چکیده (انگلیسی):

The purpose of this research was to develop liposomal dry
powder aerosols for protein delivery. The delivery of stable
protein formulations is essential for protein subunit vaccine
delivery, which requires local delivery to macrophages in the
lungs. β-Glucuronidase (GUS) was used as a model protein
to evaluate dry powder liposomes as inhaled delivery vehicles.
Dimyristoyl phosphatylcholine:cholesterol (7:3) was
selected as the liposome composition. The lyophilization
of liposomes, micronization of the powders, aerosolization
using a dry powder inhaler (DPI), and in vitro aerodynamic
fine particle fraction upon collection in a twinstage
liquid impinger were evaluated. After lyophilization
and jet-milling, the total amount of GUS and its activity,
representing encapsulation efficiency and stability, were
evaluated. The GUS amount and activity were measured
and compared with freshly-prepared liposomes in the presence
of mannitol, 43% of initial GUS amount, 29% of
GUS activity after lyophilization and 36% of GUS amount,
22% of activity after micronization were obtained. Emitted
doses from dry powder inhaler were 53%, 58%, 66%,
and 73% for liposome powder:mannitol carrier ratios of
1:0, 1:4, 1:9, and 1:19. Fifteen percent of the liposome
particles were less than 6.4 μm in aerodynamic diameter.
The results demonstrate that milled liposome powders
containing protein molecules can be aerosolized effectively
at a fixed flow rate. Influences of different cryoprotectants
on lyophilization of protein liposome formulations are reported.
The feasibility of using liposomal dry powder
aerosols for protein delivery has been demonstrated but
further optimization is required in the context of specific
therapeutic proteins.