Francesca Sacchetti1, Domenico D'Arca2, Filippo Genovese3, Salvatore Pacifico4, Eleonora Maretti1, Miriam Hanuskova5, Valentina Iannuccelli1, Maria Paola Costi1, Eliana Leo1. 1. a Department of Life Sciences , University of Modena and Reggio Emilia , Modena , Italy. 2. b Department of Biomedical , Metabolical and Neural Sciences, University of Modena and Reggio Emilia , Modena , Italy. 3. c Centro Interdipartimentale Grandi Strumenti (CIGS) , University of Modena and Reggio Emilia , Modena , Italy. 4. d Department of Pharmaceutical Sciences , University of Ferrara , Ferrara , 44100 , Italy. 5. e Department of Engineering Enzo Ferrari , University of Modena and Reggio Emilia , Modena , Italy.
Abstract
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.
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 humanthymidylate 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.
Entities:
Keywords:
Hydrophilic peptide; cancer cells; endosomal escape; human thymidylate synthase; pH sensitive liposomes