Chitosan-Coated Cinnamon/Oregano-Loaded Solid Lipid Nanoparticles to Augment 5-Fluorouracil Cytotoxicity for Colorectal Cancer: Extract Standardization, Nanoparticle Optimization, and Cytotoxicity Evaluation

Abstract

This study aimed to coat lipid-based nanocarriers with chitosan to encapsulate nutraceuticals, minimize opsonization, and facilitate passive-targeting. Phase one was concerned with standardization according to the World Health Organization. Qualitative analysis using liquid chromatography-high-resolution mass spectrometry (LC-HRMS/MS) investigated the active constituents, especially reported cytotoxic agents. Cinnamaldehyde and rosmarinic acid were selected to be quantified using high-performance liquid chromatography. Phase two was aimed to encapsulate both extracts in solid lipid nanoparticles (core) and chitosan (shell) to gain the advantages of both materials properties. The developed experimental model suggested an optimum formulation with 2% lipid, 2.3% surfactant, and 0.4% chitosan to achieve a particle size of 254.77 nm, polydispersity index of 0.28, zeta potential of +15.26, and entrapment efficiency percentage of 77.3% and 69.1% for cinnamon and oregano, respectively. Phase three was focused on the evaluation of cytotoxic activity unencapsulated/encapsulated cinnamon and oregano extracts with/without 5-fluorouracil on HCT-116 cells. This study confirmed the success of the suggested combination with 5-fluorouracil for treating human colon carcinoma with a low dose leading to decreasing side effects and allowing uninterrupted therapy.

Chemical profiling and pharmaco‐toxicological activity ofOriganum sipyleumextracts: Exploring for novel sources for potential therapeutic agents

“…On the contrary, EA extract reduced significantly cell viability (<60% compared to control group; Figure 6). This result is consistent with the findings by Kamel, Khalil, Rateb, Elgendy, and Elhawary (2017), who observed a reduction of HCT116 cell viability after challenging the cells with an ethanol Origanum extract, that exerted antiproliferative effects at concentrations < 100 µg/ml. Conversely, all extracts did not modify spontaneous cell migration, in wound healing test, thus excluding any effect on migration and invasion capacities of HCT116 human colon cancer cells (Figure 7).…”

A Review of Biodegradable Natural Polymer-Based Nanoparticles for Drug Delivery Applications

“…Zhang et al modified chitosan by using heptamethine and folate for photodynamic treatment and tumor-imaging [ 54 ]. Kamel et al modified chitosan by encapsulating oregano and cinnamon within chitosan in combination with 5-fluorouracil as an effective agent for tumors [ 55 ]. Lin et al studied chitosan derivatives and found that chitosan-based nanocarriers used for co-delivery of genes and drugs were redox responsive [ 56 ].…”

Colorectal cancer combination therapy using drug and gene co-delivered, targeted poly(ethylene glycol)-&epsilon;-poly(caprolactone) nanocarriers

“…Kamel et al prepared chitosan-coated cinnamon/oregano-loaded solid lipid nanoparticles to augment 5-FU cytotoxicity for colorectal cancer. 21 Pretel et al utilized nanoprecipitation and solvent evaporation methods to optimize poly( d , l -lactide-co-glycolide) nanoparticles for the delivery of 5-FU. 22 In Sharma et al’s investigation, 5-FU was conjugated to PEG-anchored recombinant human serum albumin nanoparticles to improve the pharmacokinetics and therapeutic profiles.…”