U.S. patent application number 14/965508 was filed with the patent office on 2016-04-07 for systems and methods for facilitating the generation of core-sheath taylor cones in electrospinning.
The applicant listed for this patent is Toby Freyman, John Marini, Robert Mulligan, Quynh Pham, Upma Sharma, Xuri Yan. Invention is credited to Toby Freyman, John Marini, Robert Mulligan, Quynh Pham, Upma Sharma, Xuri Yan.
Application Number | 20160096304 14/965508 |
Document ID | / |
Family ID | 50474676 |
Filed Date | 2016-04-07 |
United States Patent
Application |
20160096304 |
Kind Code |
A1 |
Pham; Quynh ; et
al. |
April 7, 2016 |
SYSTEMS AND METHODS FOR FACILITATING THE GENERATION OF CORE-SHEATH
TAYLOR CONES IN ELECTROSPINNING
Abstract
Systems and methods for electrospinning of core-sheath fibers
are provided. The systems and methods achieve optimization of a
shear stress that exists at a fluid boundary between core and
sheath polymer solutions, by varying certain parameters of an
electrospinning apparatus and/or the solutions used therewith.
Inventors: |
Pham; Quynh; (Methuen,
MA) ; Sharma; Upma; (Somerville, MA) ; Marini;
John; (Weymouth, MA) ; Yan; Xuri; (Brighton,
MA) ; Mulligan; Robert; (Arlington, MA) ;
Freyman; Toby; (Lexington, MA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Pham; Quynh
Sharma; Upma
Marini; John
Yan; Xuri
Mulligan; Robert
Freyman; Toby |
Methuen
Somerville
Weymouth
Brighton
Arlington
Lexington |
MA
MA
MA
MA
MA
MA |
US
US
US
US
US
US |
|
|
Family ID: |
50474676 |
Appl. No.: |
14/965508 |
Filed: |
December 10, 2015 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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14053994 |
Oct 15, 2013 |
9243346 |
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14965508 |
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61713785 |
Oct 15, 2012 |
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61723882 |
Nov 8, 2012 |
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Current U.S.
Class: |
264/465 |
Current CPC
Class: |
B29L 2031/731 20130101;
D01D 5/0038 20130101; D01D 5/0069 20130101; D01D 5/0015 20130101;
D01D 5/34 20130101; B29C 48/05 20190201 |
International
Class: |
B29C 47/00 20060101
B29C047/00 |
Goverment Interests
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
[0002] This invention was made with Government support under
70NANB11H004 awarded by the National Institute of Standards and
Technology. The Government has certain rights in the invention.
Claims
1. A method for electrospinning a core-sheath fiber, comprising the
steps of: providing an electrospinning apparatus comprising a first
vessel having a first elongate aperture, a second vessel having a
second elongate aperture, wherein the first and second elongate
apertures are aligned along a single central axis, and a collector
positioned at a distance from the first and second elongate
apertures; flowing a first flowable material comprising a core
polymer into the first vessel; flowing a second flowable material
comprising a sheath polymer into the second vessel; adjusting a
height of the first vessel and first elongate aperture relative to
the height of the second elongate aperture; and applying an
electric potential between the collector and the first and second
apertures, the electric potential having a magnitude and an
orientation effective to form at least one electrospinning jet,
wherein at least one parameter selected from the group consisting
of a width of the first or second aperture, a length of the first
or second aperture, and a flow rate of the first or second flowable
material is chosen to optimize a shear stress generated at a fluid
interface between the first and second flowable materials during
the application of the potential, such that a desired ratio of core
and sheath polymers is incorporated into the at least one
electrospinning jet.
2. The method of claim 1, wherein the first flowable material exits
the first aperture at a first velocity and the second flowable
material exits the second aperture at a second velocity.
3. The method of claim 2, wherein the second velocity is about 1.3
times greater than the first velocity.
4. The method of claim 2, wherein a ratio of the first velocity to
the second velocity varies during the application of the electric
potential.
5. The method of claim 1, wherein the first aperture has a first
width and the second aperture has a second width.
6. The method of claim 5, wherein the first width is about half of
the second width.
7. The method of claim 1, wherein a length of the first elongate
aperture is equal to a length of the second elongate aperture.
8. The method of claim 1, wherein a length of the first elongate
aperture is less than a length of the second elongate aperture.
9. The method of claim 1, wherein the material ejected from the
first elongate aperture in the at least one electrospinning jet
passes through the second elongate aperture as well.
10. The method of claim 9, wherein the first vessel and the first
elongate aperture are submerged in the second flowable material and
wherein adjusting the height of the first vessel and first elongate
aperture relative to the height of the second elongate aperture
controls the depth at which the first vessel and first elongate
aperture are submerged within the second flowable material in the
second vessel.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to (a) U.S. Provisional
Patent Application No. 61,713,785 by Pham et. al. entitled "Systems
and Methods for Facilitating the Generation of Core-Sheath Taylor
Cones in Electrospinning" filed Oct. 15, 2012, and (b) U.S.
Provisional Patent Application No. 61/723,882 by Pham et al.
entitled "Systems and Methods for Facilitating the Generation of
Core-Sheath Taylor Cones in Electrospinning" filed Nov. 8, 2012.
The entire disclosure of each of the foregoing references is
incorporated by reference herein for all purposes.
TECHNICAL FIELD
[0003] The present invention relates to systems and methods for the
manufacturing of microscale or nanoscale concentrically-layered
fibers by electrospinning, and more particularly to systems and
methods for facilitating the initiation and stabilization of
core-sheath Taylor cones during electrospinning.
[0004] Macro-scale structures formed from concentrically-layered
nanoscale or microscale fibers ("core-sheath fibers") such as
AxioCore.RTM. fibers commercialized by Arsenal Medical (Watertown,
Mass.) are useful in a wide range of applications including drug
delivery, tissue engineering, nanoscale sensors, self-healing
coatings, and filters. On a commercial scale, the most commonly
used techniques for manufacturing core-sheath fibers are extrusion,
fiber spinning, melt blowing, and thermal drawing. None of these
methods, however, are ideally suited to producing drug-loaded
core-sheath fibers, as they all utilize high temperatures which may
be incompatible with thermally labile materials such as drugs or
polypeptides. Additionally, fiber spinning, extrusion and
melt-blowing are most useful in the production of fibers with
diameters greater than ten microns.
