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Silk microspheres for encapsulation and controlled release

a microsphere and fibroblast technology, applied in the field of encapsulation and controlled release of microspheres, can solve the problems of reducing the usefulness of encapsulation vehicles for many of the smaller drug molecules, affecting the biological activity of incorporated protein drugs in the polymer matrix, and affecting the biological activity of incorporated protein drugs

Inactive Publication Date: 2010-02-04
TRUSTEES OF TUFTS COLLEGE TUFTS UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, preservation of biological activity of incorporated protein drugs in a polymer matrix and control of subsequent release remain major challenges.
Silk microspheres can be fabricated using physical methods such as spray-drying, however, harsh conditions such as high temperature have prohibited their uses as a protein drug delivery carrier.
In addition, conventional microspheres typically have a large size (above 100 μm), making them less useful as encapsulation vehicles for many of the smaller drug molecules.

Method used

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  • Silk microspheres for encapsulation and controlled release
  • Silk microspheres for encapsulation and controlled release
  • Silk microspheres for encapsulation and controlled release

Examples

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Materials

[0063]Cocoons of B. mori silkworm silk were supplied by M. Tsukada (Institute of Sericulture, Tsukuba, Japan). 1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-(carboxyfluorescein) (fluorescein-DOPE) were purchased from Avanti Polar Lipids (Alabaster, Ala.). 5-(Aminoacetamido)fluorescein (fluoresceinyl glycine amide) was purchased from Molecular Probes (Carlsbad, Calif.). Rhodamine β isothiocyanate-Dextran (M.W. 40,000 Da), horseradish peroxidase (HRP), β-galactosidase, and other chemicals were obtained from Sigma Aldrich (St. Louis, Mo.). 3,3′5,5′ Tetramethylbenzidine (TMB) solution was purchased from BioFX laboratories (Owing Mills, Md.). 1-Ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (EDC), N-hydroxysuccinimide (NHS), and hydroxylamine hydrochloride were purchased from Pierce Biotechnology (Rockford, Ill.). All other chemicals were purchased from Sigma-Aldrich (St. Louis, Mo.).

Purification and Fluorescent La...

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Abstract

A method was developed to prepare silk fibroin microspheres using lipid vesicles as templates to efficiently load therapeutic agents in active form for controlled release. The lipids are subsequently removed through the use of a dehydration agent, such as methanol or sodium chloride, resulting in β-sheet structure dominant silk microsphere structures having about 2 μm in diameter. The therapeutic agent can be entrapped in the silk microspheres and used in pharmaceutical formulations for controlled-release treatments.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims benefit of U.S. provisional application No. 60 / 847,100, filed Sep. 26, 2006, the content of which is incorporated herein by reference in its entirety.GOVERNMENT SUPPORT[0002]This invention was supported by the NIH under an Osteochondral Plug Grant No. NIDCR. The Government has certain rights to the invention.FIELD OF INVENTION[0003]This invention relates to silk fibroin microspheres prepared by mixing silk fibroin with lipids to form microspheres capable of encapsulating therapeutic drugs and releasing the drugs in a controlled manner.BACKGROUND OF INVENTION[0004]Controlled drug release involves a combination of a polymer matrix with bioactive drugs such that the drugs can be delivered in a predictable manner. Polymeric materials, including biodegradable synthetic polymers such as poly(D,L-lactide-co-glycolide) (PLGA) and natural polymer such as collagen and alginate have been used as drug delivery matrices. These ...

Claims

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Application Information

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IPC IPC(8): A61K9/14A61K38/02A61K31/7088A61K39/395A61K38/43A61K38/16A61K38/21A61K38/20A61K38/28
CPCA61K9/127A61K9/1658A61K9/19A61K47/34A61K38/44A61K9/5052A61K9/16A61K31/7076A61K47/42
Inventor KAPLAN, DAVID L.WANG, XIAOQIN
Owner TRUSTEES OF TUFTS COLLEGE TUFTS UNIV
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