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In this review we will report on recent advanced in polyelectrolyte capsules for targeted drug delivery (eg of growth factor inhibitor) against epatocarcinoma. Degradable polyelectrolyte multilayers capsules (PMCs) are of particular interest for cancer therapy since under physiological conditions they can be enzymatically degraded upon cell interaction. Small bioactive molecules such as TGFBeta inhibitors can be incorporated inside them. Nano-to-microscale delivery systems can enhance efficacy at single cell level for targeted therapy. Layer-by-layer (LbL) self-assembled capsules are novel carriers maximizing drug administration and improving antimetastatic activity of TGF-Beta inhibitors in Hepatocellular Carcinoma (HCC). © 2012 Bentham Science Publishers.

The increasingly widespread use of engineered nanomaterials in many applications increases the need to understand the mechanisms behind their toxicity [...]

Calcium carbonate (CaCO3) particles represent an appealing choice as a drug delivery system due to their biocompatibility, biodegradability, simplicity and cost-effectiveness of manufacturing, and stimulus-responsiveness. Despite this, the synthesis of CaCO3 particles with controlled size in the nanometer range via a scalable manufacturing method remains a major challenge. Here, by using a co-precipitation technique, we investigated the impact on the particle size of different synthesis parameters, such as the salt concentration, reaction time, stirring speed, and temperature. Among them, the salt concentration and temperature resulted in having a remarkable effect on the particle size, enabling the preparation of well-dispersed spherical nanoparticles with a size below 200 nm. Upon identification of optimized synthesis conditions, the encapsulation of the antitumoral agent resveratrol into CaCO3 nanoparticles, without significantly impacting the overall size and morphology, has been successfully achieved.

Hepatic fibrosis (HF) is a major cause of liver-related disorders and together with cancer-associated fibroblasts can favor liver cancer development by modulating the tumor microenvironment. Advanced HF, characterized by an excess of extracellular matrix (ECM), is mediated by TGF- β1, that activates hepatic stellate cells (HSCs) and fibroblasts. A TGF-β1 receptor inhibitor, LY2157299 or Galunisertib (GLY), has shown promising results against chronic liver progression in animal models, and we show that it can be further improved by enhancing GLYs bioavailability through encapsulation in polymeric polygalacturonic-polyacrylic acid nanomicelles (GLY-NMs). GLY-NMs reduced HF in an in vivo rat model of liver fibrosis induced by intraperitoneal injection of CCl4 as shown by the morphological, biochemical, and molecular biology parameters of normal and fibrotic livers. Moreover, GLY-NM was able to induce recovery from HF better than free GLY. Indeed, the encapsulated drug reduces collagen deposition, hepatic stellate cells (HSCs) activation, prevents fatty degeneration and restores the correct lobular architecture of the liver as well as normalizes the serum parameters and expression of the genes involved in the onset of HF. In summary, GLY-NM improved the pharmacological activity of the free TGF- β1 inhibitor in the in vivo HF treatment and thus is a candidate as a novel therapeutic strategy.

Inorganic materials, in particular nanoclays and silica nanoparticles, have attracted enormous attention due to their versatile and tuneable properties, making them ideal candidates for a wide range of biomedical applications, such as drug delivery. This review aims at overviewing recent developments of inorganic nanoparticles (like porous or mesoporous silica particles) and different nano-clay materials (like montmorillonite, laponites or halloysite nanotubes) employed for overcoming the blood brain barrier (BBB) in the treatment and therapy of major brain diseases such as Alzheimer's, Parkinson's, glioma or amyotrophic lateral sclerosis. Recent strategies of crossing the BBB through invasive and not invasive administration routes by using different types of nanoparticles compared to nano-clays and inorganic particles are overviewed.

Halloysite nanotubes (HNTs) are hollow clay nanotubes in the nanometer size range, made up of double-layered aluminum silicate mineral layers. HNTs represent an extremely versatile, safe, and biocompatible nanomaterial, used in a wide range of applications in biomedicine and nanomedicine. For example, they are used as transporters for the controlled release of drugs or genes, in tissue engineering, in the isolation of stem cells and cancer cells, and in bioimaging. Consequently, the assessment of the biocompatibility of HNTs has acquired considerable importance. In recent years, HNT composites have attracted attention due to their improved biocompatibility, compared to HNTs, suggesting potential for applications in tissue engineering or as vehicles for drugs or genes. In this review, recent advances in the application of HNTs and HNT composites in biomedicine are discussed to provide a valuable guide to scientists in the design and development of viable, functional bio-devices for biomedical applications.

