Pulmonary delivery of scutellarin solution and mucoadhesive particles in rats.
The objectives of this study were to investigate the effects of mucoadhesive excipients on systemic bioavailability of an inhaled drug and to evaluate the feasibility of using the pulmonary route for non-invasive systemic delivery of scutellarin, a poorly orally absorbed flavonoid glucuronide. Following intratracheal spray of the scutellarin solution, the bioavailability was found to be approximately 77% in rats, which was >30-fold higher than that via the peroral route. In addition, the pulmonary absorption of scutellarin appeared to avoid the intestinal first-pass metabolism accompanied by peroral administration. Spray-dried scutellarin particles with the presence of mucoadhesive excipients were found to affect the corresponding mucociliary transport rate (MTR) as evaluated by a frog palate model. The pharmacokinetic results indicated that the magnitude of AUC(0-480) of intrapulmonary delivered drug particles was not correlated to the fine particle fraction (FPF) but inversely related to the MTR. Incorporating mucoadhesive polymeric mixtures into the scutellarin particles, the MTR decreased by sixfold, and the absolute bioavailability of the drug was found to increase from 70.1% to 97.9% despite a decrease in the FPF. Moreover, in vitro results evaluated using Calu-3 and A549 cell lines showed that scutellarin and spray-dried particles with or without the presence of mucoadhesives exhibited no local cell cytotoxic effects in the tested concentration range. In conclusion, the conducting airway is well permeable to scutellarin, and scutellarin may be effectively delivered systemically through inhalation of respirable droplets or particles.
Liu
Xiao-Bin
XB
Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
Ye
Jun-Xiao
JX
Quan
Li-Hui
LH
Liu
Chun-Yu
CY
Deng
Xu-Liang
XL
Yang
Ming
M
Liao
Yong-Hong
YH
D000268:Adhesiveness; D000280:Administration, Inhalation; D000284:Administration, Oral; D000336:Aerosols; D000818:Animals; D047310:Apigenin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D001682:Biological Availability; D002025:Bufonidae; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D005079:Excipients / Q000737:chemistry* / Q000633:toxicity; D005240:Feasibility Studies; D005965:Glucuronates / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry; D007275:Injections, Intravenous; D008297:Male; D008422:Materials Testing; D009079:Mucociliary Clearance; D010316:Particle Size; D010539:Permeability; D011142:Polyvinyl Alcohol / Q000737:chemistry; D011205:Povidone / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D020545:Respiratory Mucosa / Q000378:metabolism; D013499:Surface Properties
D000336:Aerosols; D004365:Drugs, Chinese Herbal; D005079:Excipients; D005965:Glucuronates; C484876:scutellarin; D047310:Apigenin; D011142:Polyvinyl Alcohol; D006820:Hyaluronic Acid; D011205:Povidone