Chitosomes Loaded with Docetaxel as a Promising Drug Delivery System to Laryngeal Cancer Cells: An In Vitro Cytotoxic Study

Abstract

Current delivery of chemotherapy, either intra-venous or intra-arterial, remains suboptimal for patients with head and neck tumors. The free form of chemotherapy drugs, such as docetaxel, has non-specific tissue targeting and poor solubility in blood that deters treatment efficacy. Upon reaching the tumors, these drugs can also be easily washed away by the interstitial fluids. Liposomes have been used as nanocarriers to enhance docetaxel bioavailability. However, they are affected by potential interstitial dislodging due to insufficient intratumoral permeability and retention capabilities. Here, we developed and characterized docetaxel-loaded anionic nanoliposomes coated with a layer of mucoadhesive chitosan (chitosomes) for the application of chemotherapy drug delivery. The anionic liposomes were 99.4 ± 1.5 nm in diameter with a zeta potential of −26 ± 2.0 mV. The chitosan coating increased the liposome size to 120 ± 2.2 nm and the surface charge to 24.8 ± 2.6 mV. Chitosome formation was confirmed via FTIR spectroscopy and mucoadhesive analysis with anionic mucin dispersions. Blank liposomes and chitosomes showed no cytotoxic effect on human laryngeal stromal and cancer cells. Chitosomes were also internalized into the cytoplasm of human laryngeal cancer cells, indicating effective nanocarrier delivery. A higher cytotoxicity (p < 0.05) of docetaxel-loaded chitosomes towards human laryngeal cancer cells was observed compared to human stromal cells and control treatments. No hemolytic effect was observed on human red blood cells after a 3 h exposure, proving the proposed intra-arterial administration. Our in vitro results supported the potential of docetaxel-loaded chitosomes for locoregional chemotherapy delivery to laryngeal cancer cells.

Formulation of silymarin surface modified vesicles: In vitro characterization to cell viability assessment

“…It is a biocompatible delivery system and can encapsulate both the water soluble and insoluble drugs. It can modulate the drug release and protect the drug from the rapid degradation ( Melchior et al, 2023 , Moya-Garcia et al, 2023 ). The beneficial effects of natural bioactive compound may be limited by their poor bioavailability and stability ( Asmaa et al, 2023 , De Luca et al, 2022 ) .…”

“…Bioadhesive polymers can also be used to modify the surface of vesicles in order to enhance the drug entrapment, physical and colloidal stability, and bioavailability ( Sun et al, 2020 , Megahed et al, 2022 , Zhang et al, 2019 ) . Since non-adhesive nano-carrier uptake is hampered by high interstitial intratumoral pressures ( Moya-Garcia et al, 2023 ). So, chitosan (CHT) can be used as a mucoadhesive agent by altering the anionic vesicles' surface.…”

“…It binds to the anionic glycoproteins in mucin by electrostatic interactions ( Collado-González et al, 2019 ). Additionally, it has been demonstrated that chitosan-coated nanocarriers enhances transcellular and paracellular drug transport and have a decreased aggregation in the liver and blood ( Moya-Garcia et al, 2023 , Megahed et al, 2022 , Pandey et al, 2022 ) . There are numerous chitosan coated drug delivery systems developed and reported for their biological activities ( Hilitanu et al, 2024 , Sharifi-Rad et al, 2021 , Confederat et al, 2021 ) .…”

Special Issue “Application Progress of Liposomes in Drug Development”

“…This selective targeting improves the therapeutic index and reduces off-target effects. These features are highlighted in the papers published by Moya-Garcia et al, Poudel et al, and Alrbyawi et al [ 6 , 7 , 8 ].…”

“…Moya-Garcia et al [ 6 ] explore the development and characterization of chitosan-coated liposomes (chitosomes) as a drug delivery system for docetaxel targeting laryngeal squamous cell carcinoma (LSCC). Their study is focused on evaluating the physical properties of the nanocarriers, including size, charge, stability, and mucoadhesiveness, as well as assessing their cytotoxic effects on cancer cells and healthy stromal cells.…”