Biomedical subjects

Cory Berkland

Publications and source records attributed to Cory Berkland.

9 recordsLinked to original sources

PubMed2006

Cell adhesion molecules for targeted drug delivery.

Rapid advancement of the understanding of the structure and function of cell adhesion molecules (i.e., integrins, cadherins) has impacted the design and development of drugs (i.e., peptide, proteins) with the potential to treat cancer and heart and autoimmune diseases. For example, RGD peptides/peptidomimetics have been marketed as anti-thrombic agents and are being investigated for inhibiting tumor angiogenesis. Other cell adhesion peptides derived from ICAM-1 and LFA-1 sequences were found to block T-cell adhesion to vascular endothelial cells and epithelial cells; these peptides are being investigated for treating autoimmune diseases. Recent findings suggest that cell adhesion receptors such as integrins can internalize their peptide ligands into the intracellular space. Thus, many cell adhesion peptides (i.e., RGD peptide) were used to target drugs, particles, and diagnostic agents to a specific cell that has increased expression of cell adhesion receptors. This review is focused on the utilization of cell adhesion peptides and receptors in specific targeted drug delivery, diagnostics, and tissue engineering. In the future, more information on the mechanism of internalization and intracellular trafficking of cell adhesion molecules will be exploited for delivering drug molecules to a specific type of cell or for diagnosis of cancer and heart and autoimmune diseases.

Animals↗

PubMed2005

In vitro degradation of polyanhydride/polyester core-shell double-wall microspheres.

Double-wall microspheres (DWMS), comprising distinct polymer core and shell phases, are useful and interesting for controlled-release drug delivery. In particular, the presence of a surface-eroding polymer core may be expected to limit water penetration and, therefore, delay degradation of the core phase and drug release. In this study, solid microspheres and DWMS were fabricated using a surface-eroding polymer (poly[1,6-bis(p-carboxyphenoxy)hexane]; PCPH) and a bulk-eroding polymer (poly(D,L-lactide-co-glycolide); PLG). Erosion of the particles was observed by optical and electron microscopy, while polymer degradation was followed by gel permeation chromatography, during incubation in buffer at 37 degrees C. Degradation and erosion were very different depending on which polymer formed the particle shell. Nevertheless, the relatively thin (approximately 5 microm) PCPH shells could not prevent water penetration, and the PLG cores completely eroded by 6 weeks of incubation.

Chromatography, Gel↗

PubMed2005

Modeling small-molecule release from PLG microspheres: effects of polymer degradation and nonuniform drug distribution.

Modeling release of small molecules from degradable microspheres is important to the design of controlled-release drug delivery systems. Release of small molecules from poly(d,l-lactide-co-glycolide) (PLG) particles is often controlled by diffusion of the drug through the polymer and by polymer degradation. In this study, a model is developed to independently determine the contributions of each of these factors by fitting the release of piroxicam from monodisperse 50-microm microspheres made with PLG of different initial molecular weights. The dependence of the drug diffusivity on polymer molecular weight was determined from in vitro release of piroxicam from monodisperse 10-microm PLG microspheres, and the polymer degradation rate was experimentally measured using gel permeation chromatography. The model also incorporates the effect of nonuniform drug distribution within the microspheres, which is obtained from confocal fluorescence microscopy. The model results agree well with experiments despite using only one fit parameter.

Lactic Acid↗

PubMed2004

Three-month, zero-order piroxicam release from monodispersed double-walled microspheres of controlled shell thickness.

