Engineered Microencapsulated Lactoferrin Nanoconjugates for Oral Targeted Treatment of Colon Cancer

Area of Science:

• Biomaterials Science
• Nanotechnology
• Drug Delivery Systems

Background:

• Colorectal cancer (CRC) lacks convenient oral therapeutics despite targeted therapy advancements.
• Lactoferrin nanoparticles (Lf NPs) show promise for cancer therapy but face oral delivery challenges.
• Microencapsulation can overcome Lf NP oral delivery barriers, protecting cargo and controlling release.

Purpose of the Study:

• To develop nanoparticle-in-microparticle delivery systems (NIMDs) for oral delivery of docetaxel (DTX) and atorvastatin (ATR).
• To evaluate the stability and release profile of NIMDs in the gastrointestinal tract.
• To assess the efficacy of NIMDs in a colorectal cancer model.

Main Methods:

• Dual conjugation of DTX and ATR into lactoferrin (Lf) backbone to form NPs.
• Microencapsulation of Lf NPs into calcium-crosslinked microparticles using hybrid copolymers.
• In vitro gastrointestinal tract stability testing and in vivo rat cecal content release studies.
• In vivo efficacy study in colorectal cancer model assessing key signaling pathways.

Main Results:

• NIMDs exhibited no detectable drug release in the upper gastrointestinal tract, unlike free NPs.
• Sustained release of Lf NPs from NIMDs was observed in rat cecal content.
• In vivo studies showed NIMDs significantly suppressed p-AKT, p-ERK1/2, and NF-κB, outperforming free NPs in CRC treatment.

Conclusions:

• NIMDs offer a viable strategy for oral delivery of protein-based nanoparticles.
• Microencapsulation protects therapeutic payloads and enables targeted delivery to the colon.
• This approach enhances the therapeutic efficacy of NPs for colorectal cancer treatment.