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Rapid and improved oral absorption of N-butylphthalide by sodium cholate-appended liposomes for efficient ischemic stroke therapy
- Source :
- Drug Delivery, Vol 28, Iss 1, Pp 2469-2479 (2021), Drug Delivery, article-version (VoR) Version of Record
- Publication Year :
- 2021
- Publisher :
- Informa UK Limited, 2021.
-
Abstract
- As a multi-target drug to treat ischemic stroke, N-butylphthalide (NBP) is extremely water-insoluble and exhibits limited oral bioavailability, impeding its wide oral application. Effective treatment of ischemic stroke by NBP requires timely and efficient drug exposure, necessitating the development of new oral formulations. Herein, liposomes containing biosurfactant sodium cholate (CA-liposomes) were systemically investigated as an oral NBP delivery platform because of its high biocompatibility and great potential for clinical applications. The optimized liposomes have a uniform hydrodynamic size of 104.30 �� 1.60 nm and excellent encapsulation efficiency (93.91 �� 1.10%). Intriguingly, NBP-loaded CA-liposomes produced rapid drug release and the cumulative release was up to 88.09 �� 4.04% during 12 h while that for NBP group was only 6.79 �� 0.99%. Caco-2 cell monolayer assay demonstrated the superior cell uptake and transport efficiency of NBP-loaded CA-liposomes than free NBP, which was mediated by passive diffusion via transcellular and paracellular routes. After oral administration to rats, NBP-loaded CA-liposomes exhibited rapid and almost complete drug absorption, with a tmax of 0.70 �� 0.14 h and an absolute bioavailability of 92.65% while NBP suspension demonstrated relatively low bioavailability (21.7%). Meanwhile, NBP-loaded CA-liposomes produced 18.30-fold drug concentration in the brain at 5 min compared with NBP suspension, and the brain bioavailability increased by 2.48-fold. As expected, NBP-loaded CA-liposomes demonstrated significant therapeutic efficacy in a middle cerebral artery occlusion rat model. Our study provides new insights for engineering oral formulations of NBP with fast and sufficient drug exposure against ischemic stroke in the clinic.
- Subjects :
- Male
Drug
Biocompatibility
Chemistry, Pharmaceutical
media_common.quotation_subject
Pharmaceutical Science
RM1-950
Pharmacology
Rats, Sprague-Dawley
Random Allocation
Oral administration
ischemic stroke
n-butylphthalide
Animals
Humans
Tissue Distribution
Particle Size
Sodium Cholate
Transcellular
drug release
Benzofurans
media_common
Drug Carriers
Liposome
Dose-Response Relationship, Drug
Chemistry
rapid absorption
General Medicine
Rats
Bioavailability
Disease Models, Animal
Drug Liberation
brain accumulation
Neuroprotective Agents
Area Under Curve
Paracellular transport
Liposomes
Therapeutics. Pharmacology
Caco-2 Cells
Research Article
Subjects
Details
- ISSN :
- 15210464 and 10717544
- Volume :
- 28
- Database :
- OpenAIRE
- Journal :
- Drug Delivery
- Accession number :
- edsair.doi.dedup.....3d43638c3e249b586ff997aeac94f67f