Solid lipid nanoparticles containing 7-ethyl-10-hydroxycamptothecin (SN38): Preparation, characterization, in vitro, and in vivo evaluations.
7-Ethyl-10-hydroxycamptothecin (SN38) is a biologically active metabolite of irinotecan. Due to the variability of irinotecan metabolism rate to SN38, and poor solubility of this compound in pharmaceutically acceptable solvents, SN38 has not been successfully used in the clinic. In the present study, we prepared solid lipid nanoparticle (SLN) formulations containing SN38 and evaluated the in vitro and in vivo efficacy of these nanoparticles. SLNs and PEGylated SLNs containing SN38 (SLN-SN38 and PEG-SLN-SN38) were prepared using ultrasonication technique. Nanoparticles were characterized for size, zeta potential, and drug encapsulation efficiency. In vitro cytotoxicity of these compounds was evaluated in two colorectal carcinoma cell lines, namely C-26 and HT-116. In vivo antitumor efficacy of the formulations was evaluated in C-26 xenograft tumor mice models. Mice survival was also explored through 60days post IV injection. Mean size of SLN-SN38 and PEG-SLN-SN38 was around 103 and 131nm, respectively. Polydispersity index (PDI) for all the formulations was around 0.2 and zeta potential was negative (-5 to -15mV). Nearly 90% of the drug was encapsulated in SLNs. SLN-SN38 and PEG-SLN-SN38 compared to irinotecan were significantly more toxic to C-26 and HT-116 cell lines after 48h of exposure. Calculation of IC50 suggests higher sensitivity of HT-116 cells than C-26 cells to SLN-SN38 and PEG-SLN-SN38. Tumor inhibitory efficacy presented the highest efficacy in SLN-SN38. However, both SLN-SN38 and PEG-SLN-SN38 carriers showed higher efficiency to inhibit tumors compared to irinotecan (25mg/kg).
School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Navid
N
Mosallaei
School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Asma
A
Mahmoudi
Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT, USA; Utah Center for Nanomedicine, Nano Institute of Utah, University of Utah, Salt Lake City, UT, USA; Department of Bioengineering, University of Utah, Salt Lake City, UT, USA.
Hamidreza
H
Ghandehari
Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT, USA; Utah Center for Nanomedicine, Nano Institute of Utah, University of Utah, Salt Lake City, UT, USA; College of Pharmacy, Roseman University of Health Sciences, South Jordan, UT, USA.
Venkata Kashyap
VK
Yellepeddi
School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; Biotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Mahmoud Reza
MR
Jaafari
School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: malaekehb@mums.ac.ir.
Bizhan
B
Malaekeh-Nikouei
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000737:chemistry; D045744:Cell Line, Tumor; D064593:Heterografts; D006801:Humans; D066298:In Vitro Techniques; D000077146:Irinotecan; D008055:Lipids / Q000737:chemistry*; D051379:Mice; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D015996:Survival Rate
D000972:Antineoplastic Agents, Phytogenic; D008055:Lipids; D000077146:Irinotecan; D002166:Camptothecin
7-Ethyl-10-hydroxycamptothecin (SN38); Chemotherapy; Cytotoxicity; Irinotecan; Solid lipid nanoparticles (SLNs)