Comparative assessments of crucial factors for a functional ligand-targeted nanocarrier

Abstract

We previously developed a ligand-targeted liposome, referred to as a prohibitin-targeted nanoparticle (PTNP), for specifically delivering encapsulated drugs into vascular endothelial cells in adipose tissue. In this study, we explored the critical factors for the successful development and application of ligand-targeted nanocarriers through comparative assessments of PTNP prepared by the reverse-phase evaporation (REV) and lipid film hydration (HYD) methods with reference to physicochemical characteristics and in vivo and in vitro behavior. The in vivo delivery and therapeutic properties of HYD-PTNP were dramatically inferior to those of REV-PTNP, although the size, ζ-potential, fixed aqueous layer thickness and surface ligand density of the two preparations were similar. Circular dichroism spectral analyses revealed that the irreversible alteration in ligand conformation was caused by the organic solvent used to prepare the thin lipid film. In addition, perturbation of the ligand by the organic solvent resulted in a reduced internalization of PTNP into adipose endothelial cells. Alteration of the ligand conformation did not appear to affect the physicochemical characteristics of nanocarriers. Therefore, appropriate handling of ligands and appropriate evaluation of their conformations are critical for the successful development and application of such targeted nanocarriers.

Advances in an active and passive targeting to tumor and adipose tissues

“…In our recent study, no remarkable differences between the PTNPs prepared by the reverse-phase evaporation (REV) method [100] and the lipid film hydration (HYD) [101] methods were detected, including size, z-potentials, polydispersity index and drug encapsulation [102]. However, the PTNPs prepared by the REV method showed a broader distribution in the adipose tissue vasculature compared to the same sample prepared by the HYD method [102]. These findings indicate that the functional activity of the PTNP might be affected by the method used for their preparation, even though the welldefined physical properties remained similar.…”

“…These findings indicate that the functional activity of the PTNP might be affected by the method used for their preparation, even though the welldefined physical properties remained similar. We found that the conformation of the peptide ligand was irreversibly altered by its dissociation in an organic solvent such as chloroform and diisopropyl ether, resulting in a significant reduction in ligand--receptor interaction [102]. In many cases, functional and qualitative properties such as a secondary or tertiary structure in the peptide ligands would not appear in any of the physicochemical characteristics of the nanocarriers.…”

“…In many cases, functional and qualitative properties such as a secondary or tertiary structure in the peptide ligands would not appear in any of the physicochemical characteristics of the nanocarriers. Therefore, the adequate preparation of the ligand-targeted NPs and subsequent evaluation of the ligand properties could be one of the most important factors for the successful in vivo targeted delivery [102].…”

Liposome Microencapsulation for the Surface Modification and Improved Entrapment of Cytochrome c for Targeted Delivery

“…In our previous study, it was found that the exposure of PTP to organic solvents, such as CF, during the preparation of the PTNP by thin film hydration method (Bangham, Standish, & Watkins, 1965;Bangham, Standish, & Weissmann, 1965) caused an irreversible alteration of ligand conformation, resulting in the failure of the targeting activity of the PTP to prohibitin receptor (Hossen, Kajimoto, Tatsumi, Hyodo, & Harashima, 2014). To evaluate the functional ability of the peptide ligands of the PTNP prepared by the MCV method, sulforhodamine B-loaded PTNP was intravenously administered to mice.…”

Innovative Technologies in Nanomedicines: From Passive Targeting to Active Targeting/From Controlled Pharmacokinetics to Controlled Intracellular Pharmacokinetics

“…In order to proceed to the clinical application of PTNP, it is essential to establish a methodology for the large‐scale and sterile production of liposomes. However, in a recent study, we developed a method for preparing liposomes that could have a considerable influence on the targeting ability of PTNPs to adipose endothelial cells . Therefore, various methods for quality evaluation and standardization of nanomedicines also need to be simultaneously developed.…”