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.

Effects of 15d-PGJ(2)-loaded poly(D,L-lactide-co-glycolide) nanocapsules on inflammation

BACKGROUND and PURPOSEThe PPAR-gamma agonist 15d-PGJ(2) is a potent anti-inflammatory agent but only at high doses. To improve the efficiency of 15d-PGJ(2), we used poly(D,L-lactide-co-glycolide) nanocapsules to encapsulate it, and function as a drug carrier system. The effects of these loaded nanocapsules (15d-PGJ(2)-NC) on inflammation induced by different stimuli were compared with those of free 15d-PGJ(2).EXPERIMENTAL APPROACHMice were pretreated (s.c.) with either 15d-PGJ(2)-NC or unloaded 15d-PGJ(2) (3, 10 or 30 mu g center dot kg-1), before induction of an inflammatory response by i.p. injection of either endotoxin (LPS), carrageenan (Cg) or mBSA (immune response).KEY RESULTSThe 15d-PGJ(2)-NC complex did not display changes in physico-chemical parameters or drug association efficiency over time, and was stable for up to 60 days of storage. Neutrophil migration induced by i.p. administration of LPS, Cg or mBSA was inhibited by 15d-PGJ(2)-NC, but not by unloaded 15d-PGJ(2). In the Cg model, 15d-PGJ(2)-NC markedly inhibited serum levels of the pro-inflammatory cytokines TNF-alpha, IL-1 beta and IL-12p70. Importantly, 15d-PGJ(2)-NC released high amounts of 15d-PGJ(2), reaching a peak between 2 and 8 h after administration. 15d-PGJ(2) was detected in mouse serum after 24 h, indicating sustained release from the carrier. When the same concentration of unloaded 15d-PGJ(2) was administered, only small amounts of 15d-PGJ(2) were found in the serum after a few hours.CONCLUSIONS and IMPLICATIONSThe present findings clearly indicate the potential of the novel anti-inflammatory 15d-PGJ(2) carrier formulation, administered systemically. The formulation enables the use of a much smaller drug dose, and is significantly more effective compared with unloaded 15d-PGJ(2).

Synthesis and characterization of biodegradable thermoplastic elastomers for medical applications: Novel copolyesters as an alternative to polylactide and poly (e-caprolactone)

421 p.

Development of semicrystalline morphology of poly(L-lactic acid) during processing of a vascular scaffold

New and promising treatments for coronary heart disease are enabled by vascular scaffolds made of poly(L-lactic acid) (PLLA), as demonstrated by Abbott Vascular’s bioresorbable vascular scaffold. PLLA is a semicrystalline polymer whose degree of crystallinity and crystalline microstructure depend on the thermal and deformation history during processing. In turn, the semicrystalline morphology determines scaffold strength and biodegradation time. However, spatially-resolved information about the resulting material structure (crystallinity and crystal orientation) is needed to interpret in vivo observations.

The first manufacturing step of the scaffold is tube expansion in a process similar to injection blow molding. Spatial uniformity of the tube microstructure is essential for the consistent production and performance of the final scaffold. For implantation into the artery, solid-state deformation below the glass transition temperature is imposed on a laser-cut subassembly to crimp it into a small diameter. Regions of localized strain during crimping are implicated in deployment behavior.

To examine the semicrystalline microstructure development of the scaffold, we employed complementary techniques of scanning electron and polarized light microscopy, wide-angle X-ray scattering, and X-ray microdiffraction. These techniques enabled us to assess the microstructure at the micro and nano length scale. The results show that the expanded tube is very uniform in the azimuthal and axial directions and that radial variations are more pronounced. The crimping step dramatically changes the microstructure of the subassembly by imposing extreme elongation and compression. Spatial information on the degree and direction of chain orientation from X-ray microdiffraction data gives insight into the mechanism by which the PLLA dissipates the stresses during crimping, without fracture. Finally, analysis of the microstructure after deployment shows that it is inherited from the crimping step and contributes to the scaffold’s successful implantation in vivo.

Electrical characterization of the rectifying contact between aluminium and electrodeposited poly(3-methylthiophene)

A detailed investigation both of the DC and of the AC electrical properties of the Schottky barrier formed between aluminium and electrodeposited poly(3-methylthiophene) is reported. The devices show rectification ratios up to 2 x 10(4) which can be increased further after post-metal annealing. The reverse characteristics of the devices follow predictions based on the image-force lowering of the Schottky barrier, from which the doping density can be estimated, As the forward voltage increases, the device current is limited by the bulk resistance of the polymer with some evidence for injection limitation at the gold counter-electrode at high bias. In the bulk-limited regime, the device current is thermally activated near room temperature with an activation energy in the range 0.2-0.3 eV. Below about 150 K the device current is almost independent of temperature. Capacitance-voltage plots obtained at frequencies well below the device relaxation frequency indicate the presence of two distinct acceptor states, A set of shallow acceptor states are active in forward bias and are believed to determine the bulk conductivity of the polymer. A set of deeper accepters are active only for very small forward voltages and for all reverse voltages, namely when band banding causes the Fermi energy to cross these states. The density of these deeper states is approximately an order of magnitude greater than that of the shallow states. Evidence is presented also for the influence of fabrication conditions on the formation of an insulating interfacial layer at the rectifying interface. The presence of such a layer leads to inversion at the polymer surface and a modification of the I-V characteristics.

