Mesoporous silica nanoparticles-embedded hydrogel: A potential approach for transdermal delivery of carvedilol to...

Area of Science:

• Pharmaceutical Sciences
• Nanotechnology
• Pediatric Medicine

Background:

• Limited age-appropriate drug formulations pose challenges in pediatric care.
• Carvedilol (CRV), a beta-blocker, is used off-label for pediatric cardiovascular disorders but has low oral bioavailability due to pH-dependent solubility and extensive hepatic metabolism.
• Developing effective and compliant pediatric drug delivery systems is crucial.

Purpose of the Study:

• To enhance the dissolution rate and oral bioavailability of Carvedilol (CRV) using mesoporous silica nanoparticles (MSNs).
• To develop and evaluate a transdermal gel formulation of CRV-loaded MSNs for pediatric application.
• To assess the ex vivo skin permeation and potential of the transdermal gel as a pediatric-friendly drug delivery system.

Main Methods:

• Carvedilol (CRV) was loaded into two types of mesoporous silica nanoparticles (MSNs): MCM-41 and SBA-15, at varying saturation levels.
• CRV-loaded MSNs were characterized for drug loading, dissolution, and physical state (amorphous transformation confirmed by thermal and diffractometry analysis).
• CRV-loaded SBA-15 was incorporated into triple-layer gel formulations, and ex vivo skin permeation studies were conducted.

Main Results:

• CRV-loaded SBA-15 at high saturation demonstrated superior dissolution efficiency (72.42%) and significant dissimilarity to pure CRV, indicating enhanced solubility and dissolution rate.
• Thermal and diffractometry analyses confirmed CRV adsorption to MSNs in an amorphous state, contributing to improved dissolution.
• Ex vivo studies showed significantly enhanced CRV permeation from SBA-15 gel formulations (714.49 ± 38.49 µg/cm²) compared to controls (236.19 ± 18.93 µg/cm²), with a 62% increase in flux.

Conclusions:

• CRV-loaded SBA-15 nanoparticles effectively improve Carvedilol's dissolution rate and solubility.
• The developed transdermal gel formulation offers enhanced skin permeation, representing a viable non-invasive delivery route.
• This pediatric-friendly transdermal gel addresses challenges of oral CRV delivery, including bitter taste and hepatic metabolism, potentially improving compliance and bioavailability.