[0005] Core-sheath fibers with diameters less than 20 microns can
also be produced by electrospinning, in which an electrostatic
force is applied to a polymer solution, to induce the formation of
electrospinning jets which harden to form very fine fibers.
Conventional electrospinning methods utilize a needle to supply a
polymer solution, which, upon activation of an electric field, is
then ejected into a continuous stream toward a grounded collector.
As the jet stream travels in the air, solvent evaporation occurs
resulting in a single long polymer fiber. Core-sheath fibers have
been produced by electrospinning using coaxial needles, in which
concentric needles are used to eject different polymer solutions:
the innermost needle ejects a solution of the core polymer, while
the outer needle ejects a solution of the sheath polymer.
[0006] Coaxial electrospinning has been used in the fabrication of
core-sheath fibers for drug delivery in which the drug-containing
layer (the "core") is confined to the center of the fiber and is
surrounded by a drug-free layer (the "sheath"). The sheath then
serves as a diffusion barrier to a therapeutic agent in the core.
Thus, release rates of the drug can be tightly controlled by
varying the thickness, composition, and degradation profile of the
sheath material as well as composition and concentration of the
drug in the core. Additionally, core-sheath fibers can be used for
tissue engineering (e.g., incorporation of therapeutics to affect
cell growth), filtration (e.g., by incorporation of self-cleaning
compounds such as titanium dioxide), sensors (e.g., creation of
hollow fibers to allow measurement of small analyte volumes), and
as self-healing materials (e.g., spontaneous repair of surfaces
with release of core contents). Core-sheath fibers can also be used
as a way to create fibers from materials that would be otherwise
unable to be electrospun (e.g., polymer pre-cursors such as
poly(glycerol sebacic acid) or insulating materials such as
Teflon). To do so, the material incompatible with electrospinning
is confined in the center of the fiber and is surrounded by a
material optimized tor electrospinning; upon completion of the
process the surrounding sheath material is removed (e.g., dissolved
or melted away).
[0007] The use of a conventional coaxial needle electrospinning
apparatus is depicted in FIG. 1A. The two concentric needles 110
separately deliver the core and sheath solutions--the core solution
is delivered through the inner needle 112 whereas the sheath
solution is delivered through the outer needle 114. A grounded
collector (not shown) is placed at a distance from the needle, and
a potential is generated between the collector and the concentric
needles 110 with a magnitude and direction sufficient to impel both
solutions from the needles in a continuous stream toward the
grounded collector. Each stream forms a single core-sheath fiber,
so the throughput of coaxial electrospinning methods is inherently
limited by the fact that only one stream can be produced by each
concentric needle pair 110.
[0008] To increase throughput, coaxial nozzle arrays have been
utilized, but such arrays pose their own challenges, as separate
nozzles may require separate pumps, the multiple nozzles may clog,
and interactions between nozzles may lead to heterogeneity among
the fibers collected. Another means of increasing throughput, which
utilizes a spinning drum immersed in a bath of polymer solution,
has been developed by the University of Liberec and commercialized
by Elmarco, S.R.O. under the mark Nanospider.RTM.. The
Nanospider.RTM. improves throughput relative to other
electrospinning methods, but to date core-sheath fibers have not
been fabricated using the Nanospider.RTM..
[0009] A high-throughput approach for generating the core-sheath
fibers, which has beat commercialized by Arsenal Medical
(Watertown, Mass.) (the "Arsenal Electrospinning Technology"),
utilizes a plurality of elongate vessels with narrow apertures or
slits which are aligned to co-localize different materials to
multiple sites that form Taylor cones, thereby promoting the
formation of multiple electrospinning jets and electrospun fibers
with high throughput, as discussed in. e.g., U.S. patent
application Ser. No. 13/362,467, filed on Jan. 31,2012 (U.S. Patent
App. Pub. No. 2012/0193836). the entire disclosure of which is
hereby incorporated by reference.
[0010] FIG. 1B depicts an apparatus 120 implementing the Arsenal
Electrospinning Technology. The apparatus 120 includes an elongate
vessel 22 having one or more elongate apertures or slits 124
extending along at least a portion of the vessel 122; each slit
surface includes one or more slits 126. A positive terminal of a
power supply (not shown) is connected to the elongate vessel 122
directly or via a wire such that a potential difference exists
between the elongate vessel 122 and a grounded collector 128. Upon
application of a voltage, the core polymer solution 130 becomes
charged; the charged polymer solution is acted upon by an
electrostatic force impelling the core polymer solution 130 away
from the elongate vessel 122 that counteracts the surface tension
thereof. When the applied voltage is above a critical threshold
value, Taylor cones 132 and electrospinning jets (or jets) 134 form
at the exposed slit surfaces; the jets 134 are then attracted
toward the collector 128, thereby forming homogeneous fibers.
[0011] The Arsenal Electrospinning Technology facilitates the
manufacture of core-sheath fibers at high throughput by allowing
significantly larger volumetric flow rates relative to needle-based
systems 132, thus addressing a long-standing need in the field for
efficient, high-throughput production of electrospun core-sheath
fibers. However, further improvements in the efficiency of the
Arsenal Electrospinning Technology could facilitate the use of
core-sheath fibers in many applications, and could potentially
significantly reduce the cost of producing such fibers.
SUMMARY OF THE INVENTION
[0012] The present invention, in its various embodiments, addresses
the ever-present need in the field for increased efficiency in
core-sheath fiber production by providing improved systems and
methods for high-throughput production of electrospun core-sheath
fibers. Embodiments of the invention improve the consistency of
core- and sheath-polymer incorporation into Taylor cones and/or
electrospinning jets and electrospun fibers by optimizing shear
stresses applied at fluid boundaries between core- and
sheath-solutions at sites of Taylor cone initiation.
