Cross-Linked Thiolated Hydroxypropil-ß-Cyclodextrin for Pulmonary Drug Delivery.
Int J Mol Sci
; 25(17)2024 Aug 29.
Article
in En
| MEDLINE
| ID: mdl-39273341
ABSTRACT
Inhalable formulations with cyclodextrins (CDs) as solubility and absorption enhancers show promise for pulmonary delivery. Thiolated hydroxypropyl-ß-cyclodextrin (HP-ß-CD-SH) has mucoadhesive properties, enhancing drug absorption. Moreover, it has self-aggregation capability, which could further improve absorption and drug stability, as well as reduce irritation. This study aims to stabilize CD nanoaggregates using bifunctional cross-linkers and evaluate their benefits for lung drug delivery compared to pristine HP-ß-CD-SH. METHODS:
The effectiveness of cross-linked HP-ß-CD-SH nanoparticles (HP-ß-CD-SH-NP) was compared to transient nanoaggregates in enhancing the activity of dexamethasone (DMS) and olive leaf extracts (OLE). DMS, a poorly soluble drug commonly used in lung treatments, and OLE, known for its antioxidant properties, were chosen. Drug-loaded HP-ß-CD-SH-NP were prepared and nebulized onto a lung epithelial Air-Liquid Interface (ALI) model, assessing drug permeation and activity.RESULTS:
HP-ß-CD-SH with 25% thiolation was synthesized via microwave reaction, forming 150 nm nanoaggregates and stabilized 400 nm HP-ß-CD-SH-NP. All carriers showed good complexing ability with DMS and OLE and were biocompatible in the lung ALI model. HP-ß-CD-SH promoted DMS absorption, while stabilized HP-ß-CD-SH-NP protected against oxidative stress.CONCLUSION:
HP-ß-CD-SH is promising for lung delivery, especially as stabilized nanoaggregates, offering versatile administration for labile molecules like natural extracts.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Dexamethasone
/
Drug Delivery Systems
/
2-Hydroxypropyl-beta-cyclodextrin
Limits:
Animals
/
Humans
Language:
En
Journal:
Int J Mol Sci
Year:
2024
Document type:
Article
Affiliation country:
Italy
Country of publication:
Switzerland