Folate-Modified Chitosan 5-Flourouraci Nanoparticles-Embedded Calcium Alginate Beads for Colon Targeted Delivery

Area of Science:

• Biomaterials Science
• Nanotechnology
• Drug Delivery Systems
• Colorectal Cancer Therapeutics

Background:

• Alginate acid forms stable gel beads with divalent cations, exhibiting pH-responsive swelling and dissolution properties.
• Folate-modified chitosan nanoparticles encapsulating 5-fluorouracil (FA-CS-5FU-NPs) are designed for targeted delivery.
• Colon-specific drug delivery is crucial for treating colorectal conditions, minimizing systemic toxicity.

Purpose of the Study:

• To embed folate-modified chitosan 5FU nanoparticles (FA-CS-5FU-NPs) into calcium alginate beads for enhanced colon targeting.
• To compare the characteristics and performance of freeze-dried (FA-CS-5FU-NP-Bf) and oven-dried (FA-CS-5FU-NP-Bo) beads.
• To evaluate the in vitro release kinetics, pharmacokinetic profiles, and biodistribution of 5-fluorouracil (5FU) from the developed systems.

Main Methods:

• Calcium alginate beads incorporating FA-CS-5FU-NPs were prepared using freeze-drying and oven-drying methods.
• Characterization included size analysis, swelling index (SI), erosion index (EI), and water-uptake index (WUI) at simulated intestinal pH.
• In vitro 5FU release studies, pharmacokinetic analysis (Cmax, AUC, T1/2, Vd), and biodistribution studies in the colon were conducted.

Main Results:

• FA-CS-5FU-NP-Bf beads were larger with higher SI, EI, and WUI compared to FA-CS-5FU-NP-Bo beads at intestinal pH.
• Both bead types exhibited sustained-release behavior compared to pure 5FU solution, with FA-CS-5FU-NPs showing a faster release rate.
• Biodistribution studies confirmed maximum drug accumulation in the colon for nanoparticles-embedded beads, with FA-CS-5FU-NP-Bo showing specific colon targeting by avoiding early release in the stomach and small intestine.

Conclusions:

• Oven-dried folate-modified chitosan 5FU nanoparticles-embedded calcium alginate beads (FA-CS-5FU-NP-Bo) are effective for colon-targeted delivery of 5-fluorouracil (5FU).
• The FA-CS-5FU-NP-Bo system demonstrates sustained-release properties and preferential drug accumulation in the colon, potentially improving colorectal cancer treatment efficacy.
• This formulation offers a promising strategy for localized chemotherapy in the colon, reducing systemic side effects.