Title:  Particles incorporating surfactants for pulmonary drug delivery

United States Patent:  RE37,053

Assignee:  Massachusetts Institute of Technology (Cambridge, MA)

Filed:  July 12, 1999

Improved aerodynamically light particles for drug delivery to the pulmonary system, and methods for their synthesis and administration are provided. In a preferred embodiment, the aerodynamically light particles are made of a biodegradable material and have a tap density less than 0.4 g/cm³ and a mass mean diameter between 5 .mu.m and 30 .mu.m. The particles may be formed of biodegradable materials such as biodegradable polymers. For example, the particles may be formed of a functionalized polyester graft copolymer consisting of a linear .alpha.-hydroxy-acid polyester backbone having at least one amino acid group incorporated therein and at least one poly(amino acid) side chain extending from an amino acid group in the polyester backbone. In one embodiment, aerodynamically light particles having a large mean diameter, for example greater than 5 .mu.m, can be used for enhanced delivery of a therapeutic agent to the alveolar region of the lung. The aerodynamically light particles incorporating a therapeutic agent may be effectively aerosolized for administration to the respiratory tract to permit systemic or local delivery of wide variety of therapeutic agents.

SUMMARY OF THE INVENTION

Particles incorporating surfactants for drug delivery to the pulmonary system, and methods for their synthesis and administration are provided. Exemplary surfactants include naturally occurring phsophatidylcholines, such as dipalmitoylphosphatidylcholine ("DPPC"). In a preferred embodiment, the particles are aerodynamically light particles, which are made of a biodegradable material, and have a tap density less than 0.4 g/cm³, as described in U.S. Ser. No. .[.08/655,570,.]. .Iadd.08/739,308, .Iaddend.filed Oct. 29, 1996, the disclosure of which is incorporated herein. The aerodynamically light particles generally have a mean diameter between 5 .mu.m and 30 .mu.m. The particles may be formed of biodegradable materials such as biodegradable polymers, proteins, or other water soluble or non-water soluble materials. Other examples include particles formed of water-soluble excipients, such as trehalose or lactose, or proteins, such as lysozyme or insulin. The particles incorporating a surfactant can be used for enhanced delivery of a therapeutic agent to the airways or the alveolar region of the lung. The particles may be effectively aerosolized for administration to the respiratory tract to permit systemic or local delivery of a wide variety of therapeutic agents. They also optionally may be co-delivered with larger carrier particles, not carrying a therapeutic agent, having, for example, a mean diameter ranging between about 50 .mu.m and 100 .mu.m.

Claim 1 of 33 Claims

What is claimed is:

1. A particulate composition for drug delivery to the pulmonary system comprising:

biodegradable particles incorporating a therapeutic, prophylactic or diagnostic agent and a surfactant, wherein the particles have a tap density less than 0.4 g/cm³ and a mean diameter between 5 .mu.m and 30 .mu.m effective to yield an aerodynamic diameter of the particles of between approximately one and three microns.

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