Conveying a newly designed hydrophilic anti-human thymidylate synthase peptide to cisplatin resistant cancer cells: are pH-sensitive liposomes more effective than conventional ones?

Autor: Miriam Hanuskova, Valentina Iannuccelli, Salvatore Pacifico, Francesca Sacchetti, Eliana Grazia Leo, Domenico D'Arca, Filippo Genovese, Maria Paola Costi, Eleonora Maretti
Rok vydání: 2016
Předmět:
0301 basic medicine
Cell Survival
Pharmaceutical Science
Peptide
02 engineering and technology
human thymidylate synthase
endosomal escape
Biology
Thymidylate synthase
NO
03 medical and health sciences
Drug Delivery Systems
Cell Line
Tumor
Drug Discovery
medicine
Humans
pH sensitive liposomes
cancer cells
Hydrophilic peptide
Pharmacology
Cisplatin
chemistry.chemical_classification
hydrophilic peptide
pH sensitive liposomes
cancer cells
human thymidylate synthase
endosomal escape
Liposome
Dose-Response Relationship
Drug
hydrophilic peptide
Organic Chemistry
Cancer
Thymidylate Synthase
Hydrogen-Ion Concentration
021001 nanoscience & nanotechnology
medicine.disease
In vitro
Treatment Outcome
030104 developmental biology
Biochemistry
chemistry
Drug Resistance
Neoplasm
Drug Design
Liposomes
Cancer cell
Drug delivery
biology.protein
0210 nano-technology
Hydrophobic and Hydrophilic Interactions
medicine.drug
Zdroj: Drug Development and Industrial Pharmacy. 43:465-473
ISSN: 1520-5762
0363-9045
Popis: Context: LR-peptide, a novel hydrophilic peptide synthetized and characterized in previous work, is able to reduce the multi-drug resistance response in cisplatin (cDPP) resistant cancer cells by inhibiting human thymidylate synthase (hTS) overexpressed in several tumors, including ovarian and colon-rectal cancers, but it is unable to enter the cells spontaneously. Objective: The aim of this work was to design and characterize liposomal vesicles as drug delivery systems for the LR peptide, evaluating the possible benefits of the pH-responsive feature in improving intracellular delivery. Materials and methods: For this purpose, conventional and pH-sensitive liposomes were formulated, compared regarding their physical-chemical properties (size, PDI, morphology, in vitro stability and drug release) and studied for in vitro cytotoxicity against a cDDP-resistant cancer cells. Results and discussion: Results indicated that LR peptide was successfully encapsulated in both liposomal formulations but at short incubation time only LR loaded pH-sensitive liposomes showed cell inhibition activity while for long incubation time the two kinds of liposomes demonstrated the same efficacy. Conclusions: Data provide evidence that acidic pH-triggered liposomal delivery is able to significantly reduce the time required by the systems to deliver the drug to the cells without inducing an enhancement of the efficacy of the drug.
Databáze: OpenAIRE
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