Double-walled microspheres represent an increasingly important class of drug delivery devices that provide enhanced control of drug delivery schedules. Clearly, the overall particle size and shell thickness are important parameters in modulating the drug release rates. Precision particle fabrication technology has been used to fabricate double-walled microspheres of predefined uniform diameters of 40-60 microm exhibiting a poly(D,L-lactide-co-glycolide) (PLG) core and poly(L-lactide) (PL) shell of controllable thickness from approximately 2 to 10 microm. The release of a model small-molecule drug, piroxicam, from uniform microspheres of pure PLG and PL is compared to the release from double-walled microspheres exhibiting different PL shell thicknesses. The presence of the PL shell enveloping a PLG core essentially eliminated the initial "burst" of piroxicam that was observed when the drug was released from pure PLG microspheres. In addition, increasing the PL shell thickness shifted the release profile from a biphasic shape for pure PLG microspheres to zero-order piroxicam release over 3 months for the thickest (approximately 10 microm) PL shell.

Drug Delivery Systems↗

PubMed2004

Uniform double-walled polymer microspheres of controllable shell thickness.

A method for fabricating uniform double-walled microspheres with controllable size and shell thickness has been developed. The method, based on previous work to fabricate uniform microspheres, employs multiple concentric nozzles to produce a smooth coaxial jet comprising an annular shell and core material, which is acoustically excited to break up into uniform core-shell droplets. The orientation of the jets, material flow rates, and rate of solvent extraction are controlled to create uniform and well-centered "double-walled" microspheres exhibiting a controllable shell thickness. Double-walled microspheres were fabricated with different arrangements of bulk-eroding poly(D,L-lactide-co-glycolide) (PLG) and surface-eroding poly[(1,6-bis-carboxyphenoxy) hexane] (PCPH). Variation of the fabrication parameters allowed complete encapsulation by the shell phase, including the efficient formation of a PCPH shell encapsulating a PLG core. Utilizing this technology, double-walled microsphere shell thickness can be varied from <2 microm to tens of microns while maintaining complete and well-centered core encapsulation for double-walled microspheres near 50 microm in overall diameter.

Microspheres↗

PubMed2004

Microsphere size, precipitation kinetics and drug distribution control drug release from biodegradable polyanhydride microspheres.

A thorough understanding of the factors affecting drug release mechanisms from surface-erodible polymer devices is critical to the design of optimal delivery systems. Poly(sebacic anhydride) (PSA) microspheres were loaded with three model drug compounds (rhodamine B, p-nitroaniline and piroxicam) with a range of polarities (water solubilities). The drug release profiles from monodisperse particles of three different sizes were compared to release from polydisperse microspheres. Each of the model drugs exhibited different release mechanisms. Drug distribution within the polymer was investigated by laser scanning confocal microscopy and scanning electron microscopy. Rhodamine, the most hydrophilic compound investigated, was localized strongly toward the microsphere surface, while the much more hydrophobic compound, piroxicam, distributed more evenly. Furthermore, all three compounds were most uniformly distributed in the smallest microspheres, most likely due to the competing effects of drug diffusion out of the nascent polymer droplets and the precipitation of polymer upon solvent extraction, which effectively "traps" the drug in the polymer matrix. The differing drug distributions were manifested in the drug release profiles. Rhodamine was released very quickly independent of microsphere size. Thus, extended release profiles may not be obtainable if the drug strongly redistributes in the microspheres. The release of p-nitroaniline was more prolonged, but still showed little dependence on microsphere size. Hence, when water-soluble drugs are encapsulated with hydrophobic polymers, it may be difficult to tailor release profiles by controlling microsphere size. The piroxicam-loaded microspheres exhibit the most interesting release profiles, showing that release duration can be increased by decreasing microsphere size, resulting in a more uniform drug distribution.

Anhydrides↗

PubMed2004

Controlling surface nano-structure using flow-limited field-injection electrostatic spraying (FFESS) of poly(D,L-lactide-co-glycolide).