[0013] In one aspect, the invention relates to a method for forming
an electrospun core-sheath fiber that includes providing an
apparatus that includes first and second vessels defining first and
second elongate apertures, respectively, which are aligned with
one-another. The apparatus also includes a grounded collector at a
distance from the apertures. According to embodiments of the
invention, a first flowable material comprising a core polymer and
a second flowable material comprising a sheath polymer are flowed
into the first and second vessels, then an electrical potential is
created between the apertures and the grounded collector, with
potential sufficient in magnitude and orientation to initiate and
sustain multiple electrospinning jets. The method also includes
optimizing a shear stress generated at a fluid interface such that
a desired ratio of core to sheath polymer is achieved in the
resulting electrospinning jets; this optimization occurs through
the selection of appropriate parameters such as length or width of
the first and/or second apertures and velocity or viscosity of the
first and/or second flowable materials. In various embodiments, the
first flowable material exits the first aperture at a first
velocity, while the second flowable material exits the second
aperture at a second velocity, and the first velocity can be about
1.3 times, 2.25 times or 2.5 times greater than the second
velocity, and may vary during the application of the electrical
potential. In some cases, the first and second elongate apertures
are nested and aligned along a single central axis, and the width
of the first aperture is optionally about half of the width of the
second aperture. The first and second elongate apertures can have
the same length, or they may have different lengths. The first
vessel is optionally nested inside of the second vessel, in which
case the first and second apertures are parallel so that material
that is ejected from the first aperture must also pass through the
second aperture on the way to the collector. The first and second
apertures are in certain embodiments of the method, co-planar,
while in other instances they are offset by about 1 mm, in which
case the first vessel and the first aperture are optionally
submerged in the second flowable material. In some cases, the first
and second flowable materials are characterized by particular
viscosities, and the first flowable material is less viscous than
the second flowable material.
[0014] In another aspect, the invention relates to an apparatus for
high-throughput electrospinning of core-sheath fibers that includes
first and second elongate vessels having first and second elongate
apertures, respectively. The first and second elongate apertures
are aligned about a single central axis, each of the vessels is in
fluid communication with a fluid source that is optionally filled
with first and second flowable materials comprising a core and a
sheath polymer, respectively, and the apparatus includes a
plurality of valves or other control means for providing the first
and/or second flowable materials at predetermined races. In some
cases, the first and second vessels are nested, and the apparatus
includes means for adjusting a height of the first vessel and the
first aperture relative to the second aperture, thereby controlling
the depth at which the first vessel and the first aperture are
submerged within the second flowable material in the second vessel.
In some instances, the first and second vessels are wedge-shaped,
and the elongate apertures are positioned at apexes of the
vessels.
BRIEF DESCRIPTION OF THE DRAWINGS
[0015] Non-limiting embodiments of the present invention will be
described by way of example with reference to the accompanying
figures, which are schematic and are not intended to be drawn to
scale. In the figures, each identical or nearly identical component
illustrated is typically represented by a single numeral. For
purposes of clarity, not every component is labeled in every
figure, nor is every component of each embodiment of the invention
shown where illustration is not necessary to allow those of
ordinary skill in the art to understand the invention, in the
figures:
[0016] FIGS. 1A-1B include schematic illustrations of examples of
electrospinning setups;
[0017] FIG. 2 includes an exemplary schematic illustration of an
embodiment of the invention;
[0018] FIGS. 3A-B include examples of controlling the generation of
core-sheath Taylor cones to facilitate the formation of core-sheath
fibers.
[0019] FIGS. 4A-4D include exemplary schematic illustrations of an
embodiment of the invention wherein flow rates of material to the
core slit and sheath slit surfaces are different to form a
core-sheath fiber.
[0020] FIGS. 5A-C include exemplary schematic illustrations of
embodiments of the invention wherein fixture variables are changed
to form core-sheath fibers, including slit width, core and sheath
flow velocity, and length of core and sheath slits.
[0021] FIGS. 6A-D illustrate some embodiments wherein the sheath
flow rate is higher than the core flow rate.
[0022] FIGS. 7A-D illustrate core sheath fibers as formed by the
embodiments of the invention with a drug core enclosed by a polymer
sheath.
[0023] FIGS. 8A-F illustrate some embodiments where the core
solution flow rates and velocities are varied.
[0024] FIGS. 9A-D illustrate some embodiments of the invention with
different sheath and core slitwidths.
[0025] FIG. 10A includes exemplary schematic illustrations of
embodiments of the invention wherein the depth of the core slit
surface varies relative to the sheath slit surface.
[0026] FIG. 10B shows taylor cones generated in the embodiments
depicted in FIG. 10A.
[0027] FIG. 11 illustrates some embodiments of the invention
wherein material viscosity is varied to form core-sheath
fibers.
[0028] FIG. 12A-D illustrates fibers and patches formed according
to methods of the invention.
DETAILED DESCRIPTION
[0029] FIG. 2 illustrates a top view of one embodiment of a system
that generates core-sheath fibers using a needleless, core-sheath
electrospinning process. The core and sheath solutions are first
delivered to a slit surface; at the slit surface, a fluid meniscus
forms and numerous electrospinning jets may initiate at one or more
slits upon activation of an external electric field. In various
embodiments, controlling the generation of core-sheath Taylor cones
at the fluid meniscus facilitates the formation of core-sheath
fibers. For example, upon generating distinct Taylor cones, as
shown in FIG. 3A, in the needleless electrospinning process,
core-sheath jets and fibers are subsequently created.
[0030] FIG. 4A-4D schematically depict core and sheath polymer
solutions delivered to the core and sheath slits, respectively,
through the respective features using, for example, syringe pumps.
In one embodiment, the flow rate of the sheath solution that fills
the left and right channels is relatively faster than that of the
core solution (FIG. 4A); as the sheath solution from the two
channels merges at the top of the slit surface and bridges the gap
therebetween, a fluid meniscus is created under the force of
surface tension (FIG. 4B). Upon applying a potential voltage to the
slit fixtures, the sheath polymer solution becomes charged; the
induced charges may accumulate on the outer surface of the sheath
solution (FIG. 4C). As a result, sheath jets may be initiated when
a critical potential has been reached. In addition, the pressure of
the internal core fluid at the locations where the sheath solution
jets are formed may drop allowing the core fluid to be pulled by
the applied electric field (FIG. 4C). Because the internal core
solution flows towards locations having a relative lower pressure,
under the shear forces of the sheath solution, a core-sheath Taylor
cone may be generated (FIG. 4D).
