Understanding drug release from PCL/gelatin electrospun blends.

Electrospinning is one of the efficient processes to fabricate polymeric fibrous scaffolds for several biomedical applications. Several studies have published to demonstrate drug release from electrospun scaffolds. Blends of natural and synthetic electrospun fibers provide excellent platform to combine mechanical and bioactive properties. Drug release from polymer blends is a complex process. Drug release from polymer can be dominated by one or more of following mechanisms: polymer erosion, relaxation, and degradation. In this study, electrospun polycaprolactone (PCL)-gelatin blends are investigated to understand release mechanism of Rhodamine B dye. Also, this article summarizes the effect of high-pressure carbon dioxide on drug loading and release from PCL-gelatin fibers. Results indicate that release media diffusion is a dominant mechanism for PCL-gelatin electrospun fibers. Thickness of electrospun mat becomes critical for blends with gelatin. As gelatin is highly soluble in water and has tendency of gelation, it affects diffusion of release media in and out of scaffold. This article is a key step forward in understanding release from electrospun blends.

Development of a polymeric patch impregnated with naproxen as a model of transdermal sustained release system.

This paper describes the preparation and characterization of transdermal patches impregnated with naproxen. A mixture of ethylene vinyl acetate and Eudragit E100 (80:20, w/w) is used as a polymeric matrix to obtain a thin membrane to be impregnated. Drug impregnation is carried out under pressurized CO(2) as a processing medium according to a two-step procedure. The patch is first soaked at 1000 psi and 22 °C for 2 h, and then foamed as a result of the rapid release of CO(2) pressure in order to increase the porosity of the surface. Subsequently, the naproxen solution is placed in contact with the membrane and then soaked in CO(2) at 450 psi and 37 °C for 2.5 h to enhance the mass transfer of drug into the polymer matrix. The characterization of the resulting samples by liquid chromatography, microscopy, and calorimetry provides information on naproxen content and distribution. Patches synthesized in this way are loaded with about 1% naproxen. The drug release and diffusion process through a membrane have been studied chromatographically using a Franz diffusion cell. Results have shown that a sustained delivery for more than 24 h is obtained.

Effects of orthopedic implants with a polycaprolactone polymer coating containing bone morphogenetic protein-2 on osseointegration in bones of sheep.

OBJECTIVE: To determine elution characteristics of bone morphogenetic protein (BMP)-2 from a polycaprolactone coating applied to orthopedic implants and determine effects of this coating on osseointegration. ANIMALS: 6 sheep. PROCEDURES: An in vitro study was conducted to determine BMP-2 elution from polycaprolactone-coated implants. An in vivo study was conducted to determine the effects on osseointegration when the polycaprolactone with BMP-2 coating was applied to bone screws. Osseointegration was assessed via radiography, measurement of peak removal torque and bone mineral density, and histomorphometric analysis. Physiologic response was assessed by measuring serum bone-specific alkaline phosphatase activity and uptake of bone markers. RESULTS: Mean +/- SD elution on day 1 of the in vitro study was 263 +/- 152 pg/d, which then maintained a plateau at 59.8 +/- 29.1 pg/d. Mean peak removal torque for screws coated with polycalprolactone and BMP-2 (0.91 +/- 0.65 dN x m) and screws coated with polycaprolactone alone (0.97 +/- 1.30 dN.m) did not differ significantly from that for the control screws (2.34 +/- 1.62 dN x m). Mean bone mineral densities were 0.535 +/- 0.060 g/cm(2), 0.596 +/- 0.093 g/cm(2), and 0.524 +/- 0.142 g/cm(2) for the polycaprolactone-BMP-2-coated, polycaprolactone-coated, and control screws, respectively, and did not differ significantly among groups. Histologically, bone was in closer apposition to the implant with the control screws than with either of the coated screws. CONCLUSIONS AND CLINICAL RELEVANCE: BMP-2 within the polycaprolactone coating did not stimulate osteogenesis. The polycaprolactone coating appeared to cause a barrier effect that prevented formation of new bone. A longer period or use of another carrier polymer may result in increased osseointegration.

Density functional approach for modeling CO2 pressurized polymer thin films in equilibrium.

