TY - JOUR
T1 - Budesonide nanocrystal-loaded hyaluronic acid microparticles for inhalation
T2 - In vitro and in vivo evaluation
AU - Liu, Tingting
AU - Han, Meihua
AU - Tian, Fang
AU - Cun, Dongmei
AU - Rantanen, Jukka
AU - Yang, Mingshi
PY - 2018/2/1
Y1 - 2018/2/1
N2 -
Most inhaled pharmaceutical formulations on the market are intended to exert immediate pharmacological action, even although inhaled sustained-release formulations can be needed to reduce the frequency of dosing. The purpose of this study was to investigate the pulmonary retention and pharmacokinetics of a poorly water-soluble drug after loading its nanocrystal form into inhalable mucoadhesive microparticles composed of hyaluronic acid. It was intended to prolong the pharmacological effect without compromising the dissolution rate of the poorly water-soluble drug. In this study, budesonide, a corticosteroid anti-inflammatory drug, was used as a model poorly water-soluble drug. Submicron budesonide particles were prepared by wet ball milling, and subsequently loaded into hyaluronic acid microparticles by the spray drying process. The ball-milled budesonide particles and the spray-dried microparticles were characterized using dynamic light scattering (DLS), laser diffraction, Scanning electron microscopy (SEM), X-ray powder diffraction (XRD) and differential scanning calorimetry (DSC). Selected formulations were evaluated in terms of their dissolution/release rate, aerosol performance, muco-adhesion and pharmacokinetics in rats. As shown by XRD and DSC analysis, the nanonized budesonide particles in this study were mainly in crystalline form. The dissolution/release study showed that the in vitro release of budesonide from the microparticles was not significantly sustained compared with the dissolution rate of budesonide nanocrystals (BUD-NC). However, the budesonide in the microparticles exhibited prolonged retention on the surface of porcine tracheal tube owing to the muco-adhesion ability of hyaluronic acid. After intratracheal administration to rats, the BUD-NC exhibited a similar pharmacokinetic profile to that of budesonide solution via i.v. injection. In contrast, budesonide loaded in the mucoadhesive microparticles exhibited a significantly prolonged T
max
and increased bioavailability with the animal model. This study demonstrated that inhaled microparticles composed of hyaluronic acid could produce sustained budesonide pharmacological effects. This can be attributed to the mucoadhesion of the polymer that overcame the mucociliary clearance and, consequently, prolonged the retention of the active substance in the lung without necessarily reducing the in vitro dissolution rate.
AB -
Most inhaled pharmaceutical formulations on the market are intended to exert immediate pharmacological action, even although inhaled sustained-release formulations can be needed to reduce the frequency of dosing. The purpose of this study was to investigate the pulmonary retention and pharmacokinetics of a poorly water-soluble drug after loading its nanocrystal form into inhalable mucoadhesive microparticles composed of hyaluronic acid. It was intended to prolong the pharmacological effect without compromising the dissolution rate of the poorly water-soluble drug. In this study, budesonide, a corticosteroid anti-inflammatory drug, was used as a model poorly water-soluble drug. Submicron budesonide particles were prepared by wet ball milling, and subsequently loaded into hyaluronic acid microparticles by the spray drying process. The ball-milled budesonide particles and the spray-dried microparticles were characterized using dynamic light scattering (DLS), laser diffraction, Scanning electron microscopy (SEM), X-ray powder diffraction (XRD) and differential scanning calorimetry (DSC). Selected formulations were evaluated in terms of their dissolution/release rate, aerosol performance, muco-adhesion and pharmacokinetics in rats. As shown by XRD and DSC analysis, the nanonized budesonide particles in this study were mainly in crystalline form. The dissolution/release study showed that the in vitro release of budesonide from the microparticles was not significantly sustained compared with the dissolution rate of budesonide nanocrystals (BUD-NC). However, the budesonide in the microparticles exhibited prolonged retention on the surface of porcine tracheal tube owing to the muco-adhesion ability of hyaluronic acid. After intratracheal administration to rats, the BUD-NC exhibited a similar pharmacokinetic profile to that of budesonide solution via i.v. injection. In contrast, budesonide loaded in the mucoadhesive microparticles exhibited a significantly prolonged T
max
and increased bioavailability with the animal model. This study demonstrated that inhaled microparticles composed of hyaluronic acid could produce sustained budesonide pharmacological effects. This can be attributed to the mucoadhesion of the polymer that overcame the mucociliary clearance and, consequently, prolonged the retention of the active substance in the lung without necessarily reducing the in vitro dissolution rate.
KW - Budesonide
KW - Hyaluronic acid
KW - Inhalation
KW - Nanocrystal-embedded microparticles
UR - http://www.scopus.com/inward/record.url?scp=85034788009&partnerID=8YFLogxK
U2 - 10.1016/j.carbpol.2017.11.018
DO - 10.1016/j.carbpol.2017.11.018
M3 - Journal article
C2 - 29253943
AN - SCOPUS:85034788009
VL - 181
SP - 1143
EP - 1152
JO - Carbohydrate Polymers
JF - Carbohydrate Polymers
SN - 0144-8617
ER -