[0031] In various embodiments, the formation of the core-sheath
Taylor cones and/or jets is controlled via the manipulation of
various parameters which control the shear stress between the
sheath and core solutions. The shear stress may be varied by
changing the geometry of the slit fixtures, velocities, or
viscosities of the core and/or sheath solutions. For example, if
the flow velocity of the sheath solution is greater than that of
the core solution at the exit point of the slit surfaces, distinct
core-sheath Taylor cones may be formed. The flow velocities of the
solutions depend on the volumetric flow rates and the surface
areas, as given in Equations (1) and (2), where Q.sub.sheath and
Q.sub.core represent the flow rates of the sheath and core
solutions, respectively; d.sub.sheath and d.sub.core are the widths
of the sheath and core slits, respectively, and L.sub.sheath and
L.sub.core are the lengths of the sheath and core slits,
respectively (as shown in FIG. 5). Accordingly, the flow velocities
of the sheath and/or core solutions may be manipulated by changing
the volumetric flow rates and/or the slit geometries thereof.
v total = Q sheath + Q core d sheath .times. L sheath ( 1 ) v core
= Q core d core .times. L core ( 2 ) ##EQU00001##
[0032] In various embodiments, the flow velocities of the sheath
and core solutions are varied based on the variations in the flow
rates thereof while maintaining the slit geometry. In one
embodiment, the slit-fixture is comprised of two triangular shaped
hollow troughs that are aligned to a single vertical plane to form
a one-dimensional slit-surface (FIG. 2) The lengths of the sheath
and core slits are 41 mm and 35 mm, respectively, and the widths of
the sheath and core slits are 2.2 mm and 0.6 mm, respectively.
Referring to Table 1, in one embodiment, the core flow rate is set
constant (e.g., at 20 mL/h) while the sheath flow rate is varied
from 20 mL/h to 200 mL/h to manipulate the formation of the Taylor
cones (Note: The conditions used in this and experiments following
corresponds to flow rates of up to 300 ml/h, resulting in
significantly higher volumetric throughput relative to needle-based
systems). As shown in FIG. 6A-D, the most distinct core-sheath jets
(as visualized by a clear delineation between the core and sheath
solutions in the Taylor cone due to the presence of dexamethasone
in the core) occur for condition A where the sheath flow-rate is
ten times larger than the core flow rate (or the total velocity is
approximately 2.5 times greater than the core velocity); whereas no
distinct core-sheath jets are discernible for condition D where the
sheath flow rate is roughly the same as the core flow rate (or the
total velocity is approximately 2.25 times less than the core
velocity). Accordingly, varying the sheath flow rate and thereby
changing the relative ratio of the sheath solution velocity to core
solution velocity effectively facilitates the formation of the
core-sheath Taylor cones; a higher likelihood of generating the
Taylor cones occurs when a ratio of the sheath flow velocity to the
core flow velocity is larger.
[0033] FIGS. 7A-D depict typical fibers that are produced using the
system described above. The diameter of the fibers are
approximately 2-4 micron, which is within the order of magnitude
expected for electrospun fibers. FIGS. 7A-D also include scanning
electron micrographs of fiber cross-sections illustrating the
encapsulation of dexamethasone within a sheath polymer.
Core Flow Rate
[0034] Referring to Table 2, in another embodiment, the sheath flow
rate is kept constant while the core flow rate is varied.
Specifically, the sheath flow rate was set to 200 ml/h while the
core flow rate was modulated from between 20 to 100 ml/hr. The same
polymer solutions were used, as described previously. Again, when
the sheath flow velocity is greater than the core solution flow
velocity, the core-sheath Taylor cone formation has a higher
probability of being distinct (FIGS. 8A-F). In another embodiment,
the core flow rate was kept constant at 20 ml/hr and the sheath
flow rate was varied from 200 ml/hr (forming a distinct
core-sheath) to 100 ml/hr (forming a distinct core-sheath) to 40
ml/hr (forming a non-distinct core-sheath.
[0035] The core-sheath fiber formation may thus be manipulated by
varying of the flow rates of the sheath and/or core solutions.
Slit Fixture Geometry Core Slit Width
[0036] As shown in Eqs. (1) and (2), the velocities of the core and
sheath solutions depend on the slit fixture geometry (e.g., the
widths and/or lengths of the core and/or sheath slits). In various
embodiments, the lengths of the sheath and core slits (i.e.,
L.sub.sheath and L.sub.core, respectively) are approximately equal
such that the formation of the slits across the entire fixture is
the same in order to reduce the manufacturing complexity. As a
result, the widths of the sheath and core slits are the primary
variables in the slit geometry that may be altered to manipulate
the flow velocities of the solutions. In one embodiment, the width
of the core slit is varied while that of the sheath slit is fixed
at 2.2 mm; the sheath flow rate is set to be constant at 200 ml/h
while the core flow rate is adjusted as listed in Table 3. As
indicated in Eq. (2), the core flow velocity is greater in a
narrower core slit at a given core flow rate also shown in the
shaded squares of Table 3). Because the core-sheath jets are formed
when the velocity of the core solution is smaller than that of the
sheath solution, the maximum core flow rate that may be able to
generate distinct core-sheath Taylor cones for a narrower core slit
is smaller than that of a wider core slit. For example, referring
to Table 3, a core flow rate of 5 mL/h is sufficient for a core
slit having a width of 0.3 mm to form distinct Taylor cones,
whereas a core flow rate of 20 mL/h is required to form distinct
Taylor cones for a core slit having a width of 0.9 mm. The width of
the core slit may further impact the flow of the sheath solution.
For example, utilization of the 0.9 mm-wide core slit may leave
little space for the sheath fluid flowing through the 2.2 mm-wide
sheath slit (because the wall thickness of the core slit may be as
thick as 0.3 mm). Accordingly, in one embodiment, the core slit
width is carefully chosen such that the flow of the sheath fluid is
not impeded.
Sheath Slit Width
[0037] In another embodiment, the width of the sheath slit varies
from 1.5 mm to 3 mm while the width of the core slit is fixed at
0.6 mm and the flow rates of the sheath and core solutions are set
constant at 200 mL/h and 20 ml/h, respectively. Again, because the
core-sheath jets are formed when the velocity of the sheath
solution is larger than that of the core solution, the minimum
sheath flow rate capable of generating distinct core-sheath Taylor
cones for a wider sheath slit is greater than that of a narrower
sheath slit, as shown in Table 4. Note that the velocity of the
sheath solution being greater than that of the core solution is
necessary for formation of the core-sheath Taylor cones; this,
however, may not be the only criteria. For example, a larger
difference between the sheath and core velocities may result in
easier formation of the distinct core-sheath cone and/or jet
structure.
