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

Abstract

Age-appropriate drug formulations, especially for children, are often limited. A beta-blocker, Carvedilol (CRV) has recently been reported as an off-label option for the management of cardiovascular disorders in pediatric patients. CRV exhibits a pH-dependent solubility and undergoes extensive hepatic metabolism, resulting in low oral bioavailability. Mesoporous silica nanoparticles (MSNs) of two types (MCM-41 and SBA-15) were loaded with CRV at three saturation levels to improve its dissolution rate. At high saturation level, CRV-loaded SBA-15 showed superior dissolution with a dissolution efficiency of 72.42 % and significant dissimilarity (f₁ = 211.80, f₂ = 16.89) compared to pure CRV, demonstrating enhanced solubility and dissolution rate due to its amorphous transformation and large pore diameter. Thermal and diffractometry analysis revealed the adsorption of CRV to MSNs in an amorphous state. CRV-loaded SBA-15 was incorporated into gel bases, and the amount of CRV released from triple-layer loaded gels was found to be higher than monolayer-loaded formulations. The ex vivo skin permeation study revealed a significant enhancement of drug release and permeation for CRV-loaded SBA-15 gel formulations (714.49 ± 38.49 µg/cm²) after 24 h, compared to the control (236.19 ± 18.93 µg/cm²), with flux increased by 62 %. Improving pediatric compliance by providing a convenient, non-invasive, and palatable drug delivery option that minimizes dosing errors and enhances treatment adherence. Our study suggests CRV-loaded SBA-15 transdermal gel as a pediatric-friendly alternative to oral delivery, addressing bitter taste, bypassing hepatic metabolism, and improving bioavailability while reducing side effects.