Folate-polyethylene glycol conjugated carboxymethyl chitosan for tumor-targeted delivery of 5-fluorouracil
Hai-Lang Li1, Ya-Xing He1, Qian-Hong Gao1
1Department of Radiation Chemistry and Engineering, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, P.R. China.
Abstract:
Targeted drug delivery has been evolving at an increasing rate due to its potential to reduce the minimum effective dose of a drug and its accompanying side effects. It has shown improved therapeutic efficacy at equivalent plasma concentrations; however, the development of effective targeted delivery systems has remained a major task. In this study, a drug carrier was designed and synthesized by conjugation of folate acid (FA) to carboxymethyl chitosan (CMCS) through a polyethylene glycol (PEG) spacer. The resulting conjugates were confirmed by 1H nuclear magnetic resonance and infrared spectroscopy. The cytotoxicity of CMCS and CMCS‑5‑fluorouracil (5‑FU) was determined by a crystal violet stain assay. The potential of CMCS‑PEG‑FA for use in the targeted delivery of 5‑FU was investigated using 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide analysis in two cell lines, HeLa and A549, which contain different numbers of folate receptors on their surfaces. The MTT results revealed that in HeLa cells, the cytotoxicity of (CMCS‑5‑FU)‑PEG‑FU cells is greater compared with CMCS‑5‑FU, suggesting that folate receptor‑mediated endocytosis may affect the cellular uptake efficiency of 5‑FU‑loaded CMCS‑PEG‑FA. The CMCS‑PEG‑FA conjugates presented in this study show promise as carriers for chemotherapeutic agents due to their solubility at physiological pH, efficiency in carrying chemotherapeutic agents, low cytotoxicity and targeting ability.
Insights
Researchers developed a novel drug carrier by linking folate acid (FA) to carboxymethyl chitosan (CMCS) using a polyethylene glycol (PEG) spacer. This targeted delivery system enhances chemotherapy efficacy and reduces side effects.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Drug Delivery Systems
Background:
- Targeted drug delivery aims to enhance therapeutic efficacy and minimize side effects by reducing the effective drug dose.
- Developing efficient targeted delivery systems remains a significant challenge in pharmaceutical research.
- Carboxymethyl chitosan (CMCS) and folate acid (FA) are biocompatible materials with potential for drug delivery applications.
Purpose of the Study:
- To design and synthesize a novel drug carrier system for targeted delivery of chemotherapeutic agents.
- To investigate the potential of folate acid-conjugated carboxymethyl chitosan (CMCS-PEG-FA) for targeted delivery of 5-fluorouracil (5-FU).
- To evaluate the cellular uptake and cytotoxicity of the developed drug carrier in cancer cell lines.
Main Methods:
- Synthesis of CMCS-PEG-FA conjugates confirmed by 1H NMR and infrared spectroscopy.
- Cytotoxicity assessment using crystal violet stain assay for CMCS and CMCS-5-FU.
- In vitro evaluation of CMCS-PEG-FA targeting ability using MTT assay in HeLa and A549 cell lines.
Main Results:
- The synthesized CMCS-PEG-FA conjugates were confirmed structurally.
- CMCS-PEG-FA demonstrated enhanced cytotoxicity of 5-FU in HeLa cells compared to CMCS-5-FU.
- Results suggest folate receptor-mediated endocytosis enhances cellular uptake of 5-FU-loaded CMCS-PEG-FA.
Conclusions:
- CMCS-PEG-FA conjugates show promise as effective carriers for chemotherapeutic agents.
- The developed system exhibits good solubility at physiological pH and efficiency in drug loading.
- The targeting ability of CMCS-PEG-FA holds potential for improved cancer therapy with reduced side effects.
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