Biodegradable Nanospheres Research Articles

Formulation and characterization of 5-fluorouracil and metformin biodegradable nanospheres for treating colon cancer

BackgroundCancer and diabetes mellitus are quite common diseases found together worldwide. A considerable amount of evidence is available for the rapid development and presentation of various types of cancer in the type 2 diabetes mellitus (DM2) population as compared with the population without diabetes. The objective of the study is to formulate and evaluate 5-fluorouracil (5-FU) and metformin (MET) nanoparticles (NPs) and to establish the characteristic features of the biodegradable NPs. 5-FU and MET NPs with chitosan as a biodegradable polymer were formulated by the ionotropic cross-linking method. 0.25 gm of MET and 0.25 gm of 5-FU were dissolved in 100 ml of distilled water, and stock solution was prepared. 5 ml of stock solution was slowly mixed into the chitosan solution to obtain the mixture of drugs and chitosan. The tripolyphosphate reserve liquid was dripped slowly into the chitosan solution with constant stirring until the opaline appearance was noticed in the mixture, then filtered, and dried. The NPs were evaluated for their physical properties and drug release kinetics. Cell proliferation assay was done using human colorectal carcinoma cell line (HCT 116).ResultsThe formulation composed of 1.5 w/v of chitosan, 0.25 w/v of MET, and 5-FU had an average particle diameter of 198.7 nm. The polydispersity index was 0.757. Thermal and infrared spectroscopy results indicated the drugs and polymers selected for the formulation were unique without any identifiable interaction. The NPs were spherical in appearance, with numerous pours on the surface, which was evident when microscopically examined. Uniformity in drug release was observed, and the formulation demonstrated excellent release kinetics. HTC 116 cell line confirmed that the maximum percentage of cell death and minimum viability of cells were observed while using the combination of MET and 5-FU-NPs as compared to the pure MET or 5-FU alone.ConclusionMET and 5-FU-loaded chitosan NPs were found to have excellent physiochemical properties, particle size, and drug release from the polymer in a controlled manner. Half-maximal inhibitory concentration value (IC50) of MET and 5-FU-NPs was found to be significantly less as compared to MET and 5-FU alone or the combination.

Application of Nanomaterials to Ensure Quality and Nutritional Safety of Food

Nanomaterials (NMs) are emerging novel tools for preserving quality, enhancing shelf life, and ensuring food safety. Owing to the distinctive physicochemical characters, engineered NMs under varying sizes and dimensions have great potentials for application in the manufacturing, packaging, processing, and safety of quality agrifood. The promise of various kinds of novel NMs that are useful for food industries has opened a possibility of a new revolution in agroprocessing industries in both the emerging and advanced nations. The rapid advancement of nanoscience has provided a great impact on material science that has allowed researchers to understand every aspect of molecular complexity and its functions in life sciences. The reduced size of NMs that increase the surface area is useful in the specific target of different organs, and biodegradable nanospheres are helpful in the transport of bioactive molecules across the cellular barriers. However, nanotechnology creates a great revolution in several sections including agriculture and food industry and also reduces environmental pollution, while the toxicity of some NMs in the food industry poses a great concern to researchers for their greater application. However, most of the developed countries have regulatory control acts but developing countries do not have them yet. Therefore, for the safe use of NMs and also to minimize the health and environmental risks in both the developed and developing countries, it is indispensable to recognize the toxicity-constructed, toxicodynamic, and toxicokinetic features of NMs, which should carefully be emphasized at the home and industrial levels. The current study highlights the updates of the NMs to safeguard the quality and nutritional safety of foods at home and also at the industrial level.

Nanospheres encapsulated everolimus delivery into arterial wall-the tissue pharmacokinetics and vascular response experimental study.

This study aimed to evaluate the pharmacokinetic profile and tissue effects of everolimus delivered into arterial wall using biodegradable nanospheres. Delivery of everolimus into the arterial wall is challenging due to its low-lipophilic profile. A pharmacokinetic study included 28 porcine coronary arterial segments initially injured with balloon angioplasty followed by the local delivery of everolimus encapsulated in nanospheres (EEN) via injection through a microporous delivery catheter. The animals were sacrificed at 1hour, 1,7,28, and 90-day follow-up. In the tissue effects study 16 coronary bare metal stent (BMS) were implanted following EEN delivery, 15 BMS following nanospheres delivery without the drug (reference group) and 16 implanted BMS served as a control. Angiographic and histology follow-up was scheduled at 28 and 90-day. The study showed high-everolimus concentrations in arterial tissue early after nanoparticles delivery followed by its gradual decrease to 1.15 ± 0.40 ng/mg at 90 days. Histology analysis showed favorable biocompatibility and healing profile with comparable area stenosis between groups at both time-points. The present study demonstrates for the first time the safety, biocompatibility, and long-term retention of everolimus in arterial tissue after single local delivery of biodegradable nanospheres.

