Investigations on nanoconfinement of low-molecular antineoplastic agents into biocompatible magnetic matrices for drug targeting
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Alina Maria Tomoiaga1, Bogdan Ionel Cioroiu2, Valentin Nica3
1Department of Chemistry, "Alexandru Ioan Cuza" University of Iasi, 11 Carol I Boulevard, 700506 Iasi, Romania; Research Department, ChemPerformance Ltd., 37 Fintinilor Street, 700337 Iasi, Romania.
Abstract:
Magnetic mesoporous silica nanoparticles are employed as biocompatible matrices to host low-molecular antineoplastic drugs. 5-Fluorouracil is a well-known antimetabolite drug used to treat many malignancies: colon, rectal, breast, head and neck, pancreatic, gastric, esophageal, liver and G-U (bladder, penile, vulva, prostate), skin cancers (basal cell and keratosis). Unfortunately severe gastrointestinal, hematological, neural, cardiac and dermatological toxic effects are often registered due to its cytotoxicity. Thus, this work focuses on development of a magnetic silica nanosystem, capable of hosting high amounts of 5-fluorouracil and delivers it in a targeted manner, under the influence of external magnetic field. There are few reports on nanoconfinement of this particular small molecule antimetabolite on mesoporous silica hosts. Therefore we have investigated different ways to confine high amounts of 5-FU within amino-modified and non-modified mesopores of the silica shell, from water and ethanol, under magnetic stirring and ultrasound irradiation. Also, we have studied the adsorption process from water as a function of pH in order to rationalize drug-support interactions. It is shown that nature of the solvent has great influence on diffusion of small molecules into mesopores, which is slower from alcoholic solutions. More importantly, sonication is proven as an excellent alternative to long adsorption tests, since the time necessary to reach equilibrium is drastically reduced to 1h and higher amounts of drug may be immobilized within the mesopores of amino-modified magnetic silica nanoparticles. These results are highly important for optimization of drug immobilization process in order to attain desired release profile.
Insights
Magnetic silica nanoparticles effectively host high amounts of 5-fluorouracil (5-FU), a cancer drug. Ultrasound irradiation significantly speeds up drug loading and enhances immobilization on these nanocarriers for targeted delivery.
Area of Science:
- Nanotechnology
- Materials Science
- Oncology
Background:
- 5-Fluorouracil (5-FU) is a widely used antineoplastic drug with significant cytotoxic side effects.
- Developing targeted drug delivery systems is crucial to mitigate 5-FU toxicity and improve efficacy.
- Mesoporous silica nanoparticles offer a promising biocompatible matrix for drug encapsulation.
Purpose of the Study:
- To develop a magnetic silica nanosystem for enhanced loading and targeted delivery of 5-fluorouracil (5-FU).
- To investigate methods for high-volume confinement of 5-FU within mesoporous silica nanoparticles.
- To optimize the drug immobilization process for controlled release applications.
Main Methods:
- Synthesis of magnetic mesoporous silica nanoparticles.
- Investigation of 5-FU adsorption into modified and non-modified silica mesopores using water and ethanol solvents.
- Evaluation of adsorption kinetics under magnetic stirring and ultrasound irradiation.
- Study of pH-dependent adsorption from aqueous solutions.
Main Results:
- Solvent choice significantly impacts 5-FU diffusion into mesopores, with slower diffusion observed from alcoholic solutions.
- Ultrasound irradiation drastically reduces adsorption equilibrium time to 1 hour, enabling efficient drug loading.
- Amino-modified magnetic silica nanoparticles demonstrated higher drug immobilization capacity.
- pH influences drug-support interactions, crucial for rationalizing the adsorption process.
Conclusions:
- Magnetic mesoporous silica nanoparticles are effective carriers for high-capacity 5-FU loading.
- Ultrasound-assisted adsorption is a rapid and efficient method for immobilizing 5-FU.
- Optimized immobilization on magnetic silica nanocarriers facilitates targeted drug delivery and controlled release, potentially reducing systemic toxicity.