Natural halloysite clay nanotubes (HNTs) are versatile inorganic reinforcing materials for creating hybrid composites. Upon doping HNTs with polymers, coating, or loading them with bioactive molecules, the production of novel nanocomposites is possible, having specific features for several applications. To investigate HNTs composites nanostructures, AFM is a very powerful tool since it allows for performing nano-topographic and morpho-mechanical measurements in any environment (air or liquid) without treatment of samples, like electron microscopes require. In this review, we aimed to provide an overview of recent AFM investigations of HNTs and HNT nanocomposites for unveiling hidden characteristics inside them envisaging future perspectives for AFM as a smart device in nanomaterials characterization.

In the last decade, the onset of neurodegenerative (ND) diseases is strongly widespread due to the age increase of the world population. Despite the intensive investigations boosted by the scientific community, an efficacious therapy has not been outlined yet. The drugs commonly used are only able to relieve symptom severity; following their oral or intravenous administration routes, their effectiveness is strictly limited due to their low ability to reach the Central Nervous System (CNS) overcoming the Blood Brain Barrier (BBB). Starting from these assumptions, the engineered-nanocarriers, such as lipid-nanocarriers, are suitable agents to enhance the delivery of drugs into the CNS due to their high solubility, bioavailability, and stability. Liposomal delivery systems are considered to be the ideal carriers, not only for conventional drugs but also for neuroprotective small molecules and green-extracted compounds. In the current work, the LP-based drug delivery improvements in in vivo applications against ND disorders were carefully assessed.

In this work, tunable nonwoven mats based on poly(3-hydroxybutyrate) (PHB) and type I collagen (Coll) were successfully produced by electrospinning. The PHB/Coll weight ratio (fixed at 100/0, 70/30, and 50/50, resp.) was found to control the morphological, thermal, mechanical, and degradation properties of the mats. Increasing collagen amounts led to larger diameters of the fibers (in the approximate range 600–900 nm), while delaying their thermal decomposition (from 245°C to 262°C). Collagen also accelerated the hydrolytic degradation of the mats upon incubation in aqueous medium at 37°C for 23 days (with final weight losses of 1%, 15%, and 23% for 100/0, 70/30, and 50/50 samples, resp.), as a result of increased mat wettability and reduced PHB crystallinity. Interestingly, 70/30 meshes were the ones displaying the lowest stiffness (~116 MPa; p<0.05 versus 100/0 and 50/50 meshes), while 50/50 samples had an elastic modulus comparable to that of 100/0 ones (~250 MPa), likely due to enhanced physical crosslinking of the collagen chains, at least at high protein amounts. All substrates were also found to allow for good viability and proliferation of murine fibroblasts, up to 6 days of culture. Collectively, the results evidenced the potential of as-spun PHB/Coll meshes for tissue engineering applications.

The EMT phenomenon is based on tumour progression. The cells lose their physiologic phenotype and assumed a mesenchymal phenotype characterized by an increased migratory capacity, invasiveness and high resistance to apoptosis. In this process, RHO family regulates the activation or suppression of ROCK (Rho-associated coiled-coil containing protein kinase) which in turn regulates the cytoskeleton dynamics. However, while the biochemical mechanisms are widely investigated, a comprehensive and careful estimation of biomechanical changes has not been extensively addressed. In this work, we used a strong ROCK inhibitor, Y-27632, to evaluate the effects of inhibition on living breast cancer epithelial cells by a biomechanical approach. Atomic Force Microscopy (AFM) was used to estimate changes of cellular elasticity, quantified by Young's modulus parameter. The morphometric alterations were analyzed by AFM topographies and Confocal Laser Scanning Microscopy (CLSM). Our study revealed a significant modification in the Young's modulus after treatment, especially as regards cytoskeletal region. Our evidences suggest that the use of Y-27632 enhanced the cell rigidity, preventing cell migration and arrested the metastasization process representing a potential powerful factor for cancer treatment.

