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Researchers at Tufts University have developed novel methods for fabricating nano- and micro-particles from silk. These biocompatible, biodegradable particles are formed under aqueous, ambient conditions and can be used to encapsulate drugs or other bioactive agents. This technology has a multitude of biomedical and pharmaceutical applications, including drug delivery/stabilization and tissue engineering.

Background

        Micro- and nano-particulate systems have been used widely in various biomedical and pharmaceutical applications, such as drug delivery. Depending on the delivery route and disease site, either microspheres or nanospheres provide suitable delivery systems. For example, nanospheres can be designed as short-acting delivery vehicles and used to induce efficient drug accumulation at a target site, for example, to target a tumor in cancerous tissues. Microspheres can be used as depot drug carriers for long-acting delivery. For example, microvesicles may be used for tissue regeneration by releasing growth factors in a polymeric scaffold.

        Synthetic materials, such as biodegradable synthetic polymers, have been used to fabricate micro- and nano-particulate delivery systems. Many of these polymers, however, have inherent limitations for tissue engineering and drug delivery applications. For example, organic solvent is usually needed to dissolve these polymers because of their hydrophobic nature, and the organic solvent may be detrimental to the proteins or other active agents to be loaded in/on the particles. Moreover, the degradation products of many of these polymers are acidic, which may cause the denaturation of proteinaceous or other acid-sensitive drugs. Hence, there remains a need for active agents and processes that provide for microspheres and nanospheres with controllable sphere size and shape, and that avoid using organic solvents and other harsh conditions during the fabrication process.

Invention

        The present invention provides methods of preparing silk nanoparticles and microparticles, methods of encapsulating an active agent into the silk nanoparticles and microparticles, and compositions comprising these silk particles. In particular, water- insoluble silk spheres may be prepared from dissolving silk/ polyvinyl alcohol (PVA) blend films in an aqueous solution, without exposure to an organic solvent at any stage in production. PVA is an FDA-approved ingredient in drug formulations. Different parameters can be adjusted to control the size and shape of the silk micro- and nanoparticles during the fabrication process. The silk micro- and nanoparticle compositions may also comprise silk spheres encapsulating an active agent(s) or chemical(s), and such compositions allow the active agents to be controllably and sustainably released to target cells, organs, or tissues. The fabrication methods are thus easy, safe, controllable, time and energy efficient, and drug-amenable. The silk nanospheres and microspheres are suitable for a variety of biomedical and pharmaceutical applications, such as drug delivery systems, long-term storage/stabilization of sensitive compounds, and tissue engineering.

Advantages

Silk is a revolutionary material that can outperform plastics, inorganic polymers, foams, and glass and add unforeseen functions to technologies where conventional materials are used.

- It is the strongest natural fiber available

- It is biocompatible, with controllable biodegradability

- It has insulating properties comparable to the best ceramics

- It is >99 percent transparent across the visible spectrum

- It can be manufactured in a variety of shapes and sizes

Intellectual Property

US Patents 8,715,740 and 9,381,164; Several Issued Patents in Europe, Israel and Japan

Inventors

David L. Kaplan, Ph.D., Xiaoqin Wang, Ph.D., Tufts University School of Engineering

Tufts reference # T001595

Licensing Contact

Martin Son
martin.son@tufts.edu