Amino-decorated mesoporous silica nanoparticles for controlled sofosbuvir delivery

Area of Science:

• Nanotechnology
• Materials Science
• Pharmaceutical Sciences

Background:

• Sofosbuvir, a Hepatitis C virus medication, is a Biopharmaceutics Classification System (BCS) Class III drug with low bioavailability.
• Mesoporous silica nanoparticles (MSNs) offer potential for controlled drug delivery systems.
• Surface functionalization of MSNs can modulate drug release kinetics and bioavailability.

Purpose of the Study:

• To synthesize and characterize amino-decorated MSNs for sustained delivery of sofosbuvir.
• To evaluate the pharmacokinetic and toxicological profile of sofosbuvir-loaded amino-decorated MSNs.
• To compare the drug release behavior of amino-decorated MSNs with non-functionalized and polyvinyl alcohol (PVA) grafted MSNs.

Main Methods:

• MSNs synthesized via a modified sol-gel method with subsequent amino functionalization.
• Drug loading efficiency determined, and nanoparticle characteristics (size, surface area, pore volume) analyzed.
• In vitro drug release studies conducted, alongside in vivo pharmacokinetic and toxicological evaluations in Sprague-Dawley rats.

Main Results:

• Optimized amino-decorated MSNs (196 nm) entrapped 29.13% sofosbuvir, showing reduced surface area and pore volume.
• Amino-decorated MSNs demonstrated improved thermal stability and Fickian diffusion-controlled sofosbuvir release.
• Toxicological studies confirmed the safety of amino-decorated MSNs, with in vivo studies showing a 2-fold increase in bioavailability and a 3-fold delay in Tmax.

Conclusions:

• Amino-decorated MSNs are a safe and effective platform for sustained sofosbuvir delivery.
• This nanotechnology approach significantly enhances sofosbuvir bioavailability and prolongs its release profile.
• The findings suggest potential for improved Hepatitis C treatment regimens using functionalized MSNs.