Tufts College

Tulane Educational Fund

Simatech Incorporation

Xiaoqin Wang

David L Kaplan

Gary G Leisk

Jon Kluge

Tuna Yucel

Michael L Lovett

Fiorenzo G Omenetto

Jian Liu

Vijay Thomas John

Monica A Serban

Noshir Pesika

Shenzhou Lu

Cheng Qian

Rubo Zheng

Jianbing Wu

Zhaozhu Zheng

Shaozhe Guo

Fuxin Shi

Provided herein relates to methods and compositions for preparing a silk microsphere and the resulting silk microsphere. In some embodiments, the methods and compositions described herein are all aqueous, which can be used for encapsulating an active agent in a silk microsphere, while maintaining activity of the active agent during processing. In some embodiments, the resulting silk microsphere can be used for sustained delivery of an active agent encapsulated therein.

Methods and compositions for preparing a silk microsphere

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 &#x3b2;-sheet structure dominant silk microsphere structures having about 2 &#x3bc;m in diameter. The therapeutic agent can be entrapped in the silk microspheres and used in pharmaceutical formulations for controlled-release treatments.

Silk microspheres for encapsulation and controlled release

Provided herein relates to compositions and methods for lubrication of a surface. The surface amenable to the compositions and methods described herein can be a non-biological surface, a biological surface, or a combination thereof. In some embodiments, the composition comprising a phospholipid-coated silk microsphere can be used for lubrication of a surface. In some embodiments, the composition comprising a phospholipid-coated silk microsphere can be used for joint lubrication, e.g., for treatment of joint disorders such as arthritis.

Silk microspheres and methods for surface lubrication

The invention discloses a freeze-dried powder of high molecular weight silk fibroin, preparation process and use thereof. The freeze-dried powder is obtained from silk by degumming, dissolution, dialysis, centrifugation, high temperature and high pressure treatment and freeze-drying. A method of preparing silk fibroin microspheres with polyethylene glycol comprises mixing a silk fibroin solution of 1-30 wt % with a PEG solution of 10-60 w % and incubating the resulting solution. A controlled-release or sustained-release silk fibroin gel formulation includes a gel-state carrier and a drug dispersed/adsorbed therein, the carrier is a silk fibroin gel formed by blending with LMW-PEG. The freeze-dried powder will not change the native molecular weight and random coil structure of silk fibroin, and can be rapidly dissolved into a solution, and can be stored and transported for a long time, and this reduces waste of silk fibroin materials and promotes R & D and biomedical applications of silk fibroin biomaterials.

Freeze-dried powder of high molecular weight silk fibroin, preparation method therefor and use thereof

The present invention provides for compositions and methods for preparing aqueous insoluble, ductile, flexible silk fibroin films. The silk films comprise silk fibroin and about 10% to about 50% (w/w) glycerol, and are prepared by entirely aqueous processes. The ductile silk film may be further treated by extracting the glycerol from and re-drying the silk film. Active agents may be embedded in or deposited on the glycerol modified silk film for a variety of medical applications. The films may be shaped into 3-dimensional structures, or placed on support surfaces as labels or coatings. The glycerol modified silk films of the present invention are useful in variety of applications such as tissue engineering, medical devices or implants, drug delivery, and edible pharmaceutical or food labels.

Modified silk films containing glycerol

The present invention is directed to silk-based drug delivery compositions for controlled, sustained delivery of therapeutic agent(s) as well as methods of making and using the same.

Silk reservoirs for drug delivery

The present invention provides for methods of preparing silk nanoparticles and microparticles, methods of encapsulating an active agent into the silk nano- and microparticles and compositions comprising these silk particles. In particular, the silk spheres are prepared from phase separation of silk and polyvinyl alcohol (PVA), without exposure to an organic solvent. The method employs a chemical, PVA, which is an FDA-approved ingredient in drug formulations. Different parameters can be adjusted to control the size and shape of the silk spheres during the fabrication process. The silk particle compositions of the present invention may also encapsulate active agents or chemicals. Such compositions allow the active agents to be controllably and sustainably released to the target organs or tissues. The silk composition entrapping active agents also provides for a long-term storage medium for the active agents so entrapped. The silk nano- and microparticles of the present invention are thus suitable for a variety of biomedical and pharmaceutical applications, such as drug delivery or tissue engineering.

Silk nanospheres and microspheres and methods of making same

This invention provides for a process of rapidly forming silk fibroin gelation through ultrasonication. Under the appropriate conditions, gelation can be controlled to occur within two hours after the ultrasonication treatment. Biological materials, including viable cells, or therapeutic agents can be encapsulated in the hydrogels formed from the process and be used as delivery vehicles.

Method for silk fibroin gelation using sonication

The present invention provides for methods of preparing silk nanoparticles and microparticles, methods of encapsulating an active agent into the silk nano- and microparticles and compositions comprising these silk particles.

The present invention provides for compositions and methods of linking silk fibroin to active agents through the specific interaction between avidin and biotin, providing for functionalization of silk-based protein biomaterials. An avidin- or biotin-modified silk is a biomaterial platform for functionalization with a variety of correspondingly linked active agents, such as antibodies and growth factors. A variety of functionalized silk materials, such as silk hydrogel, silk micro/nanoparticles and silk films, can be prepared by the methods of the present invention. The functionalization strategies of the present invention are relatively easy, fast and feasible, and are thus useful in many biomedical applications.

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Winchester, MA, United States of America

Xiaoqin Wang