ABSTRACT
CONTEXT: Nanocarriers possessing long-circulating abilities could take advantage of the pathophysiology of tumor vasculature to achieve spatial placement. To attain such qualities, the drug carriers should possess suitable physicochemical properties such as size and surface hydrophilicity. AIM: The aim of this study was to prepare poly(ε-caprolactone) nanoparticles (NPs) loaded with vinorelbine bitartrate (VB) and to modify its steric properties using polyethylene glycol and poloxamer. Furthermore, the influence of surface modification of NPs on their physicochemical and cell interactive properties was evaluated. MATERIALS AND METHODS: NPs were prepared by double emulsion solvent extraction-evaporation technique. The prepared NPs were evaluated for their physicochemical properties, in vitro protein adsorption and cell cytotoxicity. RESULTS AND DISCUSSION: The NPs were <250 nm with an entrapment efficiency ranging between 40% and 52%. The zeta potential of the NPs varied from -7.52 mV to -1.27 mV depending on the surface modification. The in vitro release studies exhibited a biphasic pattern with an initial burst release followed by controlled release of the drug over 72 h. The protein adsorption studies revealed that the ability to resist protein adsorption was influenced by the concentration of surface-modifying agents and the amount of proteins available for interaction. The surface-modified NPs produced cell cytotoxicity comparable to free VB at higher concentrations owing to sustained release of the drug into the cellular environment. CONCLUSION: The results emphasize that surface modification of nanocarriers is an essential and effective tool to dodge opsonization and phagocytosis in the physiological milieu.
ABSTRACT
The mononuclear phagocyte system (MPS) defends the body against the invasion of microorganisms by phagocytosis. In the presence of opsonins, the invading matter is readily recognized by phagocytes because of the interaction between receptors on the phagocytic cell surfaces and the modified conformation of opsonins. The particulate carriers, which are otherwise capable of optimizing drug delivery, are subjected to opsonization and phagocytosis by the MPS immediately following intravenous administration. These drug carriers should remain in the bloodstream in order to spatially locate the drug to the target site and temporally control the drug's release from there on; however, they are devastated by opsonization by serum proteins. Therefore, to restrict opsonization, which is critical for recognition of particulate carriers by the MPS, stealth devices have been developed by engineering the carriers' surface characteristics. Physicochemical properties that influence protein immunogenicity include particle size, surface charge, and surface hydrophobicity. Steric stabilization using polyethylene glycol (PEG) and polyethylene oxide (PEO) chains attached to the particle surface is principally effective in preventing the adsorption of serum opsonins. This article reviews the literature on the MPS and its development and functions, as well as approaches for designing long-circulating carrier particles. It also comprehensively reviews parameters affecting the steric characteristics of drug carriers, such as particle size, shape, surface charge, and surface affinity, including PEGylation of carriers.
