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Methods for producing multilayered particles, fibers and sprays and methods for administering the same

a multi-layered particle and fiber technology, applied in the direction of microcapsules, chemical/physical processes, drug compositions, etc., can solve the problems of insufficient tumor distribution or therapeutic agents, and infallible breast cancer early detection. , to achieve the effect of low and acceptable levels, less manufacturing steps, and cost-effective

Inactive Publication Date: 2008-08-07
TERAPIA CELULAR LN
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

This approach enables the production of capsules with a wider size range, reduced chemical degradation, and improved cost-effectiveness, facilitating targeted delivery and minimizing adverse effects while maximizing treatment and imaging efficacy for malignancies.

Problems solved by technology

Although imaging and early diagnostic tools have been improving over the past two decades, current breast cancer early detection is far from infallible, especially when using mammograms in younger women.
While magnetic resonance imaging (MRI and ultrasound) and laser-based imaging techniques have been used or evaluated, the issue for best possible contrast between healthy and cancerous tissue for any imagining technique is a longstanding one.
A current challenge facing scientists is determining how to design a therapeutic or an imaging agent and its vehicle, vector or carrier in order to maximize treatment and imaging of malignant cancers in patients while minimizing the adverse effects of treatment.
Moreover, the selective delivery of therapeutic agents to a desired part of the body is also a nontrivial issue.
Current treatments may lead to insufficient tumor distribution or therapeutic agents and often cause adverse effects on patients.
Systemic injections of therapeutic agents carry consequences associated with their nonspecific dispersion in the body and have a limited therapeutic agent distribution throughout the targeted malignancy.
Although emulsion-polymerization methods are relatively scalable, there are several limitations associated with the methods, such as the inability to encapsulate the targets in a quantitative manner, and the high-shear production of emulsions may compromise the integrity of mechanically delicate encapsulates, such as biological constituents such as proteins, genetic material, and other molecules of biological origin.
Although DC coaxial electrospray may be relatively gentle to biological encapsulates, its major limitation is that it lacks simplicity in equipment, design, scalability, and thus cost effectiveness.
One disadvantage of AC electrospray is that it produces undesirablely large particles having sizes well above one micron.
AC electrospray derived particles are unacceptably large.
This may cause the compound two-fluid jet to no longer experience progressive thinning, but an oscillatory thinning and thickening regime which may eventually lead to jet breakup into a droplet-in-droplet regime, or compound electrospray regime.
Although coaxial two-capillary systems may be employed to produce the core-shell structures, described above, there are several disadvantages associated with the conventional systems.
In particular, when a direct, parallel scale-up of the process to increase process throughput is attempted a micro-fabrication problem occurs.
With modern micro-fabrication techniques such challenge may be met, however, these techniques are very complex and not cost effective.
This is the reason why, for example, fabricating a parallel scaled up production of a desired core-shell structure is difficult and expensive.
If there is variability in diameter from inner or outer capillary of one two-capillary coaxial fixture to another in excess of about 2% or 3%, it is not possible to produce a desired core-shell structure without the occurrence of undesirable structures.
With such prior art two-capillary fixture, small differences in the overall pressure drop profiles of the inner and outer capillaries also causes undesirable effects.

Method used

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  • Methods for producing multilayered particles, fibers and sprays and methods for administering the same
  • Methods for producing multilayered particles, fibers and sprays and methods for administering the same
  • Methods for producing multilayered particles, fibers and sprays and methods for administering the same

Examples

Experimental program
Comparison scheme
Effect test

specific example 1

[0156] This example described an encapsulation of a protein solution using a modification of the shell formulation that consisted of a solution of bovine serum albumin (BSA) in the presence of salts such as phosphates to stabilize the pH of the solution. Confocal fluorescence microscopy (CFM) and BSA with a fluorescent tag was used for visualizing the capsule. About 2 mg fluorescent protein was dissolved in about 1 mL of phosphate-buffer saline (PBS), type buffer that stabilized the acid-base properties of this aqueous solution to a pH equal to about 7.4.

[0157] The final BSA concentration was adjusted to about 3 μM. Silica sol was used as the shell fluid precursor following the sol aging procedures, with addition of tert-amyl alcohol to a 50:50 volume ratio.

