Chitosan nanoparticles to enhance the effect of anticancer drugs

Cancer is difficult to treat due to its early immune invasion and metastasis. In the study presented here, the frequently used chemotherapeutic drugs 5-flourouracil and cisplatin are encapsulated in TPP cross-linked chitosan nanoparticles and their in vitro anti-cancer effect is investigated.

 

 

Chitosan nanoparticles promote the in vitro release, antibacterial and anticancer effects of 5-flourouracil and cisplatin

Ahmad, N.; Khan, M.R.; Palanisamy, S.; Mohandoss, S. Anticancer Drug-Loaded Chitosan Nanoparticles for In Vitro Release, Promoting Antibacterial and Anticancer Activities. Polymers 2023, 15, 3925. https://doi.org/10.3390/polym15193925

Cancer is considered one of the deadliest diseases in the world and is one of the main causes of morbidity. For efficient treatment, early immune invasion and metastasis of cancer cells are the main problems. Disease is treated by surgery, radiation and chemotherapy. In chemotherapy, agents such as 5-flourouracil (FA), cisplatin (CP), gemcitabine, and doxorubicin are commonly used.

Their therapeutic benefit can be improved by the use of nanoparticles. In addition to an increased effect, the dose and thus the side effects that occur can be reduced. Chitosan nanoparticles (CTS-NPs) are promising for this purpose, especially due to the good biodegradability, biocompatibility and non-toxic properties of CTS. Typical production methods for nanoparticles are: spray drying, ionotropic gelation, chemical crosslinking, and precipitation. Of these, ionotropic gelation is particularly popular. There, chitosan and a crosslinker such as TPP are mixed under stirring and the nanoparticles are formed due to the electrostatic interaction between the positively-charged CTS and the negatively-charged TPP. TPP is often used as a crosslinker for CTS because it is non-toxic, leads to rapid gelation, and when combined with CTS as CTS-TPP-NPs, leads to prolonged release time and higher efficiency of drugs.

For this reason, in the presented study, FA and CP are encapsulated in CTS NPs cross-linked with TPP. Therefore, a chitosan with a molecular weight of 50-190 kDa was used. The NPs are prepared via ionotropic gelation in this process. The particle size, shape and structure of the NPs, as well as the drug release of FA and CP are characterized. In addition, the physiochemical properties of FA-CTS-TPP-NPs, CP-CTS-TPP-NPs and CTS-TPP-NPs, antimicrobial activity against St. aureus and E. coli, in vitro anti-cancer effect and cytotoxicity will be investigated.

RESULTS

• Good dispersion of the nanoparticles with diameters of 395.3±14.3 nm (CTS-TPP-NPs), 126.7±2.6 nm (CP-CTS-TPP-NPs) and 82.5±2.3 nm (FA-CTS-TPP-NPs)
• In vitro release studies showed controlled and sustained release of CP and FA from the CTS-TPP NPs, with release amounts of 72.9±3.6% and 94.8±2.9%, respectively
• Better antimicrobial activity of FA-CTS-TPP NPs (91.37±4.37% and 89.28±3.19%) compared with CP-CTS-TPP NPs (63.41±3.84% and 57.62±4.28%) against E. coli and St. aureus, respectively
• In the cytotoxicity and live/dead assay experiments, it was shown that the anticancer activity of FA-CTS-TPP-NPs and CP-CTS-TPP-NPs was higher than that of CTS-TPP-NPs and CP/FA drugs

Conclusion: TPP crosslinked CTS-NPs loaded with CP and FA have great potential for future uses in clinical and biomedical applications.

Link to article: https://www.mdpi.com/2073-4360/15/19/3925

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