Design and evaluation of poly (DL-lactic-co-glycolic acid) nanocomposite particles containing salmon calcitonin for inhalation

TY - JOUR

T1 - Design and evaluation of poly (DL-lactic-co-glycolic acid) nanocomposite particles containing salmon calcitonin for inhalation

AU - Yang, Mingshi

AU - Yamamoto, Hiromitsu

AU - Kurashima, Homare

AU - Takeuchi, Hirofumi

AU - Yokoyama, Toyokazu

AU - Tsujimoto, Hiroyuki

AU - Kawashima, Yoshiaki

PY - 2012/8/15

Y1 - 2012/8/15

N2 - Salmon calcitonin, for the treatment of calcium homeostasis and bone remodeling, was used as a model peptide drug and adsorbed on the surface of biodegradable polymeric poly(dl-lactic-co-glycolic acid) (PLGA) nanospheres. Subsequently, the nanospheres were treated using lyophilizer and loaded onto inhalable carrier using Mechanofusion™ to obtain nanocomposite particles suitable for inhalation. The physicochemical properties and in vitro inhalation properties of the nanocomposite particles were investigated. The pulmonary distribution and pharmacological effect were also evaluated in male Wistar rats. The results showed that the drug loading efficiency of salmon calcitonin on PLGA nanospheres were exceeding 96% (w/w). Inhalation efficiency of the lyophilized PLGA nanospheres was largely improved after they were loaded on the surface of inhalable carrier. Over 50% (w/w) of the lyophilized PLGA nanospheres could be deposited in the alveoli section after intratracheal administration to male Wistar rats, while a rapid elimination rate of the lyophilized nanospheres from the lung was found in pulmonary distribution study. The in vivo pharmacological study showed that the nanocomposite particles exhibited superior hypocalcemic action over salmon calcitonion solution and the lyophilized nanospheres. It suggested that the Mechanofusion™ technique can impart improved inhalation properties to the lyophilized nanospheres for pulmonary delivery of therapeutic peptide drugs.

AB - Salmon calcitonin, for the treatment of calcium homeostasis and bone remodeling, was used as a model peptide drug and adsorbed on the surface of biodegradable polymeric poly(dl-lactic-co-glycolic acid) (PLGA) nanospheres. Subsequently, the nanospheres were treated using lyophilizer and loaded onto inhalable carrier using Mechanofusion™ to obtain nanocomposite particles suitable for inhalation. The physicochemical properties and in vitro inhalation properties of the nanocomposite particles were investigated. The pulmonary distribution and pharmacological effect were also evaluated in male Wistar rats. The results showed that the drug loading efficiency of salmon calcitonin on PLGA nanospheres were exceeding 96% (w/w). Inhalation efficiency of the lyophilized PLGA nanospheres was largely improved after they were loaded on the surface of inhalable carrier. Over 50% (w/w) of the lyophilized PLGA nanospheres could be deposited in the alveoli section after intratracheal administration to male Wistar rats, while a rapid elimination rate of the lyophilized nanospheres from the lung was found in pulmonary distribution study. The in vivo pharmacological study showed that the nanocomposite particles exhibited superior hypocalcemic action over salmon calcitonion solution and the lyophilized nanospheres. It suggested that the Mechanofusion™ technique can impart improved inhalation properties to the lyophilized nanospheres for pulmonary delivery of therapeutic peptide drugs.

U2 - 10.1016/j.ejps.2012.02.024

DO - 10.1016/j.ejps.2012.02.024

M3 - Journal article

C2 - 22414702

SN - 0928-0987

VL - 46

SP - 374

EP - 380

JO - Norvegica Pharmaceutica Acta

JF - Norvegica Pharmaceutica Acta

IS - 5

ER -