Simultaneously Manufactured Nano-In-Micro (SIMANIM) Particles for Dry-Powder Modified-Release Delivery of Antibodies

作者：Kaye Richard S; Purewal Tol S; Alpar H Oya^*

来源：Journal of Pharmaceutical Sciences, 2009, 98(11): 4055-4068.

DOI：10.1002/jps.21673

• antibody
• inhaled
• microparticles
• nanoparticles
• pulmonary drug delivery
• protein delivery
• spray drying
• poly(lactic/glycolic) acid (PLGA)
• aerosol

Simultaneously Manufactured Nano-In-Micro (SIMANIM) particles for the pulmonary delivery of antibodies have been prepared by the spray-drying of a double-emulsion containing human IgG (as a model antibody), lactose, poly(lactide-coglycolide) (PLGA) and dipalmitoylphosphatidylcholine (DPPC). The one-step drying process involved producing microparticles of a diameter suitable for inhalation that upon contact with aqueous media, partially dissolved to form nanoparticles, similar to 10-fold smaller than their original diameter. Continuous release of the model antibody was observed for 35 days in pH 2.5 release media, and released antibody was shown to be stable and active by gel electrophoresis, field-flow fractionation and enzyme linked immunosorbent assay. Adding 1% L-leucine to the emulsion formulation, and blending 'SIMANIM' particles with 1% magnesium stearate, achieved a fine particle fraction of similar to 60%, when aerosolised from a simple, capsule-based, dry powder inhaler device. 'SIMANIM' particles could be beneficial for the delivery of antibodies targeted against inhaled pathogens or other extracellular antigens, as well as having potential applications in the delivery of a wide range of other biopharmaceuticals and certain small-molecule drugs.

• 出版日期2009-11