA) and tetrahydrofurfuryl methacrylate (THFMA) loaded with either one of two model drugs, ie vitamin B-12 or aspirin, was studied at 310 K using three-dimensional nuclear magnetic resonance (3D NMR) imaging. The poly(HEMA) was loaded with 5 wt% of the drugs. From the imaging profiles it was observed that incorporation of vitamin B-12 into the polymers rich in HEMA resulted in crack formation at the interface between the rubbery region and the glassy core on sorption of water, although these cracks were 'healed' behind the diffusion front. However, for the copolymers with low HEMA contents and for those containing aspirin, no evidence for similar crack formation was found. For the copolymers loaded with 5 wt% of aspirin or vitamin B-12 the values of the water diffusion coefficients, determined by curve-fitting the relative water concentration profiles from magnetic resonance imaging (MRI) measurements, were found to be smaller than those obtained from a mass uptake study. (C) 2004 Society of Chemical Industry.

Multifunctional bioactive glass scaffolds coated with layers of poly(d,l-lactide-co-glycolide) and poly(n-isopropylacrylamide-co-acrylic acid) microgels loaded with vancomycin

A new family of multifunctional scaffolds, incorporating selected biopolymer coatings on basic Bioglass® derived foams has been developed. The polymer coatings were investigated as carrier of vancomycin which is a suitable drug to impart antibiotic function to the scaffolds. It has been proved that coating with PLGA (poly(lactic-co-glycolic acid)) with dispersed vancomycin-loaded microgels provides a rapid delivery of drug to give antibacterial effects at the wound site and a further sustained release to aid mid to long-term healing. Furthermore, the microgels also improved the bioactivity of the scaffolds by acting as nucleation sites for the formation of HA crystals in simulated body fluid. © 2013 Elsevier B.V. All rights reserved.

Poly(glycerol adipate-co-ω-pentadecalactone) spray-dried microparticles as sustained release carriers for pulmonary delivery

Purpose: The aim of this work was to optimize biodegradable polyester poly(glycerol adipate-co-ω-pentadecalactone), PGA-co-PDL, microparticles as sustained release (SR) carriers for pulmonary drug delivery. Methods: Microparticles were produced by spray drying directly from double emulsion with and without dispersibility enhancers (L-arginine and L-leucine) (0.5-1.5%w/w) using sodium fluorescein (SF) as a model hydrophilic drug. Results: Spray-dried microparticles without dispersibility enhancers exhibited aggregated powders leading to low fine particle fraction (%FPF) (28.79±3.24), fine particle dose (FPD) (14.42±1.57 μg), with a mass median aerodynamic diameter (MMAD) 2.86±0.24 μm. However, L-leucine was significantly superior in enhancing the aerosolization performance ( L-arginine:%FPF 27.61±4.49-26.57±1.85; FPD 12.40±0.99-19.54±0.16 μg and MMAD 2.18±0.35-2. 98±0.25 μm, L-leucine:%FPF 36.90±3.6-43.38±5. 6; FPD 18.66±2.90-21.58±2.46 μg and MMAD 2.55±0.03-3. 68±0.12 μm). Incorporating L-leucine (1.5%w/w) reduced the burst release (24.04±3.87%) of SF compared to unmodified formulations (41.87±2.46%), with both undergoing a square root of time (Higuchi's pattern) dependent release. Comparing the toxicity profiles of PGA-co-PDL with L-leucine (1.5%w/w) (5 mg/ml) and poly(lactide-co-glycolide), (5 mg/ml) spray-dried microparticles in human bronchial epithelial 16HBE14o-cell lines, resulted in cell viability of 85.57±5.44 and 60.66±6.75%, respectively, after 72 h treatment. Conclusion:The above data suggest that PGA-co-PDL may be a useful polymer for preparing SR microparticle carriers, together with dispersibility enhancers, for pulmonary delivery. © Springer Science+Business Media, LLC 2011.

