Development of chitosan-SLN microparticles for chemotherapy: in vitro approach through efflux-transporter modulation

Area of Science:

• Nanotechnology
• Pharmacology
• Oncology

Background:

• Drug efflux-transporters limit anticancer drug efficacy by reducing concentrations at target sites.
• Modulating efflux-transporter activity is a key strategy to improve cancer therapy.
• Phenethyl Isothiocyanate (PEITC) is a tumor-suppressive agent susceptible to efflux transporters.

Purpose of the Study:

• To develop and evaluate a novel particle drug delivery system for pulmonary delivery of PEITC.
• To investigate the use of Solid Lipid Nanoparticle (SLN) and chitosan-based microparticles (CSM) for co-delivery of efflux-transporter inhibitors and PEITC.
• To assess the impact of efflux-transporter inhibition on PEITC release, cellular uptake, and cytotoxicity.

Main Methods:

• Development of Chitosan-SLN Microparticles (CSM) encapsulating PEITC and efflux-transporter inhibitors (tamoxifen, verapamil HCl, nifedipine).
• In vitro evaluation of drug release profiles for both inhibitors and PEITC from CSM.
• Assessment of PEITC cytotoxicity in Calu-3 cells in the presence and absence of efflux-transporter inhibitors.

Main Results:

• CSM demonstrated an initial burst release of efflux-transporter inhibitors followed by sustained release of PEITC.
• The presence of inhibitors significantly enhanced PEITC uptake by Calu-3 cells.
• A subsequent increase in PEITC cytotoxicity was observed when efflux transporters were inhibited.

Conclusions:

• Chitosan-SLN Microparticles (CSM) are an effective drug delivery system for overcoming efflux-transporter-mediated drug resistance.
• This co-delivery strategy enhances the pulmonary delivery and therapeutic efficacy of PEITC.
• CSM holds promise for improving cancer treatment by increasing drug concentration at the tumor site.