We have used polymer density functional theory to analyze the equilibrium density profiles and interfacial properties of thin films of polymer in the presence of CO(2). Surface tension, surface excess adsorption of CO(2) on polymer surface, and width of the interface are discussed. We have shown the changes in these properties in the presence of CO(2) and with increasing film thickness and their inverse linear relationship with increasing chain length. One of our important findings is the evidence of segregation of end segments toward the interface. We have introduced a new method of representing this phenomenon by means of Delta profiles that show increase in segregation owing to the presence of CO(2) and with increasing chain length. We also make predictions for the octacosane-CO(2) binary system near the critical point of CO(2). Our results indicate qualitative trends that are comparable to the similar experimental and simulation studies.

Novel dense CO2 technique for beta-galactosidase immobilization in polystyrene microchannels.

In this study we design new fabrication techniques and demonstrate the potential of using dense CO2 for facilitating crucial steps in the fabrication of polymeric lab-on-a-chip microdevices by embedding biomolecules at temperatures well below the polymer's glass transition temperature (T(g)). These new techniques are environmentally friendly and done without the use of a clean room. Carbon dioxide at 40 degrees C and between 4.48 and 6.89 MPa was used to immobilize the biologically active molecule, beta-galactosidase (beta-gal), on the surface of polystyrene microchannels. To our knowledge, this is the first time dense CO2 has been used to directly immobilize an enzyme in a microchannel. beta-gal activity was maintained and shown via a fluorescent reaction product, after enzyme immobilization and microchannel capping by the designed fabrication steps at 40 degrees C and pressures up to 6.89 MPa.

Chemotherapeutic implants via subcritical CO2 modification.

Polymer-based biomaterials have a broad range of current applications in medicine. Many implants generate a favorable biomedical outcome solely by providing short-term mechanical stability that allows healing of the surrounding tissues. An example is polymeric reconstructive resorbable plates having initial strengths sufficient to stabilize bone segments while allowing the osteosynthesis needed to restore original function following tumor resection. Simultaneous, localized delivery of the widely employed chemotherapeutic paclitaxel following tumor removal presents a particularly desirable goal in this context. By using compressed/subcritical CO(2) at moderate pressures (as opposed to the more familiar supercritical pressures) to embed paclitaxel in clinically utilized reconstructive plating, the form of the implant can be preserved while adding an inherently localized chemotherapeutic function. In vitro tests demonstrate the efficacy of the embedded paclitaxel against adherent MCF-7 breast cancer cells within the immediate area of the polylactic acid (PLA). CO(2) can be utilized to add dual structural-chemotherapeutic function to polymeric surfaces without a change in form. The ability to 'piggyback' chemotherapeutic function into nearly any polymeric surface should find widespread utility.

Fabrication of well-defined PLGA scaffolds using novel microembossing and carbon dioxide bonding.

A novel biologically benign technique was developed to produce three-dimensional tissue engineering scaffolds with well-defined structure. Photolithography was used to design and pattern a planar scaffold skeletal structure on a photoresist (SU-8), and a variety of microembossing processes including sacrificial layer embossing and bilayer embossing were developed to transfer the skeletal pattern to the poly(DL-lactide-co-glycolide) substrate as scaffold skeletons. Subcritical carbon dioxide was then introduced to assemble these skeletons to a three-dimensional scaffold at a low temperature. Compared with conventional scaffolds, which have a broad pore size distribution and varying pore geometry, these microfabricated scaffolds have a uniform and well-defined geometry and structure. This uniformity of structural parameters allows for the studies of cell attachment, spreading, and proliferation in scaffolds in a controlled and logical manner. The cytocompatibility of these microfabricated scaffolds was tested by seeding three different cell lines with different morphologies and growth patterns into these scaffolds. All three cell lines attached well to the scaffolds and grew to high densities as observed with scanning electron microscopy. This study demonstrates a controllable method to fabricate tissue scaffolds with a well-defined 3D architecture that can be used to better elucidate the effect of structure parameters such as pore geometry and pore size on tissue growth in 3D scaffolds.

High-pressure adsorption of CO2 on NaY zeolite and model prediction of adsorption isotherms.

Supercritical carbon dioxide is an efficient solvent for adsorptive separations because it can potentially be used as both the carrier solvent for adsorption and the desorbent for regeneration. Recent results have demonstrated an anomalous peak or "hump" in the adsorption isotherm near the bulk critical point when the adsorption isotherm is plotted as a function of bulk density. This work presents new data for the adsorption and desorption of carbon dioxide in the near-critical region on a crystalline, well-structured adsorbent (NaY zeolite). The results indicate a strong affinity for CO(2) as well as a significant hump near the critical point. The lattice model previously developed by Aranovich and Donohue is applied to analyze the adsorption.