Estudo inicial da degradação in vivo de poli(L-co-D,L ácido lático), sintetizado em laboratório, aplicado como prótese tibial em coelhos

The copolymer poly (L-co-D,L lactic acid), PLDLA, has gained prominence in the field of temporary prostheses due to the fact that their time of degradation is quite compatible with the requirement in the case of osseous fracture. In this work the in vivo degradation of devices from copolymer, as a system of plates and screws, used in fixation of the tibia of rabbits was studied. The devices were implanted in 15 adult rabbits, albinos, New Zealand race, and they were used as control devices of alloys of titanium (Ti-6Al-4V/ V grade). The use of copolymers, synthesized in the laboratory, was tested in the repair of fracture in rabbits'tibias, being assessed in the following times: 2 weeks, 2 months and 3 months. Morphological analysis of tissue surrounding the plate and screw system, for 2 weeks of implantation, showed the presence of osteoblasts, indicating a pre bone formation. After 2 months there was new bone formation in the region in contact with the polymer. This bone growth occurred simultaneously with the process of PLDLA degradation, invading the region where there was polymer and after 3 months there was an intense degradation of the copolymer and hence greater tissue invasion compared to 2 months which characterized bone formation in a region where the polymer degraded. The in vivo degradation study of the devices for PLDLA by means of histological evaluations during the period of consolidation of the fracture showed the efficiency of plate and screw system, and it was possible to check formation of bone tissue at the implantation site, without the presence of inflammatory reaction

Thermal characterization of copolymers obtained by radiation grafting of styrene onto poly(tetrafluoroethyleneperfluoropropylvinylether) substrates: thermal decomposition, melting behavior and low-temperature transitions

Differential scanning calorimetric (DSC) and thermogravimetric analysis (TGA) have been used to study the thermal decomposition, the melting behavior and low-temperature transitions of copolymers obtained by radiation-induced grafting of styrene onto poly (tetrafluoroethylene- perfluoropropylvinylether) (PFA) substrates. PFA with different contents of perfluoropropylvinylether (PPVE) as a comonomer have been investigated. A two step degradation pattern was observed from TGA thermograms of all the grafted copolymers, which was attributed to degradation of PSTY followed by the degradation of the PFA backbone at higher temperature. One broad melting peak can be identified for all copolymers, which has two components in the samples with higher PPVE content. The melting peak, crystal-crystal transition and the degree of crystallinity of the grafted copolymers increases with radiation grafting up to 50 kGy, followed by a decrease at higher doses. No such decrease was observed in the ungrafted PFA samples after irradiation. This indicated that the changes in the heats of transitions and crystallinity at low doses are due to the radiation effects on the microstructure of PFA (chain scission), whereas at higher doses the grafted PSTY is the driving force behind these changes. (C) 2001 Elsevier Science Ltd. All rights reserved.

Effect of controlled co-delivery of synergistic neurotrophic factors on early nerve regeneration in rats.

Present interventions to repair severed peripheral nerves provide slow and poor early axonal regeneration, which may cause unsatisfactory functional reinnervation. To improve early axonal regeneration in a 10 mm rat sciatic nerve gap model, we developed collagen nerve conduits loaded with the synergistically acting glial cell line-derived neurotrophic factor (GDNF) and nerve growth factor (NGF). For controlling the concomitant GDNF and NGF release, the collagen tubes were cross-linked by a dehydro-thermal treatment (110 degrees C; 20 mbar; 5 days) prior to impregnating the tubes with GDNF and NGF and by coating drug-loaded tubes with layers of poly(lactide-co-glycolide). The conduits made of cross-linked collagen released low initial amounts of GDNF and NGF (2% of both during first 3 days) and enhanced significantly the early (2 weeks) nerve regeneration in terms of axonal outgrowth and Schwann cell migration in a 10 mm rat sciatic nerve gap model, as compared to the conduits made of non-cross-linked collagen releasing higher initial amounts of GDNF and NGF (12-16% within 3 days), or those releasing GDNF alone. The enhancement of early axonal regeneration using controlled co-delivery of multiple synergistic neurotrophic factors is an important requisite for eventually establishing functional connections with the target organ.