BIODEGRADABLE NANOSPHERES - CURRENT STATUS

Nanospheres are polymeric matrix of spherical shape that ranges in size between 10- 200 nm in diameter. The drug is dissolved, entrapped, encapsulated or attached to the matrix of polymer. The nature of nanospheres can be amorphous or crystalline, and they potentiate to protect the drug from chemical and enzymatic degradation. In the matrix of this polymer, a drug will evenly distribute as well as physically and uniformly disperse and can enclose a variety of drugs, enzymes and, genes, providing a long circulation time. Nanospheres have the capability to convert poorly soluble, poorly absorbed and labile biologically active substance into promising deliverable drugs. This review focuses on the mechanism for synthesis of nano-based drug delivery systems, characterization, and application of biodegradable nanospheres and mainly on successful formulations based on biodegradable nanospheres.

Nanofibrous spongy microspheres to deliver rabbit mesenchymal stem cells and anti-miR-199a to regenerate nucleus pulposus and prevent calcification

Lower back pain is mainly caused by intervertebral disc degeneration, in which calcification is frequently involved. Here novel nanofibrous spongy microspheres (NF-SMS) are used to carry rabbit bone marrow mesenchymal stromal cells (MSCs) to regenerate nucleus pulposus tissues. NF-SMS are shown to significantly enhance the MSC seeding, proliferation and differentiation over control microcarriers. Furthermore, a hyperbranched polymer (HP) with negligible cytotoxicity and high microRNA (miRNAs) binding affinity is synthesized. The HP can complex with anti-miR-199a and self-assemble into “double shell” polyplexes which are able to achieve high transfection efficiency into MSCs. A double-emulsion technique is used to encapsulate these polyplexes in biodegradable nanospheres (NS) to enable sustained anti-miR-199 delivery. Our results demonstrate that MSC/HP-anti-miR-199a/NS/NF-SMS constructs can promote the nucleus pulposus (NP) phenotype and resist calcification in vitro and in a subcutaneous environment. Furthermore, injection of MSC/HP-anti-miR-199a/NS/NF-SMS can stay in place, produce functional extracellular matrix, maintain disc height and prevent intervertebral disc (IVD) calcification in a rabbit lumbar degeneration model.

In natura and nanoencapsulated essential oils from Xylopia aromatica reduce oviposition of Bemisia tabaci in Phaseolus vulgaris

Bemisia tabaci is an agricultural pest of worldwide distribution that causes serious damage to several crops. It is of crucial importance to control this pest, especially for large-scale production. Accordingly, formulations based on essential oils of pesticidal action are potentially promising in the agricultural sector. Additionally, the nanoencapsulation of these bioactive compounds promotes their protection from environmental degradation and prolongs their biological activity. Here, we develop PCL (poly-e-caprolactone) nanoparticles containing essential oils of Xylopia aromatica leaves and fruits and evaluate their insecticidal effect in B. tabaci Middle East Asia Minor 1 biotype B. The average yields of essential oils from leaves and fruits of X. aromatica were 0.05 and 0.80%, respectively. The major compounds in the essential oil of leaves were bicyclogermacrene (44.80%), α-pinene (8.23%) and β-pinene (7.75%) while in fruits were α-pinene (35.40%), β-phellandrene (31.05%) and β-pinene (22.51%). The PCL nanoparticles containing the essential oils exhibited encapsulation efficiency of 95% and particle diameter smaller than 500 nm. Biodegradable nanospheres substantially protected the essential oils from accelerated degradation caused by UV light and also prevented possible phytotoxic activity of the in natura essential oil from leaves of X. aromatica in high concentrations, probably due to the gradual release. In natura and nanoencapsulated essential oils from leaves and fruits decreased (up to 98%) the oviposition of B. tabaci in common bean leaves. Our results indicate that both in natura and nanoencapsulated oils of X. aromatica may potentially be used as alternative to the chemical control of B. tabaci.

Injectable nanofibrous spongy microspheres for NR4A1 plasmid DNA transfection to reverse fibrotic degeneration and support disc regeneration.

Safe and efficient gene therapy is highly desired for controlling pathogenic fibrosis of nucleus pulposus (NP) tissue, which would result in intervertebral disc (IVD) degeneration and disability if left untreated. In this work, a hyperbranched polymer (HP) with high plasmid DNA (pDNA) binding affinity and negligible cytotoxicity is synthesized, which can self-assemble into nano-sized polyplexes with a "double shell" structure that can transfect pDNA into NP cells with very high efficiency. These polyplexes are then encapsulated in biodegradable nanospheres (NS) to enable two-stage delivery: 1) temporally-controlled release of pDNA-carrying polyplexes and 2) highly efficient delivery of pDNA into cells by the released polyplexes. These biodegradable NS are co-injected with nanofibrous spongy microspheres (NF-SMS) to localize the cellular transfection of the pDNA encoding orphan nuclear receptor 4A1 (NR4A1), which was recently reported as a therapeutic agent to delay pathogenic fibrosis. It is shown that HP can transfect human NP cells efficiently invitro with low cytotoxicity. The two-stage delivery system is able to present the polyplexes over a sustained time period (more than 30 days) in the tail of a rat. The NR4A1 pDNA carried by the HP polyplexes is found to therapeutically reduce the pathogenic fibrosis of NP tissue in a rat-tail degeneration model. In conclusion, the combination of the two-stage NR4A1 pDNA delivery NS and NF-SMS is able to repress fibrosis and to support IVD regeneration.