Nowadays, there is strong interest in the development of smart inorganic nanostructured materials as tools for targeted delivery in cancer cells. We proposed a novel synthetic procedure of calcium carbonate nanocrystals (NCs) and their use as drug delivery systems, studying the physical chemical properties and the in vitro interaction with two model cancer cells. Pure and thermodynamically stable CaCO3 NCs in calcite phase were synthesized by a readily and feasible method, easily scalable, that allows the control of NCs shape and size without any surfactant use. CaCO3 NCs were extensively investigated by Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS), X-ray Diffraction (XRD), Raman spectroscopy and Brunauer-Emmett-Teller analysis (BET). To deeper investigate their possible use as nanovectors for drug cancer therapies, CaCO3 NCs biocompatibility (by MIT assay), cell interaction and internalization were studied in in vitro experiments on HeLa and MCF7 cell lines. Confocal and transmission electron microscopies were used to monitor and evaluate NCs-cell interaction and cellular uptake. Data here reported demonstrated that synthesized NCs readily penetrate HeLa and MCF7 cells. NCs preferentially localize inside the cytoplasm, but were also found into mitochondria, nucleus and lysosomes. This study suggests that synthesized CaCO3 NCs are good candidates as effective intracellular therapeutic delivery system. (C) 2016 The Society of Powder Technology Japan. Published by Elsevier B.V. and The Society of Powder Technology Japan. All rights reserved.

Halloysite clay nanotubes (HNTs) are natural materials with a characteristic hollow tubular structure in the nanometer range. Owing to this feature, they were found to be a suitable nanosized container for the loading of biologically active molecules like biocides and drugs. Also, HNTs have been reported to be of potential interest for other biological applications, such as gene delivery carriers, ultrasound contrast agents, cancer therapy, and stem cells isolation. Therefore, biocompatibility of halloysite represents one the main requisites for the employment of HNTs for clinical purposes. Here we present a study aimed at assessing HNTs biocompatibility before and after their surface coating with poly(ethylene glycol) (PEG), a polymer which has been reported to increase biocompatibility, to prolong circulation time, and to prevent protein adsorption and aggregation in biological environments. The dose- and time-dependent cytotoxicity of noncoated and PEG-coated HNTs obtained was evaluated in vitro by MTT cell viability assay carried out on both HeLa and HepG2 cells, two different human cancer cell lines. Binding and uptake of nanotubes were also analyzed at ultrastructural level by transmission electron microscopy. Interestingly, the results obtained showed that both the HNTs tested were actively taken up by the cells but, while noncoated nanotubes exhibited significant concentration- and time-dependent toxicity, PEG-coated HNTs were found to be highly biocompatible, being then suitable candidates for biomedical applications.

Halloysite is a nanostructured clay mineral with hollow tubular structure, which has recently found an important role as delivery system for drugs or other active molecules. One of these is curcumin, main constituent in the rhizome of the plant Curcuma Longa, with a series of useful pharmacological activities, hindered by its poor bioavalaibility and solubility in water. In this study, Halloysite clay nanotubes (HNTs) were characterized in terms of both structure and biocompatibility and they were used for curcumin delivery to cancer cells. The performed 3-(4, 5-dimethythiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay showed that HNTs have a high biocompatibility, also when coated with polymers, while curcumin is highly toxic for cancer cells. The release kinetics of curcumin from HNTs was investigated by the dialysis bag method, showing a slow and constant release of the drug, which can be further controlled by adding layers of polyelectrolytes to the external surface of the tubes. Successful polymer coating was followed by Zeta potential. The Trypan Blue assay showed a cytotoxic effect of loaded HNTs, proportional to the concentration of tubes and the incubation time. Successful HNTs uptake by breast cancer cells was demonstrated by Confocal Laser Scanning Microscopy images. All results indicate that HNTs are a promising carriers for polyphenol delivery and release.

The unique physico-chemical properties of silver nanoparticles (AgNPs) make them a powerful tool in many fields, ranging from cosmetics, biomedicals, household products, and wound dressing. Several evidences suggest the strong toxicity of AgNPs both in vitro and in vivo, but few data are available to full understanding of their adverse effects on cellular components and cytoskeleton. In this work, we assessed the toxicity of citrate-capped AgNPs on cortical actin and organelles, namely mitochondria and lysosomes, on epithelial breast cancer cells (MCF-7). The impact of AgNPs on cells was firstly evaluated in term of viability, oxidative stress, mitochondria membrane potential alteration, and apoptosis activation. Afterwards, we carefully estimated the qualitative and quantitative morphological alterations of cortical F-actin and organelles by confocal microscopy and specific software tools, coupled with a biomechanical analysis by atomic force microscopy (AFM). This multidisciplinary approach, which combines the standard biological assays with systematic morphometric and biomechanical analysis on cells, permits to understand at different levels the intracellular response elicited by AgNPs in order to provide new scenarios in toxicity assessment.

