Development and testing of particulate formulations for the nasal delivery of antibodies.

Therapeutic antibodies offer a potential treatment for, or means of protection against, airborne infections. For this application, it may be desirable to deliver the antibody directly into the nasal cavity, one of its potential sites of action, since this would be more efficient and convenient than systemic administration. Formulations of a model antibody (human IgG) were developed using albumin, sodium chloride and disaccharides. A combination of these excipients allowed the efficient spray-drying (yield>70%) of the antibody into a microparticulate (1-15 microm) dry powder that was rapidly soluble in aqueous media. The water content and crystallinity of the formulations were also measured, with both properties being affected by the substitution of some of the sodium chloride in the formulation, with lactose. The antibody was found to be stable following the formulation process, as determined by gel-electrophoresis, field-flow-fractionation and enzyme-linked immunosorbent assay. Incubation of an in vitro epithelial cell line in the presence of solutions of the formulations (at concentrations of up to 2500 microg/mL) was found not affect cell viability. The aerosolisation properties of the formulations were tested using Bespak's "Unidose-DP", dry-powder nasal device. The powder aerosol was analysed by laser diffraction, high-speed video and dose deposition in Bespak's nasal cast model. For the latter experiment, a range of additional excipients were either dissolved in the spray-drying liquid feed (leucine), or blended with the spray-dried powder formulation (magnesium stearate, Aerosil and lactose). The major dose deposition site of the standard spray-dried formulation was the nasal vestibule (approximately 55%). The addition of leucine and Aerosil resulted in a 10% increase in the deposition beyond the nasal vestibule, with approximately 45% of the delivered dose being deposited in the turbinates, olfactory region, and nasal-pharynx.

Simultaneously manufactured nano-in-micro (SIMANIM) particles for dry-powder modified-release delivery of antibodies.

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-co-glycolide) (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, approximately 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 approximately 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.