Improved control of surface micro- and nano-structure may lead to enhanced performance of degradable biomedical devices such as surgical dressings, vascular grafts, tissue engineering scaffolds, sutures, and structures for guided tissue regeneration. An electrohydrodynamic method called flow-limited field-injection electrostatic spraying (FFESS) has been developed as an improved technique for the controlled deposition of polymeric material. Injecting charge using a nano-sharpened tungsten needle in a process called field ionization can efficiently induce an ionic state in a solution of poly(D,L-lactide-co-glycolide) increasing its capacity to carry charge. As a result, sprays have been produced that are finer and more precisely controlled than sprays produced by conventional electrospraying techniques, which employ hypodermic needles as the spray nozzle. Here, the effect of FFESS variables including applied voltage, polymer solution flow rate, and solvent properties (surface tension, viscosity, vapor pressure) on spray performance have been qualitatively evaluated. Under certain conditions, increasing the applied voltage produced an increasingly rough surface morphology. Similarly, by reducing solvent surface tension and increasing solvent vapor pressure, more distinct surface structures could be formed including uniform nanoparticles. Working ranges of the important parameters for the production of specific structure types such as smooth or porous surfaces, non-woven or melded fibers, and distinct or melded nanoparticles have been defined. FFESS technology provides a simple yet powerful technique for fabricating biomedical devices with a precisely defined nano-structure potentially capable of utilizing a broad range of biocompatible polymeric materials.

Biocompatible Materials↗

PubMed2003

PLG microsphere size controls drug release rate through several competing factors.

PURPOSE: Although the rate of drug release from poly(D,L-lactide-co-glycolide) (PLG) microspheres is often modulated by changing fabrication conditions or materials, the specific factors directly controlling the release profiles are often unclear. We have fabricated uniform rhodamine- and piroxicam-containing microspheres, 10 to 100 microm in diameter, to better understand how microsphere size controls drug release. METHODS: Drug distribution within the microspheres was examined using confocal fluorescence microscopy. The rate of polymer degradation was determined as the change in molecular weight, measured by gel permeation chromatography, during in vitro degradation experiments. Further, changes in the surface and interior morphology of the particles during in vitro degradation were investigated by scanning electron microscopy. RESULTS: Microsphere size greatly affected drug distribution. Small (approximately 10-microm) microspheres showed an essentially uniform drug distribution. Larger (approximately 100-microm) microspheres showed redistribution of drug to specific regions of the microspheres. Rhodamine partitioned to the surface and piroxicam partitioned to the interior of large PLG microspheres. Further, the rate of polymer degradation increased with microsphere size, possibly the result of a more acidic interior caused by increased accumulation of hydrolyzed polymer products in larger particles. Finally, larger microspheres developed a more porous interior structure during the drug release. CONCLUSION: Microsphere size affects drug release not only through changes in diffusion rates but also through secondary effects including drug distribution in the particle, polymer degradation rate, and microsphere erosion rates.

Lactic Acid↗

PubMed2002

Precise control of PLG microsphere size provides enhanced control of drug release rate.

An important limitation in the development of biodegradable polymer microspheres for controlled-release drug delivery applications has been the difficulty of specifically designing systems exhibiting precisely controlled release rates. Because microparticle size is a primary determinant of drug release, we developed a methodology for controlling release kinetics employing monodisperse poly(D,L-lactide-co-glycolide) (PLG) microspheres. We fabricated 20-, 40- and 65-microm diameter rhodamine-containing microspheres and 10-, 50- and 100-microm diameter piroxicam-containing microspheres at various loadings from 1 to 20%. In vitro release kinetics were determined for each preparation. Drug release depended strongly on microsphere diameter with 10- and 20-microm particles exhibiting concave-downward release profiles while larger particles resulted in sigmoidal release profiles. Overall, the rate of release decreased and the duration increased with increasing microsphere size. Release kinetics from mixtures of uniform microspheres corresponded to mass-weighted averages of the individual microsphere release kinetics. Appropriate mixtures of uniform microspheres were identified that provided constant (zero-order) release of rhodamine and piroxicam for 8 and 14 days, respectively. Mixing of uniform microspheres, as well as control of microsphere size distribution, may provide an improved methodology to tailor small-molecule drug-release kinetics from simple, biodegradable-polymer microparticles.

Biocompatible Materials↗