[0038] Theoretically, the maximum electric field (E) attainable for
a wedge shaped conductor depends upon the slit width (d), and wedge
angle (.alpha.), as described by Eq. 3, where V.sub.0 is the
applied voltage and R is a distance above the jet. Equation (3)
indicates that the electric field is inversely proportional to the
width of the slit. Table 5 depicts that a wider sheath slit may
result in lower jet stability at a constant voltage (e.g., 85 kV);
this agrees with the theoretical prediction that the slit geometry
may affect the stability of core-sheath jet induced by the
electrical field. A higher voltage may be required to produce
stable jets when wider slits are employed. Referring to Table 6, in
various embodiments, when a wider sheath slit is used, a higher
voltage is required to generate a larger number of stable jets.
E .about. V 0 R ( R d ) x / .alpha. - 1 ( 3 ) ##EQU00002##
Sheath Slit Width and Core Slit Width
[0039] In various embodiments, the widths of the sheath and core
slit fixtures are both varied, e.g., reduced to 1.5 mm and 0.3 mm,
respectively. The flow rates of the sheath and core solutions may
also be changed such that the flow velocities thereof remain die
same as that of the solutions flowing in slits having larger width
dimensions (e.g., sheath slit width of 2.2 mm and core slit width
of 0.6 mm). For example, as shown in Table 7, the flow rates of the
sheath and core solutions are changed to 140 mL/h and 10 mL/h,
respectively, in the smaller slits (i.e., sheath slit width of 1.5
mm and core slit width of 0.3 mm) to match the flow velocities of
0.68 mm/s and 0.27 mm/s of the sheath and core solutions,
respectively, generated using larger slits (i.e., sheath slit width
of 2.2 mm and core slit width of 0.6 mm) and greater flow rates
(i.e., 200 mL/hr and 20 mL/hr for the sheath and core solutions,
respectively). These results indicate that electrospinning
apparatus design parameters in general, and specifically a smaller
sheath slit area or larger core slit area, can affect the quality
of sheath and/or core solution into Taylor cones and/or electrospun
fibers. Without wishing to be bound by any theory, it is believed
that modifying the relative areas of the core and/or sheath slits
can result in higher sheath velocities relative to core velocities
for a given core or sheath flow rate. This in turn enables the
formation of core-sheath fibers where the core flow rate is higher
and, therefore, the core makes up a larger proportion of the fiber
for elcctrosprayed particle) cross-sectional area, diameter or
volume. Again, the formation of the core-sheath Taylor cones occurs
when the total velocity is relatively greater than the core
velocity; this is applicable to slit fixtures having various slit
widths (FIGS. 9A-D). Note that Taylor cones are not observable for
condition D of Table 7, even though the sheath flow rate is much
greater than the core flow rate; this again indicates that it is
the velocity difference, not the flow rate difference, between the
core and sheath solutions that controls the formation of the
cote-sheath fibers.
Core Slit Height
[0040] Referring to FIG. 10A, in some embodiments, the height
spacing between the apex of the core and sheath slit fixtures
varies from 1 mm to 6 mm. Using sheath and core flow rates of 200
and 20 ml/h, respectively, and an applied voltage of 75 kV, a
larger spacing resulted in less distinct core-sheath Taylor cones,
as shown in FIG. 10B; this indicates that an optimal core and
sheath slit spacing exists that benefits the shear forces applied
on the core fluid by the sheath fluid to produce successful viscous
entrainment.
Viscosities of the Solutions
[0041] Variations in the fluid properties (e.g., viscosity) of the
core and/or sheath solutions may result in significant changes to
the shear stress, thereby affecting the formation of the
core-sheath Taylor cones. In various embodiments, the viscosity of
the sheath solution is varied, for example, by adjusting the weight
percentage of PCL solution. Referring to Table the viscosity of the
sheath solution changes from approximately 280 cP to 760 cP when
the PCL content in 6:1 (by vol) CHCl.sub.3:MeOH is changed from 12
wt % (system C) to 16 wt % (system D), respectively; the viscosity
of the core solution is fixed at roughly 500 cP in both systems. In
one implementation, the core flow rate varies from 5 mL/hr to 20
mL/hr and the flow rate of the sheath solution is kept constant at
200 mL/h. As shown in FIG. 11, at the same flow rate conditions,
the core-sheath formation and morphology of the Taylor cones is
more distinct when the viscosity of the sheath solution is larger
than that of the core solution (system D). Again, generation of the
distinct Taylor cones is facilitated in the systems having a larger
viscosity of the sheath solution compared with that of the core
solution. Accordingly, generation of the Taylor cones and formation
of the fibers may be manipulated via both flow velocities and fluid
viscosities of the solutions. Note that although the viscosity of
the sheath solution is tuned by adjusting the weight percentage of
PCL, one of ordinary skill in the art will understand that the
viscosity of the sheath and/or core solution may be adjusted using
other approaches, such as heating and cooling of the solutions or
utilization of polymers having different molecular weights.
Core Sheath Fiber Applications
[0042] The invention described herein can be used to manufacture
any type of core sheath structure that is traditionally fabricated
via a needle setup. Broadly speaking, core-sheath electrospinning
is employed in situations to: (1) create bicomponent fibers: (2) to
encapsulate a particle; (3) to create fibers from traditionally
unelectrospinnable materials; (4) to create hollow fibers. These
types of fibers have applications in a variety of fields including
drug delivery, tissue engineering, diagnostics, electronics, energy
storage, textiles, etc.
[0043] Bicomponent fibers fabricated using core-sheath
electrospinning contain a core material that is different than the
sheath material. This is desirable in instances where it is desired
to combine the properties of two different types of polymers into a
single fiber. These properties can be mechanical, chemical,
biological, degradation, solubility, etc. in nature. For example, a
core-sheath fiber consisting of PCL as the core and collagen as the
sheath relies on the PCL component to impart mechanical integrity
to the fiber while the collagen (being biological) imparts
biocompatibility when implanted in vivo. Another example is
bicomponent fibers with different solubility characteristics
wherein either the core or the sheath acts as a sacrificial layer
(this method can also be used to create hollow fibers--see below).