LY2157299 (LY), which is very small molecule bringing high cancer diffusion, is a pathway antagonist against TGFβ. LY dosage can be diluted by blood plasma, can be captured by immune system or it might be dissolved during digestion in gastrointestinal tract. The aim of our study is to optimize a “nano-elastic” carrier to avoid acidic pH of gastrointestinal tract, colon alkaline pH, and anti-immune recognition. Polygalacturonic acid (PgA) is not degradable in the gastrointestinal tract due to its insolubility at acidic pH. To avoid PgA solubility in the colon, we have designed its conjugation with Polyacrylic acid (PAA). PgA-PAA conjugation has enhanced their potential use for oral and injected dosage. Following these pre-requisites, novel polymeric nano-micelles derived from PgA-PAA conjugation and loading LY2157299 are developed and characterized. Efficacy, uptake and targeting against a hepatocellular carcinoma cell line (HLF) have also been demonstrated.

TGFβ1 pathway antagonists have been considered promising therapies to attenuate TGFβ downstream signals in cancer cells. Inhibiting peptides, as P-17 in this study, are bound to either TGFβ1 or its receptors, blocking signal transduction. However, for efficient use of these TGFβ1antagonist as target therapeutic tools, improvement in their delivery is required. Here, a plasmid carrying specific shDNA (SHT-DNA), small interfering RNA (siRNA), and the peptide (P-17) were loaded separately into folic acid (FA)-functionalized nano-carriers made of Bovine Serum Albumin (BSA). The two building blocks of the carrier, (BSA and FA) were used because of the high affinity of albumin for liver and for the overexpression of folate receptors on the membrane of hepatocellular carcinoma cells. The empty and the encapsulated carriers were thoroughly investigated to characterize their structure, to evaluate the colloidal stability and the surface functionalization. The entrapment of SHT-DNA, siRNA and P-17, respectively, was demonstrated by morphological and quantitative analysis. Finally, cellular studies were performed to assess the targeting efficiency of the hybrid carriers. These vectors were used because of the high affinity of albumin for liver and for the overexpression of folate receptors on the membrane hepatocellular carcinoma cells. The empty and the encapsulated carriers were thoroughly investigated to characterize their structure, to evaluate the colloidal stability and the surface functionalization. The entrapment of SHT-DNA, siRNA and P-17, respectively, was demonstrated by morphological and quantitative analysis. Graphical Abstract: A novel fabrication of Hybrid Polymeric-Protein Nano-Carriers (HPPNC) for delivering TGF β1 inhibitors to HCC cells has been developed. SHT-DNA, siRNA and P-17 have been successfully encapsulated. TGF β1 inhibitors-loaded HPPNC were efficiently uptaken by HLF cells. [InlineMediaObject not available: see fulltext.].

Polyelectrolyte multilayer (PEM) capsules engineered with active elements for targeting, labeling, sensing and delivery hold great promise for the controlled delivery of drugs and the development of new sensing platforms. PEM capsules composed of biodegradable polyelectrolytes are fabricated for intracellular delivery of encapsulated cargo (for example peptides, enzymes, DNA, and drugs) through gradual biodegradation of the shell components. PEM capsules with shells responsive to environmental or physical stimuli are exploited to control drug release. In the presence of appropriate triggers (e.g., pH variation or light irradiation) the pores of the multilayer shell are unlocked, leading to the controlled release of encapsulated cargos. By loading sensing elements in the capsules interior, PEM capsules sensitive to biological analytes, such as ions and metabolites, are assembled and used to detect analyte concentration changes in the surrounding environment. This Review aims to evaluate the current state of PEM capsules for drug delivery and sensing applications. © 2014 Elsevier B.V.

