Preparation and evaluation of poly(lactic-co-glycolic acid) microparticles as a carrier for pulmonary delivery of recombinant human interleukin-2: II. In vitro studies on aerodynamic properties of dry powder inhaler formulations

Abstract

Objective: The aim of this study was the preparation and evaluation of dry powder formulations of recombinant human interleukin-2 (rhIL-2)-loaded microparticles to be administered to the lung by inhalation.

Methods: As indicated in our previous study, the microparticles were prepared by modified water-in-oil-in-water (w₁/o/w₃) double emulsion solvent extraction method using poly(lactic-co-glycolic acid) (PLGA) polymers. The dry powder formulations were prepared with blending of microparticles and mannitol as a coarse carrier. The actual aerodynamic characteristics of the microparticles alone and prepared mixtures with mannitol are evaluated by using the eight-stage Andersen cascade impactor.

Results: Due to the low tapped density of microparticles (<0.4 g/cm³), the theoretical aerodynamic diameter (MMADt) values were calculated (<5 μm) on the basis of the geometrical particle diameter and tapped density values. The lowest tapped density value (0.17 g/cm³) belongs to the cyclodextrin-containing formulation. According to the results obtained using the cascade impactor, the emitted doses for all microparticle formulations were found to be rather high and during the aerosolization for all the formulations except F3 and F5, >90% of the capsule content was determined to be released. However, the actual aerodynamic diameter (MMADa) values were seen to be higher than the MMADt values. The blending of the microparticles with mannitol allowed their aerodynamic diameters to decrease and their fine particle fraction values to increase.

Conclusion: The obtained results have shown that the mixing of rhIL-2-loaded microparticles with mannitol possess suitable aerodynamic characteristics to be administered to the lungs by inhalation.

Keywords::

• Dry powder inhalation
• pulmonary drug delivery
• coarse carrier
• mannitol
• interleukin-2
• PLGA microparticles

Acknowledgement

The authors wish to thank the Novartis (Turkey) for providing rhIL-2 (Proleukin).

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.