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. 2020 Mar 13;25(6):1311.
doi: 10.3390/molecules25061311.

Design and Characterizations of Inhalable Poly(lactic- co-glycolic acid) Microspheres Prepared by the Fine Droplet Drying Process for a Sustained Effect of Salmon Calcitonin

Hideyuki Sato  1 , Aiko Tabata  1 , Tatsuru Moritani  2 , Tadahiko Morinaga  2 , Takahiro Mizumoto  3 , Yoshiki Seto  1 , Satomi Onoue  1
Affiliations

Design and Characterizations of Inhalable Poly(lactic- co-glycolic acid) Microspheres Prepared by the Fine Droplet Drying Process for a Sustained Effect of Salmon Calcitonin

Hideyuki Sato et al. Molecules. .

Erratum in

Abstract

The present study aimed to develop inhalable poly (lactic-co-glycolic acid) (PLGA)-based microparticles of salmon calcitonin (sCT) for sustained pharmacological action by the fine droplet drying (FDD) process, a novel powderization technique employing printing technologies. PLGA was selected as a biodegradable carrier polymer for sustained-release particles of sCT (sCT/SR), and physicochemical characterizations of sCT/SR were conducted. To estimate the in vivo efficacy of the sCT/SR respirable powder (sCT/SR-RP), plasma calcium levels were measured after intratracheal administration in rats. The particle size of sCT/SR was 3.6 µm, and the SPAN factor, one of the parameters to present the uniformity of particle size distribution, was calculated to be 0.65. In the evaluation of the conformational structure of sCT, no significant changes were observed in sCT/SR even after the FDD process. The drug release from sCT/SR showed a biphasic pattern with an initial burst and slow diffusion in simulated lung fluid. sCT/SR-RP showed fine inhalation performance, as evidenced by a fine particle fraction value of 28% in the cascade impactor analysis. After the insufflation of sCT samples (40 µg-sCT/kg) in rats, sCT/SR-RP could enhance and prolong the hypocalcemic action of sCT possibly due to the sustained release and pulmonary absorption of sCT. From these observations, the strategic application of the FDD process could be efficacious to provide PLGA-based inhalable formulations of sCT, as well as other therapeutic peptides, to enhance their biopharmaceutical potentials.

Keywords: dry powder inhaler; fine droplet drying process; poly(lactic-co-glycolic acid); salmon calcitonin; sustained release.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Appearance and particle size distribution of sustained-release particles of salmon calcitonin (sCT/SR) prepared with the fine droplet drying (FDD) process. Solid line, frequency; dotted line, cumulative undersize fraction curve. White bar represents 10 µm.
Figure 2
Figure 2
Changes in secondary structure of sCT during FDD process. (A) Circular dichroism (CD) spectrum of fresh sCT solution (solid line) and extracted sCT solution from sCT/SR (dotted line). (B) ThT binding assay of sCT samples. The aggregated sCT in diluted solutions were detected by the thioflavin T binding assay. Non-aged sCT, and sCT/SR were dissolved in 20 mM PBS (pH 7.4). *, p < 0.05; and **, p < 0.01 vs. non-aged sCT. Each bar represents mean ± SE of 3 independent experiments.
Figure 3
Figure 3
In vitro release behavior of sCT from PLGA microparticles in simulated lung fluid. ●, sCT powder; and ○, sCT/SR. Each bar represents mean ± SE of 3 independent experiments.
Figure 4
Figure 4
Appearance and in vitro inhalation property of sCT/SR-respirable powder (RP). (A) Scanning electron microscopic image of sCT/SR-RP. White bar represents 25 µm. (B) Deposition pattern of sCT/SR-RP in Andersen cascade impactor (C, capsule; and A, adapter). The analysis was conducted using a Jet haler® with an airflow rate of 28.3 L/min. The fine particle fraction (FPF) value of sCT/SR-RP was calculated using the ratio of total drug deposited in stage 2 and lower (white bars).
Figure 5
Figure 5
Hypocalcemic action of sCT after the intratracheal administration of sCT samples in rats (40 µg-sCT/kg, i.t.). (A) Time transitions of plasma calcium levels after the administration of sCT samples and (B) AUEC0–24 h of each group. ●, control-RP; ▽, sCT-RP; and □, sCT/SR-RP. Data represent mean ± SE of 4–6 experiments. **, p < 0.01 with respect to the control-RP group.
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