Abstract
Lipid nanocapsules (LNC) based on a core-shell structure consisting of an oil-filled core with a surrounding polymer layer are known to be promising vehicles for the delivery of hydrophobic drugs in the new therapeutic strategies in anti-cancer treatments. The present work has been designed as basic research about different LNC systems. We have synthesized—and physico-chemically characterized—three different LNC systems in which the core was constituted by olive oil and the shell by different phospholipids (phosphatidyl-serine or lecithin) and other biocompatible molecules such as Pluronic® F68 or chitosan. It is notable that the olive-oil-phosphatidyl-serine LCN is a novel formulation presented in this work and was designed to generate an enriched carboxylic surface. This carboxylic layer is meant to link specific antibodies, which could facilitate the specific nanocapsule uptake by cancer cells. This is why nanoparticles with phosphatidyl-serine in their shell have also been used in this work to form immuno-nanocapsules containing a polyclonal IgG against a model antigen (C-reactive protein) covalently bounded by means of a simple and reproducible carbodiimide method. An immunological study was made to verify that these IgG-LNC complexes showed the expected specific immune response. Finally, a preliminary in vitro study was performed by culturing a breast-carcinoma cell line (MCF-7) with Nile-Red-loaded LNC. We found that these cancer cells take up the fluorescent Nile- Red molecule in a process dependent on the surface properties of the nanocarriers.
Highlights
Nanomedicine, an emerging new field created by the fusion of nanotechnology and medicine, has become one of the most promising pathways for developing effective targeted therapies with particular impact on oncology
In addition to measuring the colloidal stability of our nanocapsules with NaCl and CaCl2, we evaluated stability in phosphate buffer saline (PBS) and in Dulbecco’s Modified Eagle’s Medium (DMEM) supplemented with fetal bovine serum by monitoring the variation of optical absorbance of the nanocapsules as a function of time
System, in which the shell was enriched by carboxyl groups supplied by phosphatidyl-serine molecules, was compared to two standard Lipid nanocapsules (LNC) systems: an anionic one formed by Epikuron and Pluronic® F68, and a cationic system coated by chitosan
Summary
Nanomedicine, an emerging new field created by the fusion of nanotechnology and medicine, has become one of the most promising pathways for developing effective targeted therapies with particular impact on oncology. LNC represent an important class of nanocarriers capable of efficiently encapsulating and delivering a variety of drugs, their typical pathway to act on cancer tissues is through the so-called enhanced permeability and retention effect This means passive targeting with non-specific delivery and the inability to cross several biological barriers based on molecular recognition processes [7,10,15]. These tailored-LNCs would deliver a given drug towards a targeted malignant tumor [4] Within this scenario, the main objective of the present work focuses on developing a simple, reproducible and non-expensive procedure to synthesize LNCs systems, paying special attention to designing nanocapsules in which antibody molecules can be covalently attached on the surface. Nile-Red-loaded lipid nanocapsules were prepared to make a quantitative study of particle uptake by a breast-carcinoma cell line (MCF-7), Nile-Red being a commercially available hydrophobic fluorescent molecule
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