Injectable microparticle-gel system for prolonged and localized lidocaine release. I. In vitro characterization

Current treatment protocol for postoperative pain is to infuse anesthetic solution around nerves or into the epidural space. This clinical practice is beset by the short duration of the anesthetic effect unless the infusion is continuous. Continuous infusion, however, requires hospitalization of the patients, thereby increasing medical costs. In addition, it also causes systemic accumulation of the drug. We reported herein a novel treatment for the postoperative pain by applying to the surgical site a biodegradable microsphere-gel system for prolonged and localized release of encapsulated anesthetic drugs. This lidocaine-containing biodegradable poly( D , L -lactic acid) (PLA) microsphere system, although being established previously by other investigators, was hindered by a burst release and a followed rapid release of the drug within several hours in vitro . In this article, we demonstrated that by a step-by-step modification of the formulation, prolonged release of lidocaine, up to several days in vitro , could be achieved. Differential scanning calorimetry revealed a lower glass transition temperature for these lidocaine-loaded microspheres comparing to that of lidocaine-free microspheres. This decreased T g explained for the tendency of the lidocaine-loaded microspheres to physically fuse at higher temperatures. In vitro studies showed that microspheres, when loaded with 35% lidocaine, yielded a threefold increase in the degradation rate. The molecular weight of PLA of the drug-loaded microspheres was reduced by 50% within a period of 1 month. Based on the results (of prolonged lidocaine release and rapid PLA microsphere degradation), this lidocaine-loaded PLA microsphere system could offer a simple solution to the treatment of postoperative pain. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 70A: 412–419, 2004Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34434/1/30086_ftp.pd

Natural-based nanocomposites for bone tissue engineering and regenerative medicine: a review

Tissue engineering and regenerative medicine has been providing exciting technologies for the development of functional substitutes aimed to repair and regenerate damaged tissues and organs. Inspired by the hierarchical nature of bone, nanostructured biomaterials are gaining a singular attention for tissue engineering, owing their ability to promote cell adhesion and proliferation, and hence new bone growth, compared with conventional microsized materials. Of particular interest are nanocomposites involving biopolymeric matrices and bioactive nanosized fi llers. Biodegradability, high mechanical strength, and osteointegration and formation of ligamentous tissue are properties required for such materials. Biopolymers are advantageous due to their similarities with extracellular matrices, specifi c degradation rates, and good biological performance. By its turn, calcium phosphates possess favorable osteoconductivity, resorbability, and biocompatibility. Herein, an overview on the available natural polymer/calcium phosphate nanocomposite materials, their design, and properties is presented. Scaffolds, hydrogels, and fi bers as biomimetic strategies for tissue engineering, and processing methodologies are described. The specifi c biological properties of the nanocomposites, as well as their interaction with cells, including the use of bioactive molecules, are highlighted. Nanocomposites in vivo studies using animal models are also reviewed and discussed.  The research leading to this work has received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement no REGPOT-CT2012-316331-POLARIS, and from QREN (ON.2 - NORTE-01-0124-FEDER-000016) cofinanced by North Portugal Regional Operational Program (ON.2 - O Novo Norte), under the National Strategic Reference Framework (NSRF), through the European Regional Development Fund (ERDF)

FORMATION OF POROUS MEMBRANES FOR DRUG DELIVERY SYSTEMS

Highly crystalline porous hollow poly (L-lactide) (PLLA) fibres suitable for the delivery of various drugs were obtained using a dry-wet spinning process. The pore structure of the fibres could be regulated by changing the spinning systems and spinning conditions. Using the spinning system PLLA-dioxane-water, fibres with a dense toplayer and a spongy sublayer were obtained. The spinning system PLLA-chloroform/toluene-methanol yielded fibres with a very open porous structure. The membrane formation of the former system probably occurs by liquid-liquid demixing followed by crystallization of the polymer rich phase. In the membrane formation process of the spinning system, PLLA-chloroform/toluene-methanol crystallization probably plays a dominant role. The membrane formation process will be related to basic principles of phase separation. The fibres are suitable for the long term zero order delivery of the contraceptive 3-ketodesogestrel and the short term zero order delivery of the cytostatic agent, cisplatin. The drugs are released by dissolution of the drug crystals in the fibre core followed by diffusion through the membrane structure. Short term release of adriamycin could be obtained through an adsorption-desorption mechanism. The pore structures of the fibres have a large influence on the release rates of the drugs investigated. When fibres with dense toplayers were used. low release rates of drugs were observed whereas fibres with well interconnected pore structures over the fibre wall showed very high release rates

Fabrication of rigid poly(lactic acid) foams via thermally induced phase separation

Rigid poly(lactic acid) (PLA) foams were prepared by thermally induced phase separation followed by solvent exchange and vacuum drying. A novel tetrahydrofuran (THF)/water solvent system was used for the induction of liquid-liquid phase separation of PLA solution at three different temperatures; 24 °C, 4 °C and −20 °C. PLA gels obtained were mechanically stabilized by replacing THF/water solvent mixture with ethanol nonsolvent. Characterization of rigid PLA foams was obtained by scanning electron microscopy, mercury intrusion porosimetry, x-ray diffractometry, infrared spectroscopy and differential scanning calorimetry analyses. Effects of fabrication parameters on the morphology and pore structure were systematically examined. The parameters investigated included; (i) polymer concentration, (ii) THF/water ratio and (iii) quench temperature. Results showed that degree of porosity and the morphology of the pores, such as the pore size and shape could be controlled by tuning the fabrication parameters. By controlling the degree of phase separation of PLA solution, foams with dual micro and nano structures were obtained

Preparation of dual-layer acetylated methyl cellulose hollow fiber membranes via co-extrusion using thermally induced phase separation and non-solvent induced phase separation methods

Dual-layer acetylated methyl cellulose (AMC) hollow fiber membranes were prepared by coupling the thermally induced phase separation (TIPS) and non-solvent induced phase separation (NIPS) methods through a co-extrusion process. The TIPS layer was optimized by investigating the effects of coagulant composition on morphology and tensile strength. The solvent in the aqueous coagulation bath caused both delayed liquid-liquid demixing and decreased polymer concentration at the membrane surface, leading to porous structure. The addition of an additive (triethylene glycol, (TEG)) to the NIPS solution resolved the adhesion instability problem of the TIPS and NIPS layers, which occurred due to the different phase separation rates. The dual-layer AMC membrane showed good mechanical strength and performance. Comparison of the fouling resistance of the AMC membranes with dual-layer polyvinylidene fluoride (PVDF) hollow fiber membranes fabricated with the same method revealed less fouling of the AMC than the PVDF hollow fiber membrane. This study demonstrated that a dual-layer AMC membrane with good mechanical strength, performance, and fouling resistance can be successfully fabricated by a one-step process of TIPS and NIPS.close0