Investigation of electron acceptor states in poly(3-methylthiophene)

Both the DC and AC admittance of Schottky barrier diodes formed at the interface of aluminium and poly(3-methyl thiophene) have been investigated in some detail. The capacitance-voltage plots for the devices suggest the presence of two acceptor states, one shallow and one deep. The total concentration of acceptor states, 10 24-10 26 m -3 depending on the degree of undoping, agrees well with estimates from the reverse I-V characteristics assuming image force lowering of the interfacial potential barrier.

Charge transport in poly(3-methylthiophene) schottky barrier diodes

Schottky-barrier devices were formed from electropolymerised films of poly (3-methylthiophene) (PMeT). Thermal annealing of a partially undoped film led to diodes with rectification ratios as high as 5900 at 1 V and 50,000 at 2.5 V and ideality factors slightly above 2. The temperature dependence of ac loss tangent and forward currents are identical suggesting that bulk effects dominate device behaviour event at very low forward voltages. Below 250 K forward currents are essentially independent of temperature. Preliminary TSC measurements show the presence of at least two trapping levels in the devices. © 1993.

Effect of oxygen on the electrical characteristics of field effect transistors formed from electrochemically deposited films of poly(3-methylthiophene)

Field effect devices have been formed in which the active layer is a thin film of poly(3-methylthiophene) grown electrochemically onto preformed source and drain electrodes. Although a field effect is present after electrochemical undoping, stable device characteristics with a high modulation ratio are obtained only after vacuum annealing at an elevated temperature, and only then if the devices are held in vacuo. The polymer is shown to be p type and the devices operate in accumulation only. The hole mobility in devices thermally annealed under vacuum is around 10 -3 cm 2 V -1 s -1. On exposure to ambient laboratory air, the device conductance increases by several orders of magnitude. This increase may be reversed by subjecting the device to a further high-temperature anneal under vacuum. Subsidiary experiments show that these effects are caused by the reversible doping of the polymer by gaseous oxygen.

Antiadhesive activity of poly-hydroxy butyrate biopolymer from a marine Brevibacterium casei MSI04 against shrimp pathogenic vibrios

Vibrio pathogens are causative agents of mid-culture outbreaks, and early mortality syndrome and secondary aetiology of most dreadful viral outbreaks in shrimp aquaculture. Among the pathogenic vibrios group, Vibrio alginolyticus and V. harveyi are considered as the most significant ones in the grow-out ponds of giant black tiger shrimp Penaeus monodon in India. Use of antibiotics was banned in many countries due to the emergence of antibiotic-resistant strains and accumulation of residual antibiotics in harvested shrimp. There is an urgent need to consider the use of alternative antibiotics for the control of vibriosis in shrimp aquaculture. Biofilm formation is a pathogenic and/or establishment mechanism of Vibrio spp. This study aims to develop novel safe antibiofilm and/ or antiadhesive process using PHB to contain vibrios outbreaks in shrimp aquaculture.

Minority-carrier effects in poly-phenylenevinylene as studied by electrical characterization

Electrical measurements have been performed on poly[2-methoxy, 5 ethyl (2' hexyloxy) paraphenylenevinylene] in a pn junction with silicon. These included current-voltage measurements, capacitance-voltage measurements, capacitance-transient spectroscopy, and admittance spectroscopy. The measurements show evidence for large minority-carrier injection into the polymer possibly enabled by interface states for which evidence is also found. The shallow acceptor level depth (0.12 eV) and four deep trap level activation energies (0.30 and 1.0 eV majority-carrier type; 0.48 and 1.3 eV minority-carrier type) are found. Another trap that is visible at room temperature has point-defect nature. (C) 2001 American Institute of Physics.