Fluoro-magnetic nanoparticles play an important role in biomedical applications since their size and concentration in tumors allow a very high resolution and an accurate mapping of lesions. Fluorescein isothiocyanate (FITC) has been entrapped inside crystals of magnetic nanoparticles (MNPs) during crystallization. This causes changes of nanoparticle crystal architecture towards elongated rods. TEM and SEM-EDX show elongated crystals with high iron concentration. The intensity of fluoro-MNP fluorescence was detected by fluorescence spectrophotometry and confocal microscopy. The benzene ring structure of FITC and its carboxylic group were clearly detected in the fluoro-MNP spectrum by using FTIR, compared to MNPs prepared in the absence of FITC. Rods were functionalized by hydrogel cross-linking structure (PEG-CMC) onto the fluoro-MNPs surface by using alternate layer-by-layer (LbL) adsorption. These hydrogel properties are used as a preserver for protein delivery. ALK1fc as specific TGFβ1 inhibitor, was encapsulated inside (PEG-CMC) layers during LbL assembly. Zeta potential measurement, X-ray diffraction and SDS PAGE-silver staining results confirmed the encapsulation of ALK1fc. The efficiency of encapsulated ALK1fc was quantified by immunofluorescence assay against localization of TGFβ1. Stained TGFβ1 appeared a purple color and is distributed in the cytoplasm of untreated HLF (a liver cancer invasive cell line), whereas it disappeared in a HLF sample treated with encapsulated ALK1fc.

Aim of this work was to investigate the automatic echographic detection of an experimental drug delivery agent, halloysite clay nanotubes (HNTs), by employing an innovative method based on advanced spectral analysis of the corresponding "raw" radiofrequency backscatter signals. Different HNT concentrations in a low range (5.5-66 × 10(10) part/mL, equivalent to 0.25-3.00 mg/mL) were dispersed in custom-designed tissue-mimicking phantoms and imaged through a clinically-available echographic device at a conventional ultrasound diagnostic frequency (10 MHz). The most effective response (sensitivity = 60%, specificity = 95%), was found at a concentration of 33 × 10(10) part/mL (1.5 mg/mL), representing a kind of best compromise between the need of enough particles to introduce detectable spectral modifications in the backscattered signal and the necessity to avoid the losses of spectral peculiarity associated to higher HNT concentrations. Based on theoretical considerations and quantitative comparisons with literature-available results, this concentration could also represent an optimal concentration level for the automatic echographic detection of different solid nanoparticles when employing a similar ultrasound frequency. Future dedicated studies will assess the actual clinical usefulness of the proposed approach and the potential of HNTs for effective theranostic applications.

A smart nanocarrier system for cancer therapy, based on a recently developed technique for preparing pure nanometric calcium carbonate (CaCO 3 ), was studied. Different approaches were used to obtain sustained release of cisplatin : at first, pure CaCO 3 nanoparticles were evaluated as carriers, then the nanoparticles were functionalized with polymer or silanes, and finally they were employed as a substrate to build layer by layer (LbL) self-assembled polyelectrolyte nanocapsules. Loading efficiency and release kinetics were measured. The best loadings were obtained with the LbL nanocapsules, allowing for high loading efficiency and the possibility of controlling the release rate of the drug. The behavior of all the carriers was evaluated on four neoplastic cell lines, representative of different types of neoplastic disease, namely MCF-7 (breast cancer), SKOV-3 (ovarian cancer), HeLa (cervical cancer) and CACO-2 (human epithelial colorectal adenocarcinoma). Negligible cytotoxicity of the nanoparticles, functionalized nanoparticles, and nanocapsules was observed in experiments with all cell lines. Nanocapsules were functionalized with fluorescein isothiocyanate (FITC) in order to track their kinetic of internalization and localization in the cell line by confocal laser scanning microscopy (CLSM). The cytotoxicity of the loaded capsules was evaluated, showing cell survival rates close to those expected for non-encapsulated cisplatin at the same nominal concentration.

Halloysite clay Nanotubes (HNTs) are nanomaterials composed of double layered aluminosilicate minerals with a hollow tubular structure in the submicron range. They are characterized by a wide range of applications in anticancer therapy as agent delivery. In this work we aim to investigate the automatic detection features of HNTs through advanced quantitative ultrasound imaging employing different concentrations (3-5 mg/mL) at clinical conventional frequency, i.e. 7 MHz. Different tissue mimicking samples of HNT containing agarose gel were imaged through a commercially available echographic system, that was opportunely combined with ultrasound signal analysis research platform for extracting the raw ultrasound radiofrequency (RF) signals. Acquired data were stored and analyzed by means of an in-house developed algorithm based on wavelet decomposition, in order to identify the specific spectrum contribution of the HNTs and generate corresponding image mapping. Sensitivity and specificity of the HNT detection were quantified. Average specificity (94.36%) was very high with reduced dependency on HNT concentration, while sensitivity showed a proportional increase with concentration with an average of 46.78%. However, automatic detection performances are currently under investigation for further improvement taking into account image enhancement and biocompatibility issues.