[0158] In general, for solution aging purposes, an acidified tetraethyl orthosilicate solution in ethanol may be aged at about 80° C. for about 4 to about 6 hours. Ter-amyl alcohol was added to increase the hydrophobicity of th...

specific example 2

[0160] The sol-gel methods and process variables used to encapsulate fluorescent BSA in Specific Example 1 were slightly modified to encapsulate a transaminase. This enzyme was used to catalyze the following reaction:

D.L glutamine+glyoxylic acid→L-glutamine (left unreacted)+α-keto derivative (from D-glutamine)-glycine

[0161] Each enantiomeric from has the ability to rotate polarized light, and a technique known as polarimetry may be used to follow chemical reactions in involving enantiomers as a function of time. The reactants, on the left hand side of the reaction shown above, are basically a mixture with no optical activity, since the D,L prefix stands for about a 50:50 mixture of the D and L enantiomers of glutamine. The products, on the right hand side of the reaction shown above, become enriched in unreacted L-glutamine with a concomitant time-dependent optical rotation signal that may be tracked by polarimetry, because this particular transaminase only catalyzes reactions invo...

specific example 3

particles with 3.1 LACZ as DNA Marker

[0164] The therapeutic solution was prepared by mixing 3.1 LACZ in about 10 mM Bis-Tris propane buffer aqueous solution containing about 1 wt % of isopropanol and about 2 mM of CaCl2. The final concentration of 3.1 LACZ was 700 μg / mL. A biopolymer solution was prepared by mixing two functionalized biopolymers in chloroform: (a) COOH-poly(ethylene glycol)-b-polylactide, or PEG-b-PLA, with a molecular weight of 2000-b-1940 Da using same nomenclature, respectively, and a Mw / Mn=1.2; and (b) Poly(caprolactone)-SH, or PCSH, with a molecular weight of 5,000 Da and a Mw / Mn=1.5. This solution was doped with a solution of magnetite particles with an average diameter of about 15 nm. The weight percent contents of PEG-b-PLA, PCSH, and magnetite particles in this solution were about 0.071 wt %, about 0.058 wt %, and about 0.004 wt % respectively.

[0165] The therapeutic and biopolymer solutions were mixed and dimethyl sulfoxide, or DMSO, was added to form a h...

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Abstract

Capsules and particles with at least one encapsulated and / or entrapped agent, such as therapeutic agent, imaging agents, and other constituents may be produced by electrohydrodynamic processes. More particularly, the agent encapsulated in a vehicle, capsule, particle, vector, or carrier may maximize treatment and / or imaging of malignant cancers while minimizing the adverse effects of treatment and / or imaging.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims priority to and the benefit of U.S. Provisional Application Ser. No. 60 / 746,311, filed May 3, 2006, and U.S. Provisional Application Ser. No. 60 / 886,225, filed Jan. 23, 2007, the disclosures of which are expressly incorporated herein by reference in their entirety.BACKGROUND [0002] 1. Field of Invention [0003] The invention relates to systems and methods for producing capsules and particles with at least one encapsulated and / or entrapped agent, such as therapeutic agent, imaging agents, and other constituents. More particularly, the agent encapsulated in a vehicle, capsule, particle, vector, or carrier may maximize treatment and / or imaging of malignancy while minimizing the adverse effects of treatment and / or imaging. [0004] 2. Related Art [0005] Cancer is a class of diseases or disorders characterized by uncontrolled division of cells and the ability of these to spread, either by direct growth into adjacent tiss...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K51/12A61K49/18A61K9/127A61P35/00B01J13/02
CPCA61K9/5094B05B7/061A61K9/5146A61K9/5192A61K47/48107A61K47/48269A61K47/48276A61K47/48561A61K47/48869A61K49/0043A61K49/0047A61K49/0056A61K49/0065A61K49/0093A61K49/1878A61K51/1244B01J13/04B82Y5/00B05B5/0255A61K9/5115A61K47/551A61K47/642A61K47/6425A61K47/6849A61K47/6925A61P35/00A61P35/02
Inventor LARSEN, GUSTAVOSPRETZ, RUBENVELARDE-ORTIZ, RAFFETVU, DAVIDNUNEZ, LUIS
Owner TERAPIA CELULAR LN