International Journal of Nanomedicine (May 2021)
Preparation, Pharmacokinetics, and Antitumor Potential of Miltefosine-Loaded Nanostructured Lipid Carriers
Abstract
Guo Yu, 1 Zakir Ali, 2 Anam Sajjad Khan, 2 Kalim Ullah, 3 Humzah Jamshaid, 2 Alam Zeb, 4 Muhammad Imran, 4 Sadia Sarwar, 4 Han-Gon Choi, 5 Fakhar ud Din 2 1Department of Head and Neck Breast, Xinxiang Central Hospital, Xinxiang City, Henan Province, 453000, People’s Republic of China; 2Nanomedicine Research Group, Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, 45320, Pakistan; 3Department of Zoology, Kohat University of Science & Technology, Kohat, Khyber Pakhtunkhwa, Pakistan; 4Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan; 5College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, South KoreaCorrespondence: Fakhar ud Din Tel +92 512-90644314Fax +92 512-90644144Email [email protected] Choi Email [email protected]: The purpose of this study was to investigate the suitability of nanostructured lipid carriers (NLCs) loaded with miltefosine (HePC) as an anticancer drug for the treatment of breast cancer.Methods: HePC-NLCs were prepared using a microemulsion technique and then evaluated for particle size, polydispersity index (PDI), incorporation efficiency, in vitro release of entrapped drug, and hemolytic potential. Furthermore, pharmacokinetic, biodistribution, and liver toxicity analyses were performed in Sprague–Dawley rats, and antitumor efficacy was evaluated in Michigan Cancer Foundation-7 (MCF-7) and squamous cell carcinoma-7 (SCC-7) cells in vitro and in tumour-bearing BALB/c mice in vivo. Advanced analyses including survival rate, immunohistopathology, and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assays were performed to evaluate apoptosis in vivo.Results: The average particle size of the HePC-NLCs was 143 ± 16 nm, with a narrow PDI (0.104 ± 0.002), and the incorporation efficiency was found to be 91 ± 7%. The NLCs released HePC in a sustained manner, and this release was significantly lower than that of free drug. The in vitro hemolytic assay demonstrated a significantly reduced hemolytic potential (∼ 9%) of the NLCs compared to that of the test formulations. The HePC-NLCs demonstrated enhanced pharmacokinetic behaviour over free drug, including extended blood circulation and an abridged clearance rate in rats. Furthermore, the HePC-NLCs exhibited higher cytotoxicity than the free drug in MCF-7 and SCC-7 cells. Moreover, the HePC-NLCs showed significantly enhanced (P < 0.005) antitumor activity compared to that of the control and free drug-treated mouse groups. Tumour cell apoptosis was also confirmed, indicating the antitumor potential of the HePC-NLCs.Conclusion: These findings demonstrate the ability of NLCs as a drug delivery system for enhanced pharmacokinetic, antitumor, and apoptotic effects, most importantly when loaded with HePC.Keywords: breast cancer, miltefosine, nano lipid carriers, bioavailability, pharmacokinetics, antitumor efficacy