In another example, bicomponent fibers with piezoelectric
properties can be made with PVDF sheath and an intrinsically
conductive polymer core. Alternatively, the bicomponent fibers can
consist of a solid sheath but contain a non-solid core (e.g.
liquid). In another embodiment, the components of the sheath and
the core in the biocomponent fiber can react during electrospinning
or after fibers have formed. Bicomponent fibers are also useful in
situations whereby cost of materials is an issue. For example, less
expensive material can be used in the core while a more expensive
material is used in the sheath. This allows less sheath material to
be used, thus conserving costs. Another example is bicomponent
fibers having a biodegradable core material (e.g., PLGA in
hexafluoroisopropanol electrospun at a flow rate of 40 ml/hr) and a
biostable sheath material (e.g., nylon 6,6 in hexafluoroisopropanol
electrospun at a flow rate of 200 ml/hr), as shown in FIG. 14.
[0044] Core-sheath fibers can be used to encapsulate any particle,
either in dissolved or particulate form. Any number of particles,
biologic, organic, organometallic, ceramic, and inorganic compounds
can theoretically be encapsulated and include but are not limited
to the following: small molecule chemicals, proteins, fluorophores,
metals, hydrides, microparticles, plastics, carbon black, carbon
nanotubes, graphene, flutopolymers (e.g.:Teflon), liposomes,
etc.
[0045] Using core-sheath electrospinning, materials that are
traditionally unelectrospinnable can be co-electrospun into fibers
using a polymer that is electrospinnable. The unelectrospinnable
material can exist as a component in the resulting bi-component
fiber system or the electrospinnable material can be removed after
fiber fabrication, leaving behind only the unelectrospinnable
material. The unelectrospinnable material can either be in the
sheath or the core. Depending on the unelectrospinnable material
can be used to coat a core carrier polymer, as described below with
Teflon AF. Examples of unelectrospinnable materials include resins,
latent curatives, phase change materials, certain inherently
conducting polymers, solgels, Teflon AF, and prepolymers and
thermosetting polymers that require cross-linking such as PGS, PPF,
PLCL, PGCL, PDMS, and/or polyurethanes, polyesters, polyimides,
epoxies, and the like. An example in which the unelectrospinnable
material is the sheath is with Teflon AF. Teflon AF by itself is
unelectrospinnable due to low conductivity of the solution;
however, using a core carrier polymer such as PCL, core sheath
fibers can be fabricated that consist of the core polymer being
coated by the Teflon AF. In other instances, the unelectrospinnable
material is incorporated into the core. For example, a core-sheath
fiber that consists of a prepolymer in the core. Once the fibers
are formed, the fiber is subjected to the curing step (e.g. heat,
UV, etc), that results in the prepolymer cross-linking and becoming
solid. The sheath material can then be removed if desired, to leave
behind the core polymer as a fiber. An example of this is with
PDMS, which can be electrospun in the core with a polymer sheath.
After fabrication, the fibers can then be exposed to heat allowing
for the PDMS to cure and harden, forming a bicomponent fiber of
PDMS and sheath polymer. The polymer sheath can then be removed if
desired (e.g. by dipping in solvent), to leave behind PDMS fibers.
In an alternate embodiment, the unelectrospinnable material can be
used to influence the formation and resulting quality of the fibers
that are produced. For example, an unelectrospinnable salt solution
can be used as the sheath in order to help drive down the fiber
diameter of the core polymer that is electrospun. In an example of
using the present invention to electrospin materials that are
traditionally unelectrospinnable, a core-sheath fiber was made with
a sheath polymer system of 3.5 w t% 85/15 PLGA in 6:1 (by volume)
chloroform:methanol, and a core polymer of PDMS (Sylgard 184, a
two-part liquid system consisting of a pre-polymer and a
cross-linking agent mixed in a 10:1 mass ratio), as shown in FIG.
12C. The sheath and core solution flow rates were 200 ml/hr and 20
ml/hr. respectively. The fibers were spun into a mesh approximately
1 mm in thickness, which was placed in an over at 100.degree. C.
for three hours. To optionally yield a homogeneous fiber (i.e., a
fiber that is not core-sheath, but instead a single cross-sectional
structure) as shown in FIG. 17, the mesh was immersed in chloroform
for one hour to allow the PLGA sheath to dissolve to yield PDMS
fibers. In alternative embodiments of forming PDMS fibers,
water-soluble polymers such as PEO, PVA, gelatin or dextran are
used for the sheath material, which is removed from the electrospun
fibers using aqueous means. In other alternative embodiments, other
two-part PDMS systems can be cured by exposure to UV light or
cross-linked into elastomers through free radical, condensation, or
other reactions; or one-pan PDMS can be used that cure upon
exposure to moisture in the atmosphere or upon photocuring. In
other alternative embodiments, the sheath is removed by degradation
instead of solvent dissolution, or is etched away using an acid or
other etchant, or if sufficiently brittle, is mechanically
disrupted to fracture and separate the sheath from the core.
[0046] Core-sheath fibers can be used to create hollow fibers.
Hollow fibers can be efficient as air filled fibers for clothing
insulation. As well, the temporary nature of the core can allow for
sufficient reinforcement of the material for weaving or
post-processing and upon removal, leave behind ultralight but
strong fabrics. Biomedical, electronic, optical, sensing, energy
storage, and catalysis applications, for example) can utilize
hollow fibers, which have excellent insulative properties. Hollow
fibers can allow for better nutrient and gas exchange for tissue
engineering applications. Hollow fibers can be created using oil as
the core and after fabrication, removal of the oil by extraction in
solvents such as octane or hexane. Hollow ceramic (e.g,, SiO2,
SnO2, Al2O3, ZnO and TiO2) fibers via sot-gels of their alkoxide
precursors can also be electrospun into hollow fibers.
Alternatively, hollow fibers can also be created by using a water
soluble or biodegradable polymer in the core and a non-water
soluble or biostable polymer as the sheath. Subsequent extraction
in water or exposure in vivo will remove the aqueous-soluble core.
