title: Hyaluronic acid-coated liposomes for targeted delivery of paclitaxel, in-vitro characterization and in-vivo evaluation.
abstract: Breast cancer is the leading cause of cancer death in women. Chemotherapy is regarded as the most essential strategy in inhibiting the proliferation of tumor cells. Paclitaxel is a widely used taxane; however, the side effects of available Cremophor-based formulations and also the limitations of passive targeting uncovered an essential need to develop tumor-specific targeted nanocarriers. A hyaluronic acid targeted liposomal formulation of paclitaxel was prepared in which, hyaluronic acid was electrostatistically attracted to the surface of liposomes. Liposomes, had a particle size of 106.4±3.2nm, a weakly negative zeta potential of -9.7±0.8mV and an acceptable encapsulation efficiency of 92.1±1.7%. The release profile of liposomes in buffer showed that 95% of PTX was released during 40h. Confocal laser scanning microscopy and flow cytometry analysis showed the greater cellular internalization of coumarin-loaded liposomes compared to free coumarin. MTT assay on 4T1 and T47D cells demonstrated the stronger cytotoxic activity of liposomes in comparison to free paclitaxel. Cell cycle analysis showed that cells were mainly blocked at G2/M phases after 48h treatment with liposomes. In vivo real time imaging on 4T1 tumor-bearing mice revealed that the liposomal formulation mainly accumulated in the tumor area. Liposomes also had better antitumor efficacy against Cremophor-based formulation. In conclusion, hyaluronic acid targeted paclitaxel liposome can serve as a promising targeted formulation of paclitaxel for future cancer chemotherapy.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 14399-56131, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Ravar
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 14399-56131, Iran.
authors.forename: Ebrahim
authors.initials: E
authors.lastname: Saadat
authors.affiliation: Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Gholami
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 14399-56131, Iran; Medical Biomaterials Research Center, Tehran University of Medical Sciences, Tehran 14399-56131, Iran.
authors.forename: Pouya
authors.initials: P
authors.lastname: Dehghankelishadi
authors.affiliation: Department of Immunology, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Mahdavi
authors.affiliation: Department of Chemistry, Faculty of Science, Karaj Branch, Islamic Azad University, Karaj, Iran.
authors.forename: Samira
authors.initials: S
authors.lastname: Azami
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 14399-56131, Iran; Medical Biomaterials Research Center, Tehran University of Medical Sciences, Tehran 14399-56131, Iran. Electronic address: Dorkoosh@tums.ac.ir.
authors.forename: Farid A
authors.initials: FA
authors.lastname: Dorkoosh
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D008081:Liposomes; D008807:Mice, Inbred BALB C; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008081:Liposomes; D006820:Hyaluronic Acid; D017239:Paclitaxel
keywords: Breast cancer; Hyaluronic acid; Liposome; Paclitaxel; Targeted drug delivery