Halloysite nanotubes (HNTs) are nanomaterials composed of double layered aluminosilicate minerals characterized by a wide range of medical applications. Nonetheless, systematic investigations of their imaging potential are still poorly documented. This paper shows a parametric assessment of the effectiveness of HNTs as scatterers for safe ultrasound (US)-based molecular imaging. Quantitative evaluation of average signal enhancement produced by HNTs with varying set up configuration was performed. The influence of different levels of power (20%, 50%, and 80%) of the signal emitted by clinical equipment was determined, to assess the efficacy of different HNT concentrations (1.5, 3, and 5 mg/mL) at conventional ultrasonic frequencies (5.7-7 MHz), even in case of specific limitation regarding US mechanical interaction with target tissues. Different samples of HNT containing agarose gel were imaged through a commercially available echographic system and acquired data were processed through a dedicated prototypal platform to extract the average ultrasonic signal amplitude. The rate of signal enhancement achieved by different concentration values was quantified and the contribution of frequency increment was separately evaluated. Despite influencing the level of mechanical excitation on HNTs and tissues, our results demonstrated how increasing the power of the emitted signal negatively affected the measured backscatter. Conversely, noticeable improvements in signal backscatter could be achieved incrementing HNT concentration and the echographic frequency employed; specifically the signal enhancement over the used concentration range could be improved by averagely 20%, corresponding to 4.86 ± 0.80 (a.u.), when employing the higher value of echographic frequency. © 2013 IEEE.

Halloysite Nanotubes (HNTs) are nanomaterials composed of double layered aluminosilicate minerals with a predominantly hollow tubular structure in submicron range. HNTs are characterized by a wide range of applications in anticancer therapy, sustained agent delivery, being particularly interesting because of their tunable release rates and fast adsorption rates. However systematic investigations of their acoustic properties are still poorly documented. This paper shows a quantitative assessment of the effectiveness of HNTs as scatterers at conventional ultrasonic frequencies (5.7 -7 MHz) in low range of concentrations (1.5-5 mg/mL). Different samples of HNT (diameter: 40-50 nm; length: 0.5 to 2 microns, empty lumen diameter: 15-20 nm) containing agarose gel were imaged through a commercially available echographic system and acquired data were processed through a dedicated prototypal platform in order to extract the average ultrasonic signal amplitude associated to the considered sample. Relationships have been established among backscatter, HNT concentration and the employed echographic frequency. Our results demonstrated that improvement in image backscatter could be achieved incrementing HNT concentration, determining a non-linear signal enhancement due to the fact that they are poly-disperse in length. On the other hand the effect of different echographic frequencies used was almost constant at all concentrations, specifically using higher values of echographic frequency allows yielding a signal enhanced of a factor 1.75±0.26. © 2013 IEEE.

Halloysite is natural aluminosilicate clay with hollow tubular structure which allows loading with low soluble drugs using their saturated solutions in organic solvents. Resveratrol, a polyphenol known for having antioxidant and antineoplastic properties, is loaded inside these clay nanotubes lumens. Release time of 48 h is demonstrated. Spectroscopic and ζ-potential measurements are used to study the drug loading/release and for monitoring the nanotube layer-by-layer (LbL) coating with polyelectrolytes for further release control. Resveratrol-loaded clay nanotubes are added to breast cell cultures for toxicity tests. Halloysite functionalization with LbL polyelectrolyte multilayers remarkably decrease nanotube self-toxicity. MTT measurements performed with a neoplastic cell lines model system (MCF-7) as function of the resveratrol-loaded nanotubes concentration and incubation time indicate that drug-loaded halloysite strongly increase of cytotoxicity leading to cell apoptosis.

The internalisation efficiency and cytotoxicity of polymeric microparticles and capsules were studied for three different adherent cell lines: HeLa (human cervice cancer), MCF-7 (human breast cancer) and B104 (murine neuroblastoma). Microparticles of colloidal CaCO3 cores coated with either layerby- layer self-assembled oppositely charged biosynthetic (PSS\PAH) or biodegradable (DXS\PRM) polyelectrolytes and hollow capsules thereof, obtained upon removal of the CaCO3 cores by EDTA, were fabricated. Fluorescent-labeled polymer layers coated onto CaCO3 cores were employed for evaluating cell uptake efficiency. Confocal laser scanning microscopy was used to confirm dissolution of preformed biodegradable multilayers. Cellular viability for all type of colloidal entities was preserved, indicating safety and tolerability of the potential drug carriers.