In general, hollow fibers can be created from core-sheath fibers in
which the core material dissolves in the extraction solvent,
whereas the sheath material does not. An example of this concept
was carried out using 2 wt % polyethylene oxide (PEO) in 6:1 (by
volume) chloroform:acetonitrile as the core material and 3.5 wt %
PLGA in hexafluoroisopropanol as the sheath material. The sheath
flow rate was 200 ml/hr while the core flow rate was 20 ml/hr,
using the slit-surface needleless electrospinning system. The
water-soluble PEO core was subsequently dissolved to yield a hollow
PLGA fiber, as shown in FIG. 12B. In other example, PLGA is used
for the core material and nylon in the sheath, followed by the use
of chloroform to dissolve the PLGA to yield hollow nylon
fibers.
[0047] The systems and methods described herein can be modified to
novel electrospun or electrosprayed articles. In one example, the
polymer solutions described above are diluted, such that
core-sheath micro or nanoparticles are generated at high throughput
by electrospraying. In another example, the core and/or sheath
solutions supplied to an electrospinning apparatus are generated by
melting, rather than dissolving, a polymer composition. In still
another example, different core and/or sheath solutions are
delivered to different segments along the length of the slit,
thereby forming, in a single apparatus, at least two different
fiber types characterized by different core and/or sheath
compositions, and facilitating the generation of higher-order
structures such as yarns, ropes, or patches that incorporate the
different fiber types.
[0048] Other embodiments include a sheath material with a lower
melting point than the core material such that heating a mesh of
electrospun fibers results in melting of the sheath material (but
not the core material) at the fiber cross-over points in the mesh
without compromising the integrity of the overall mesh.
[0049] Still other embodiments make use of a sheath material that
has the ability to absorb or repel water of other fluids while the
core material provides mechanical integrity.
[0050] The systems and methods described above are used, in some
instances, to create very small (nm) diameter-sized fibers, which
are otherwise difficult to produce. This can be achieved, for
example, by having a high sheath flow rate relative to the core
flow rate, resulting in a core-sheath fiber with a very small core.
Upon sacrificial removal of the sheath layer, the small core filler
remains.
[0051] The fibers of the present invention have numerous
applications in medicine. For example, fibers and meshes of the
present invention can be used as supports for rotator cuff repair
or similar orthopedic applications at the tissue/suture interface;
as protein microarrays with low limits of detection due to
increased surface area with fibers; as novel hydrophobic filters
that are thermostable; as water-repellant but breathable
lightweight fabric; as medical bandages for burns or wounds that
allow gas exchange and exudates to fill the porosity therein; as
tissue engineering scaffolds; as drug delivery vehicles; as sensors
and diagnostic elements; as self-healing coatings; as filter
elements; as textiles; in clean tech applications; and in numerous
other medical and non-medical applications.
[0052] The fibers of the present invention may be fabricated by a
wide range of polymeric materials, as described herein. Examples
not previously identified include a core-sheath fiber structure
formed from a sheath material of 85/15 L-PLGA in
chloroform:methanol and a core material of 70/30 PCL/dexamethasone
in chloroform:methanol (where PCL is polycaprolactone, and the core
material may or may not include a therapeutic agent); sheath
materials of 12 wt % PCL and 16 wt % PCL in chloroform:methanol and
a core material of 12 wt % PCL in 6:1 (by volume)
chloroform:methanol containing 30 wt % dexamethasone relative to
PCL.
Advantages of the Invention as it Relates to High Throughput
Open-Bath Monofiber Fabrication Systems
[0053] Current high throughput methods to create mono fibers
utilize a rotating drum or wire bundle mostly immersed in an open
bath of polymer solution, or free surface electrospinning. The
operation requires that the solution have an optimal viscosity and
surface tension such that solution can be drawn up onto the surface
of the drum or wire as it rotates. The open nature of the bath
solution results in an inherent limitation in which solvent
evaporation occurs, resulting in the polymer solution becoming more
viscous over time. The closed-system of the needleless system docs
not have this inherent disadvantage of solvent evaporation. The
requirement of viscosity along with solvent evaporation can
potentially limit the versatility of polymer/solvent systems that
can be electrospun using these methods. For example, certain
solvent/polymers potentially cannot be electrospun because the
evaporation rate is too quick or they do not impart rheological
properties amenable to being drawn up onto the drum surface.
[0054] The solution viscosity that works with open bath free
surface electrospinning systems are relatively lower than that used
with the needleless fixture described herein. Thus, electrospinning
of polymer suspensions will be more difficult, due to more settling
of the particles in less viscous solutions. It is also less likely
that a particle with weight can be dragged up onto the surface of
the rolling drum. Additionally, our needleless setup is capable of
electrospraying solutions.
[0055] Another advantage of our system relative to the open bath
free surface system is that there is no material waste because all
of the polymer solution can be pushed through the slit fixture and
electrospun into fibers. This is not possible in the case of open
bath systems, which requires the rotating mandrel to be rotating in
a bath of solution in order for fibers to be formed. Therefore,
there will always be material that is not consumed. Moreover, the
efficiency of solution consumption of the disclosed invention
relative to the open bath system should be greater in the
needleless fixture. The amount of solution-material that is
consumed (electrospun) per unit of time using the drum and open
bath is relatively less than the amount that can be consumed in the
same amount of time via the needleless fixture described herein,
since only a thin layer of solution is drawn up during each
rotation and not all of the solution is electrospun.
[0056] The operation of the open bath free surface electrospinning
requires that spinning and subsequent fiber collection occurs
upwards. Our system is capable of electrospinning and fiber
collection in any direction. For example, using our process, fiber
collection can occur upside-down. This can be beneficial in
circumstances in which one would want to collect fibers downwards
towards/into a bath of water for example.
[0057] In electrospinning, each Taylor cone that forms leads to one
long continuous fiber that gets collected. In a typical operation
of the needleless fixture, there are approximately 10 jets that
form along the length of the slit; the collected mesh is therefore
comprised of 10 very long fibers intertwined with one another. In
contrast, during the operation of the open bath free surface
electrospinning, hundreds of jets form and disappear with each
rotation of the drum, thus the resulting mesh consists of thousands
of relatively short fibers. This may result in relatively
mechanically weaker meshes compared to less number of longer fibers
that are intertwined.
[0058] The fibers that are produced using the open bath system
arise from Taylor cones that spontaneously form. Thus, the fiber
diameter is likely to be primarily a function of the solution
properties only. The design of the needleless fixture contains
processing parameters that potentially enable greater control over
fiber diameter. For example, in addition to the solution
properties, solution flow rates can he manipulated to control fiber
diameter size. Furthermore, the number of jets produced can also be
controlled, which could lead to differences in fiber diameter
size.
