Biodegradable nanoparticles designed for drug delivery: The number of nanoparticles impacts on cytotoxicity

Abstract

Nanostructured drug delivery systems are based on biocompatible and biodegradable components. Composition, size and membrane surface properties are characteristics that may influence cell viability in cytotoxicity assays. In this work, four nanostructured systems commonly used for drug delivery were prepared and cytotoxicity was evaluated on human lymphocytes and Balb/c 3T3 fibroblasts. The hemolytic potential was also investigated. Polymeric nanocapsules (NC) and nanospheres (NS), nanostructured lipid carriers (NLC) and liposomes were prepared and characterized for size, distribution, zeta potential and number per volume of the colloidal dispersion. Cell viability was evaluated, 24 and 48h, by MTT and neutral red assays (NR). Cells were incubated with each particle in eight different dilutions varying from 2.1×10(4) to 2.1×10(11)particles/mL. Diameter of nanoparticles was between 130 and 200nm, all samples exhibited narrow size distribution (polydispersity index below 0.1) and zeta potential varied from -6.8 to -19.5mV. NC, NS and NLC reduced cell viability in a dilution dependent manner. For these nanoparticles, the higher number of particles induced cell death for both cell types. Liposomes did not cause loss of cell viability even at the highest number of particles. Results suggest that, depending on the kind of nanoparticle, the number of particles in the dispersion can negatively influence cell viability in pre-clinical drug development.

Assessing the axonal translocation of CeO2 and SiO2 nanoparticles in the sciatic nerve fibers of the frog: an ex vivo electrophysiological study

“…In other in vitro studies, it has been shown that the number of NPs impacts cytotoxicity. 39 We have also demonstrated that electrical activation is required for effective transportation. In similar ex vivo frog sciatic nerve experiments, repetitive action potentials have been shown to retard mitochondrial motility through nodes of Ranvier by reducing the number of mobile mitochondria, reducing the velocity, and increasing the pause duration in a Ca 2+ -dependent manner.…”

Nanostructured Lipid Carriers: Versatile Oral Delivery Vehicle

“…In a more defined study, it was observed that the toxicity of NLCs was dependent on the number of NLCs (particles/ml), in other words, various concentrations of NLCs (particles/ml) were incubated with lymphocytes and it was observed that 2.1 × 10 11 particles/ml lead to decreased viability of cells (55%). NLCs also showed concentration-dependent cytotoxic effects and hemolytic activity [104]. In an interesting study, various lipids and surfactants to be employed for the formulation of NLCs were preliminarily screened via cytotoxicity assay on most appropriate cell lines for validation of basal toxicity (BALB/c 3T3) with the aim to select the formulation ingredients with minimal cytotoxicity [106].…”

From micro- to nanostructured implantable device for local anesthetic delivery

“…The nanosystems, indeed, were demonstrated to improve intracellular penetration. [69][70][71] In order to have a controlled and reliable LA release, the drug would be encapsulated in a biocompatible and biodegradable nanostructured system, to minimize tissue reaction and to control precisely the rate of drug delivery, which has to be comparable with the rate of generation of nontoxic de gradation products. In fact, an initial uncontrolled large dose of drug release could be lethal for the organism and therefore must be avoided.…”

“…14,72 Moreover, LA nanoencapsulation increases the drug's efficacy, specificity, tolerability, and therapeutic index. 69 The LA release kinetics and the drug loading efficiency are influenced by the size of the system. Larger particles could load a larger amount of drug, leading to a longer block duration and thus a longer effect.…”