pH-Sensitive drug delivery system based on modified dextrin coated mesoporous silica nanoparticles

Area of Science:

• Biomaterials Science
• Nanotechnology
• Drug Delivery Systems

Background:

• Developing targeted and stimuli-responsive drug delivery systems is crucial for improving therapeutic efficacy and reducing side effects.
• Mesoporous silica nanoparticles (MSNs) offer a versatile platform for drug encapsulation due to their high surface area and tunable pore size.
• Dextran-based modifications can impart pH-sensitivity to nanomaterials for controlled drug release.

Purpose of the Study:

• To develop and characterize a novel pH-sensitive drug delivery system based on modified dextrin-coated MSNs for doxorubicin hydrochloride (DOX).
• To evaluate the in vitro pH-responsive drug release, cytotoxicity, and cellular uptake of the developed system.
• To assess the in vivo pharmacokinetics, tissue distribution, and tumor accumulation of the DOX-loaded MSNs in a mouse model.

Main Methods:

• Synthesis of dextrin-modified MSNs (MSN-DDA-CL) via oxidation and Schiff's base cross-linking with tetraethylenepentamine.
• Loading of doxorubicin hydrochloride (DOX) into the modified MSNs.
• In vitro drug release studies at different pH values (physiological and weakly acidic).
• Cytotoxicity assays and cell internalization studies using relevant cell lines.
• In vivo pharmacokinetic and biodistribution studies in H22-bearing mice.

Main Results:

• The DOX@MSN-DDA-CL system demonstrated pH-sensitive release of DOX, with minimal release at physiological pH and significant release at pH 6.0.
• In vitro studies confirmed effective cytotoxicity and cellular uptake of the drug-loaded nanoparticles.
• In vivo studies showed prolonged drug retention and enhanced accumulation in tumor tissues compared to free DOX, attributed to EPR and endothelial cell leakiness effects.

Conclusions:

• The pH-sensitive modified dextrin/MSNs complex drug delivery system (DOX@MSN-DDA-CL) effectively controls drug release in response to pH changes.
• The developed nanocarrier exhibits promising characteristics for targeted cancer therapy, including improved tumor accumulation and extended drug retention.
• This novel system holds significant potential for advancing cancer treatment strategies through enhanced drug delivery.