[0059] Another potential advantage of the needleless invention
described herein relates to maintenance of sterility. The open bath
nature of current high throughput electrospinning methods is more
easily susceptible to contamination front particles or fibers that
are not collected properly. Conversely, the closed system of our
invention mitigates any of these concerns.
[0060] The phrase "and/or," as used herein should be understood to
mean "either or both"of the elements so conjoined, i.e., elements
that are conjunctively present in some cases and disjunctively
present in other cases. Other elements may optionally be present
other than the elements specifically identified by the "and/or"
clause, whether related or unrelated to those elements specifically
identified unless clearly indicated to the contrary. Thus, as a
non-limiting example, a reference to "A and/or B," when used in
conjunction with open-ended language such as "comprising" can
refer, in one embodiment, to A without B (optionally including
elements other than B); in another embodiment, to B without A
(optionally including elements other than A); in yet another
embodiment, to both A and B (optionally including other elements);
etc.
[0061] As used in this specification, the terms "substantially/"
"approximately" or "about"means plus or minus 10% (e.g., by weight
or by volume), and in some embodiments, plus or minus 5%. Reference
throughout this specification to "one example," "an example," "one
embodiment," or "an embodiment" means that a particular feature,
structure, or characteristic described in connection with the
example is included in at least one example of the present
technology. Thus, the occurrences of the phrases "in one example,"
"in an example," "one embodiment," or "an embodiment" in various
places throughout this specification are not necessarily all
referring to the same example. Furthermore, the particular
features, structures, routines, steps, or characteristics may be
combined in any suitable manner in one or more examples of the
technology. The headings provided herein are for convenience only
and are not intended to limit or interpret the scope or meaning of
the claimed technology.
[0062] The term "consists essentially of" means excluding other
materials that contribute to function, unless otherwise defined
herein. Nonetheless, such other materials may be present,
collectively or individually, in trace amounts.
[0063] The terms and expressions employed herein are used as terms
and expressions of description and not of limitation, and there is
no intention, in the use of such terms and expressions, of
excluding any equivalents of the features shown and described or
portions thereof. In addition, having described certain embodiments
of the invention, it will be apparent to those of ordinary skill in
the art that other embodiments incorporating the concepts disclosed
herein may be used without departing from the spirit and scope of
the invention. Accordingly, the described embodiments are to be
considered in all respects as only illustrative and not
restrictive.
TABLE-US-00001 TABLE 1 Variation of the flow rate of the sheath
solution Total velocity Distinct Sheath Core greater Core-Sheath
Flow Flow Total Core than Taylor Con- Rate Rate velocity Velocity
Core Cones dition (ml/h) (ml/h) (mm/s) (mm/s) Velocity? Formed? A
200 20 0.68 0.27 Yes Yes B 100 20 0.37 0.27 Yes Yes C 40 20 0.19
0.27 No No D 20 20 0.12 0.27 No No
TABLE-US-00002 TABLE 2 Variation of the flow rate of the core
solution Total velocity Distinct Sheath Core greater Core-Sheath
Flow Flow Total Core than Taylor Con- Rate Rate velocity Velocity
Core Cones dition (ml/h) (ml/h) (mm/s) (mm/s) Velocity? Formed? A
200 20 0.68 0.27 Yes Yes B 200 30 0.71 0.40 Yes Yes C 200 40 0.74
0.53 Yes Yes D 200 60 0.80 0.80 No No E 200 80 0.86 1.06 No No F
200 100 0.92 1.32 No No
TABLE-US-00003 TABLE 3 Variation of the width of the core slit
##STR00001##
TABLE-US-00004 TABLE 4 Variation of the width of the sheath slit
Core Slit Width 0.6 mm Sheath Slit Width 1.5 mm 2.2 mm 3.0 mm
Solution Flow Rates (ml/h) 200:20 200:20 200:20 300:20 Total
velocity (mm/s) 1 0.68 0.5 0.72 Core Velocity (mm/s) 0.26 0.26 0.26
0.26 Total velocity > Core Velocity Yes Yes Yes Yes Quality of
core/sheath Taylor Distinct Distinct Not Distinct cone Distinct
TABLE-US-00005 TABLE 5 Jet stability at different sheath slit
widths (V = 85 kV throughout) Core Slit Width 0.6 mm Sheath Slit
Width 1.5 mm 2.2 mm 3.0 mm Solution Flow Rates (ml/h) 100:20 100:20
100:20 Jet Stability High High Low
TABLE-US-00006 TABLE 6 Jet number at different sheath slit width
Sheath Sheath Sheath Sheath core Slit = 1.5 mm Slit = 2.2 mm Slit =
3.0 mm flow 40/20 100/20 ml/ 40/20 100/20 ml/ 40/20 100/20 ml/
rates ml/hour hour ml/hour hour ml/hour hour 90 kV 13 jets 11 jets
-- -- 85 kV 11 jets 11 jets 8 jets 8-9 jets 6 jets 4-6 jets 75 kV
10 jets 9 jets 8 jets 8-9 jets -- 2 jets 70 kV 9 jets -- -- -- --
-- 65 kV 8 jets -- 8 jets 7-8 jets -- --
TABLE-US-00007 TABLE 7 Flow rates and calculated velocities of slit
fixtures having small widths Sheath Distinct Core- Flow Core Flow
Total Core Total velocity Sheath Taylor Rate Rate velocity Velocity
greater than Cones Condition (ml/h) (ml/h) (mm/s) (mm/s) Core
Velocity? Formed? A 140 10 0.68 0.27 Yes Yes B 142 15 0.71 0.40 Yes
Yes C 144 20 0.74 0.53 Yes Yes D 147 30 0.80 0.80 No No
TABLE-US-00008 TABLE 8 Polymer solutions and their viscosities
System Solution Viscosity (cP) C - Sheath 12 wt % PCL in
CHCl.sub.3:MeOH (6:1 280 vol:vol) D - Sheath 16 wt % PCL in
CHCl.sub.3:MeOH (6:1 760 vol:vol) Core solution 12 wt % PCL in
CHCl.sub.3:MeOH (6:1 500 for both systems vol:vol), 30%
Dexamethasone loading relative to polymer mass in core solution
* * * * *