Cross-Linked Thiolated Hydroxypropil-β-Cyclodextrin for Pulmonary Drug Delivery

Area of Science:

• Pharmaceutical Sciences
• Biomaterials Science
• Drug Delivery

Background:

• Inhalable cyclodextrins (CDs) enhance solubility and absorption for pulmonary drug delivery.
• Thiolated hydroxypropyl-β-cyclodextrin (HP-β-CD-SH) exhibits mucoadhesion and self-aggregation, improving drug absorption, stability, and reducing irritation.
• Stabilizing CD nanoaggregates is crucial for optimizing lung drug delivery systems.

Purpose of the Study:

• To stabilize CD nanoaggregates using bifunctional cross-linkers.
• To evaluate the benefits of stabilized nanoaggregates for lung drug delivery compared to pristine HP-β-CD-SH.
• To assess the efficacy of these systems with dexamethasone (DMS) and olive leaf extracts (OLE).

Main Methods:

• Synthesis of HP-β-CD-SH via microwave reaction with 25% thiolation.
• Preparation and characterization of HP-β-CD-SH nanoaggregates and stabilized nanoparticles (HP-β-CD-SH-NP).
• Evaluation of drug permeation and activity using a lung epithelial Air-Liquid Interface (ALI) model with DMS and OLE.

Main Results:

• HP-β-CD-SH formed 150 nm nanoaggregates and stabilized 400 nm HP-β-CD-SH-NP.
• All carriers demonstrated good complexing ability with DMS and OLE and were biocompatible in the ALI model.
• HP-β-CD-SH enhanced DMS absorption, while stabilized HP-β-CD-SH-NP provided protection against oxidative stress.

Conclusions:

• HP-β-CD-SH shows significant promise for pulmonary drug delivery.
• Stabilized HP-β-CD-SH nanoaggregates offer enhanced drug absorption and stability.
• This formulation provides a versatile platform for administering labile molecules, including natural extracts, via inhalation.