TY - JOUR
T1 - Engineered sodium hyaluronate respirable dry powders for pulmonary drug delivery
AU - Martinelli, Francesco
AU - Balducci, Anna Giulia
AU - Kumar, Abhinav
AU - Sonvico, Fabio
AU - Forbes, Ben
AU - Bettini, Ruggero
AU - Buttini, Francesca
PY - 2017/1/30
Y1 - 2017/1/30
N2 - Sodium hyaluronate (HYA) warrants attention as a material for inhalation due to its (i) therapeutic potential, (ii) utility as a formulation excipient or drug carrier, and (iii) ability to target lung inflammation and cancer. This study aimed to overcome formulation and manufacturing impediments to engineer biocompatible spray-dried HYA powders for inhalation. Novel methodology was developed to produce HYA microparticles by spray drying. Different types of surfactant were included in the formulation to improve powder respirability, which was evaluated in vitro using cascade impactors. The individual formulation components and formulated products were evaluated for their biocompatibility with A549 respiratory epithelial cells. The inclusion of stearyl surfactants, 5% w/v, produced the most respirable HYA-powders; FPF 59.0–66.3%. A trend to marginally higher respirability was observed for powders containing stearylamine > stearyl alcohol > cetostearyl alcohol. Pure HYA was biocompatible with A549 cells at all concentrations measured, but the biocompatibility of the stearyl surfactants (based on lethal concentration 50%; LC50) in the MTT assay ranked stearyl alcohol > cetostearyl alcohol > stearylamine with LC50 of 24.7, 13.2 and 1.8 μg/mL, respectively. We report the first respirable HYA powders produced by spray-drying. A lead formulation containing 5% stearyl alcohol was identified for further studies aimed at translating the proposed benefits of inhaled HYA into safe and clinically effective HYA products.
AB - Sodium hyaluronate (HYA) warrants attention as a material for inhalation due to its (i) therapeutic potential, (ii) utility as a formulation excipient or drug carrier, and (iii) ability to target lung inflammation and cancer. This study aimed to overcome formulation and manufacturing impediments to engineer biocompatible spray-dried HYA powders for inhalation. Novel methodology was developed to produce HYA microparticles by spray drying. Different types of surfactant were included in the formulation to improve powder respirability, which was evaluated in vitro using cascade impactors. The individual formulation components and formulated products were evaluated for their biocompatibility with A549 respiratory epithelial cells. The inclusion of stearyl surfactants, 5% w/v, produced the most respirable HYA-powders; FPF 59.0–66.3%. A trend to marginally higher respirability was observed for powders containing stearylamine > stearyl alcohol > cetostearyl alcohol. Pure HYA was biocompatible with A549 cells at all concentrations measured, but the biocompatibility of the stearyl surfactants (based on lethal concentration 50%; LC50) in the MTT assay ranked stearyl alcohol > cetostearyl alcohol > stearylamine with LC50 of 24.7, 13.2 and 1.8 μg/mL, respectively. We report the first respirable HYA powders produced by spray-drying. A lead formulation containing 5% stearyl alcohol was identified for further studies aimed at translating the proposed benefits of inhaled HYA into safe and clinically effective HYA products.
KW - Hyaluronic acid
KW - hyaluronan
KW - inhalation toxicology
KW - dry powder inhaler
KW - particle engineering
UR - http://www.scopus.com/inward/record.url?scp=85006893037&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2016.12.002
DO - 10.1016/j.ijpharm.2016.12.002
M3 - Article
SN - 0378-5173
VL - 517
SP - 286
EP - 295
JO - INTERNATIONAL JOURNAL OF PHARMACEUTICS
JF - INTERNATIONAL JOURNAL OF PHARMACEUTICS
IS - 1-2
ER -
