Cyclodextrin nanoparticle bound oral camptothecin for colorectal cancer: Formulation development and optimization

Area of Science:

• Nanotechnology
• Materials Science
• Pharmaceutical Sciences

Background:

• Colorectal cancer (CRC) is a leading global cause of death, with current intravenous chemotherapies facing limitations like poor oral bioavailability and non-specific distribution.
• Parenteral administration of chemotherapy for CRC presents challenges in efficacy due to non-selective biodistribution and administration difficulties.

Purpose of the Study:

• To develop novel cyclodextrin (CD)-based cationic nanoparticles (NPs) for oral administration of camptothecin (CPT) to enhance colorectal cancer treatment.
• To protect CPT within the gastrointestinal tract, promote mucus layer accumulation, and achieve effective local tumor treatment.

Main Methods:

• Preparation of amphiphilic CD-based NPs coated with polyethylenimine (PEI) or chitosan (CS) to achieve a positive surface charge.
• Optimization of NP formulation, resulting in CPT-loaded Poly-β-CD-C6 NPs (135 nm diameter, +40 mV zeta potential).
• In vitro release studies simulating gastrointestinal conditions, cytotoxicity assays on HT-29 cells, and Caco-2 cell permeability studies.

Main Results:

• An optimal formulation of CPT-loaded Poly-β-CD-C6 NPs was identified with a particle size of 135 nm and a zeta potential of +40 mV.
• In vitro studies demonstrated 52% CPT delivery to the simulated colon, indicating successful gastrointestinal transit.
• CPT-loaded NPs showed enhanced cytotoxicity against HT-29 cells and a 276% increase in Caco-2 cell permeability, with significantly improved mucosal penetration.

Conclusions:

• Cationic cyclodextrin nanoparticles offer a promising strategy for oral delivery of colorectal cancer chemotherapy, overcoming limitations of conventional intravenous administration.
• The developed NPs effectively protect the drug, enhance its penetration, and improve its cytotoxic effect on colorectal cancer cells.
• This approach holds potential for more effective and localized treatment of colorectal tumors via oral administration.