Tat peptide and hexadecylphosphocholine introduction into pegylated liposomal doxorubicin: An in vitro and in vivo study on drug cellular delivery, release, biodistribution and antitumor activity

• Published in: International journal of pharmaceutics 2016-09, Vol.511 (1), p.236-244
• Main Authors: Teymouri, Manouchehr, Badiee, Ali, Golmohammadzadeh, Shiva, Sadri, Kayvan, Akhtari, Javad, Mellat, Mostafa, Nikpoor, Amin Reza, Jaafari, Mahmoud Reza
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - metabolism; Biodistribution; Cell Line, Tumor; Cell Survival - drug effects; Cell Survival - physiology; Doxorubicin; Doxorubicin - administration & dosage; Doxorubicin - analogs & derivatives; Doxorubicin - metabolism; Drug Delivery Systems - methods; Drug Liberation; Female; Hexadecylphosphocholine; Liposome cell delivery; Liposomes; Mice; Mice, Inbred BALB C; Peptide Fragments - administration & dosage; Peptide Fragments - metabolism; Phosphorylcholine - administration & dosage; Phosphorylcholine - analogs & derivatives; Phosphorylcholine - metabolism; Polyethylene Glycols - administration & dosage; Polyethylene Glycols - metabolism; tat Gene Products, Human Immunodeficiency Virus - administration & dosage; tat Gene Products, Human Immunodeficiency Virus - metabolism; Tat-derived peptide; Tissue Distribution - drug effects; Tissue Distribution - physiology; Xenograft Model Antitumor Assays - methods
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2016.06.117

[Display omitted] We have investigated the co-addition of hexadecylphosphocholine (HePC) and a Tat derived peptide (Tat), coupled to Maleimide-PEG2000-DSPE pegylated liposomal doxorubicin (PLD) in many respects, including drug and liposome cellular delivery, drug release, biodistribution, in vivo cell delivery and antitumor activity. The liposomes were HePC-free and -containing liposomes, from which liposomes with 25, 50, 100 and 200 numbers of Tat/liposome were prepared. Similarly, DiI-C18 (3)-model liposomes (DiI-L and DiI-HePC-L) were prepared. HePC and Tat increased cellular delivery of Dox and cytotoxicity in B16F0 melanoma and C26 colon carcinoma cells. Tat enhanced liposome-cell interaction and caused Dox burst release. HePC and Tat reduced the serum retention time of liposomal Dox, slightly and dramatically, respectively. In comparison, Tat-liposomes enhanced Dox delivery to liver and spleen cells 3h post-injection. Likewise, Dox content of these tissues and tumor was lower at 24h. The naïve liposomes retarded tumor growth more effectively and their related median survival time of the treated C26 bearing BALB/c mice was longer than those of Tat-liposomes (MST>45days versus MST