Compositions and methods for biodegradable microspheres as carriers of bioactive substances - Patents

Compositions and methods for biodegradable microspheres as carriers of bioactive substances

Agent: Gardere Wynne Sewell LLP Intellectual Property Section - Dallas, TX, US
Inventors: Timothy W. King, Charles W. Patrick
Class: 424490000 (USPTO), A61K009/16 (Intl Class)
#20050255165
11/17/05
A cost-effective, scalable technique for producing microspheres loaded with biologically active solid proteins is provided. The microspheres degrade over time and release biologically active VEGF, as demonstrated by the proliferation of HUVECs in vitro compared to negative controls. A defined concentration of microspheres can deliver a quantifiable level of VEGF with known release kinetics. The invention can be used with other growth factors and applied to tissue engineering applications such as the regeneration of peripheral nerve, bone, adipose tissue, and solid organs. The method of the invention includes the steps of dissolving a polymer with an organic solvent to produce a polymer solution; adding a biologically effective amount of a bioactive substance to the solution to produce a mixture of the polymer and the bioactive substance; vibrating the mixture to produce a bioactive substance-polymer complex; emulsifying the mixture to produce an emulsion comprising the bioactive substance-polymer complex; and extracting the organic solvent from the emulsion to produce microspheres comprising the polymer-bioactive substance complex, wherein the bioactivity of the bioactive substance is usefully preserved.
FIELD OF THE INVENTION
[0001] The present invention relates generally to the field of microencapsulation and, in particular, to compositions and methods for the fabrication of biodegradable microspheres and their use as delivery vehicles for bioactive substances such as solid proteins.
SUMMARY OF THE INVENTION
[0009] The present invention solves the problems in the prior art just described by providing a solid-encapsulation/single-emulsion/ solvent extraction technique to encapsulate solid proteins and other bioactive substances into biodegradable microspheres. The present invention provides a cost-effective, scalable technique for producing microspheres loaded with biologically active proteins, and in particular solid proteins, together with compositions of such microspheres.
[0010] One method for making microspheres of the present invention that encapsulate and effect the controlled release of a bioactive substance includes the steps of dissolving a polymer with an organic solvent to produce a polymer solution, adding a biologically effective amount of a bioactive substance to the solution to produce a mixture of the polymer and the bioactive substance, vibrating the mixture to produce a bioactive substance-polymer complex, emulsifying the mixture to produce an emulsion of the bioactive substance-polymer complex and the organic solvent, and extracting the organic solvent from the emulsion to produce microspheres comprising the polymer-bioactive substance complex, so that the bioactivity of the bioactive substance is usefully preserved.
[0011] The present invention provides a system for delivering a therapeutic agent to tissue. The system includes biodegradable microspheres made as described above and encapsulating a therapeutic agent as the bioactive substance in a dispenser for administration of the microspheres to the tissue so that the microspheres release the therapeutic agent from the microspheres to the tissue.
[0012] The present invention further provides a drug delivery system. The drug delivery system includes biodegradable microspheres incorporating a drug made as previously described and a dispenser for administration of the microspheres. The release of the therapeutic agent or the drug from the microspheres occurs in two phases: an initial burst phase and a later steady-state phase.
[0013] In addition to methods and systems, the present invention provides microsphere compositions. Microspheres of the present invention contain bioactive substances such as polypeptides, therapeutic agents or drugs. A particular feature of the present compositions is that bioactive substances in their solid state, not dissolved in solution, may be contained in the microspheres with the bioactivity of the substance preserved. Another feature of the present invention is that solid bioactive substances are incorporated into microspheres without using the atomization-freeze process familiar to those skilled in the art. Further, the present invention does not make use of a tissue homogenizer or an ultrasonic atomizer.
Complete article is available online.