Electrical characterization of the rectifying contact between aluminium and electrodeposited poly(3-methylthiophene)

A detailed investigation both of the DC and of the AC electrical properties of the Schottky barrier formed between aluminium and electrodeposited poly(3-methylthiophene) is reported. The devices show rectification ratios up to 2 x 10(4) which can be increased further after post-metal annealing. The reverse characteristics of the devices follow predictions based on the image-force lowering of the Schottky barrier, from which the doping density can be estimated, As the forward voltage increases, the device current is limited by the bulk resistance of the polymer with some evidence for injection limitation at the gold counter-electrode at high bias. In the bulk-limited regime, the device current is thermally activated near room temperature with an activation energy in the range 0.2-0.3 eV. Below about 150 K the device current is almost independent of temperature. Capacitance-voltage plots obtained at frequencies well below the device relaxation frequency indicate the presence of two distinct acceptor states, A set of shallow acceptor states are active in forward bias and are believed to determine the bulk conductivity of the polymer. A set of deeper accepters are active only for very small forward voltages and for all reverse voltages, namely when band banding causes the Fermi energy to cross these states. The density of these deeper states is approximately an order of magnitude greater than that of the shallow states. Evidence is presented also for the influence of fabrication conditions on the formation of an insulating interfacial layer at the rectifying interface. The presence of such a layer leads to inversion at the polymer surface and a modification of the I-V characteristics.

Investigation of electron acceptor states in poly(3-methylthiophene)

Both the DC and AC admittance of Schottky barrier diodes formed at the interface of aluminium and poly(3-methyl thiophene) have been investigated in some detail. The capacitance-voltage plots for the devices suggest the presence of two acceptor states, one shallow and one deep. The total concentration of acceptor states, 10 24-10 26 m -3 depending on the degree of undoping, agrees well with estimates from the reverse I-V characteristics assuming image force lowering of the interfacial potential barrier.

Charge transport in poly(3-methylthiophene) schottky barrier diodes

Schottky-barrier devices were formed from electropolymerised films of poly (3-methylthiophene) (PMeT). Thermal annealing of a partially undoped film led to diodes with rectification ratios as high as 5900 at 1 V and 50,000 at 2.5 V and ideality factors slightly above 2. The temperature dependence of ac loss tangent and forward currents are identical suggesting that bulk effects dominate device behaviour event at very low forward voltages. Below 250 K forward currents are essentially independent of temperature. Preliminary TSC measurements show the presence of at least two trapping levels in the devices. © 1993.

Effect of oxygen on the electrical characteristics of field effect transistors formed from electrochemically deposited films of poly(3-methylthiophene)

Field effect devices have been formed in which the active layer is a thin film of poly(3-methylthiophene) grown electrochemically onto preformed source and drain electrodes. Although a field effect is present after electrochemical undoping, stable device characteristics with a high modulation ratio are obtained only after vacuum annealing at an elevated temperature, and only then if the devices are held in vacuo. The polymer is shown to be p type and the devices operate in accumulation only. The hole mobility in devices thermally annealed under vacuum is around 10 -3 cm 2 V -1 s -1. On exposure to ambient laboratory air, the device conductance increases by several orders of magnitude. This increase may be reversed by subjecting the device to a further high-temperature anneal under vacuum. Subsidiary experiments show that these effects are caused by the reversible doping of the polymer by gaseous oxygen.

Fiber scaffolds of poly (glycerol-dodecanedioate) and its derivative via electrospinning for neural tissue engineering

Peripheral nerves have demonstrated the ability to bridge gaps of up to 6 mm. Peripheral Nerve System injury sites beyond this range need autograft or allograft surgery. Central Nerve System cells do not allow spontaneous regeneration due to the intrinsic environmental inhibition. Although stem cell therapy seems to be a promising approach towards nerve repair, it is essential to use the distinct three-dimensional architecture of a cell scaffold with proper biomolecule embedding in order to ensure that the local environment can be controlled well enough for growth and survival. Many approaches have been developed for the fabrication of 3D scaffolds, and more recently, fiber-based scaffolds produced via the electrospinning have been garnering increasing interest, as it offers the opportunity for control over fiber composition, as well as fiber mesh porosity using a relatively simple experimental setup. All these attributes make electrospun fibers a new class of promising scaffolds for neural tissue engineering. Therefore, the purpose of this doctoral study is to investigate the use of the novel material PGD and its derivative PGDF for obtaining fiber scaffolds using the electrospinning. The performance of these scaffolds, combined with neural lineage cells derived from ESCs, was evaluated by the dissolvability test, Raman spectroscopy, cell viability assay, real time PCR, Immunocytochemistry, extracellular electrophysiology, etc. The newly designed collector makes it possible to easily obtain fibers with adequate length and integrity. The utilization of a solvent like ethanol and water for electrospinning of fibrous scaffolds provides a potentially less toxic and more biocompatible fabrication method. Cell viability testing demonstrated that the addition of gelatin leads to significant improvement of cell proliferation on the scaffolds. Both real time PCR and Immunocytochemistry analysis indicated that motor neuron differentiation was achieved through the high motor neuron gene expression using the metabolites approach. The addition of Fumaric acid into fiber scaffolds further promoted the differentiation. Based on the results, this newly fabricated electrospun fiber scaffold, combined with neural lineage cells, provides a potential alternate strategy for nerve injury repair.^