Abstract IA18: Targeted polymeric nanoparticles: From academic innovations to clinical trials and lessons learned

Abstract A variety of organic and inorganic materials have been utilized to generate nanoparticles for drug delivery applications, including polymeric nanoparticles, dendrimers, nanoshells, liposomes, nucleic acid based nanoparticles, magnetic nanoparticles, and virus nanoparticles. The two most commonly used systems are polymeric nanoparticles and liposomes [1, 2]. Controlled release polymer technology has impacted virtually every branch of medicine, including ophthalmology, pulmonary, pain medicine, endocrinology, cardiology, orthopedics, immunology, neurology and dentistry, with several of these systems in clinical practice today such as Atridox, Lupron Depot, Gliadel, Zoladex, Trelstart Depot, Risperidol Consta and Sandostatin LAR. The annual worldwide market of controlled release polymer systems which extends beyond drug delivery is now estimated at $100 billion and these systems are used by over 100 million people each year. Polymeric nanoparticles can deliver drugs in the optimum dosage over time, thus increasing the efficacy of the drug, maximizing patient compliance and enhancing the ability to use highly toxic, poorly soluble, or relatively unstable drugs. These systems can also be used to co-deliver two or more drugs for combination therapy [3]. The surface engineering of these nanoparticles may yield them “stealth” to prolong their residence in blood [4] and the functionalization of these particles with targeting ligands can differentially target their delivery or uptake by a subset of cells [5], further increasing their specificity and efficacy [6]. The successful clinical translation of therapeutic nanoparticles requires optimization of many distinct parameters including: variation in the composition of the carrier system, drug loading efficiency, surface hydrophilicity, surface charge, particle size, density of possible ligands for targeting, etc., resulting in a large number of potential variables for optimization which is impractical to achieve using a low throughput approach. More recently combinatorial approaches have been developed to precisely engineer nanoparticles and screen multiple nanoparticle characteristics simultaneously with the goal of identifying formulations with the desired physical and biochemical properties for each specific application [7]. The goal of this talk is to review our efforts in the design and optimization of polymeric nanoparticles for medical applications, which formed the foundation for the clinical translation of the first-in-human targeted and controlled-release nanoparticles, BIND-014 and SEL-068 [8, 9].

Systems of local drug delivery to arterial wall for prevention of in-stent restenosis

New generation, drug-eluting stents used in the treatment of coronary and peripheral atherosclerotic disease (CPAD) significantly reduced restenosis and revascularization rates as well as frequency of thrombosis as compared to bare metal stents and first-generation drug eluting stents. However, despite fast development of this technology several reports have been published recently that describe cases of late and very late stent thrombosis, restenosis and neoatheroslerosis within arterial segments with previously implanted stents. For this reason many research are being conducted with the aim to design alternative methods for intra-arterial drugs delivery in order to reduce restenosis and revascularization rates, yet eliminating adverse effects mentioned above. One of possibilities is lipophilic and antiproliferative drug coated balloon technology, which offers high drug concentration in arterial tissue and restenotic effect in selected clinical situations despite the short balloon inflation time. A particularly interesting option is intra-arterial delivery of drugs with different mechanisms of action, regardless of their lipophilicity by loading them into biodegradable nanospheres. In this paper, currently used systems for local drug delivery have been described including their limitations and opportunities. In addition, we provided a brief description of the project sponsored by Polpharma Scientific Foundation, which aimed to evaluate potentials of local delivery of biodegradable nanospheres loaded with everolimus, which could be used to reduce restenosis rate after stent implantation.

Literature review on Biodegradable Nanospheres for Oral and Targeted Drug Delivery

Nanosphere systems have great potentials, being able to convert poorly soluble, poorly absorbed and labile biologically active substance into promising deliverable drugs. The core of this system can enclose a variety of drugs, enzymes, genes and is characterized by a long circulation time due to the hydrophilic shell which prevents recognition by the reticular-endothelial system. To optimize this drug delivery system, greater understanding of the different mechanisms of biological interactions, and particle engineering, is still required. Further advances are needed in order to turn the concept of nanoparticles technology into a realistic practical application as the next generation of drug delivery system.

Enhanced Hippocampal Neurogenesis in APP/Ps1 Mouse Model of Alzheimer’s Disease After Implantation of VEGF-loaded PLGA Nanospheres

During adult life, hippocampus is an important brain region involved in neurogenesis. The generation and cell death of newly generated neuronal cells in this region have critical roles in brain maintenance and alterations in these processes are seen in Alzheimer's disease (AD). For the purpose of carrying out a neuroregenerative strategy, we propose a novel approach based on the encapsulation of vascular endothelial growth factor (VEGF) in poly (lactic co-glycolic acid) (PLGA) biodegradable nanospheres (NS) administered by craniotomy to stimulate the proliferation of neuronal precursors in a transgenic mouse model of AD. VEGF loaded nanospheres were prepared by double emulsion solvent evaporation technique, obtaining 200 nm nanospheres with a biphasic release profile. After demonstrating their efficacy in the proliferation and differentiation of neuronal cell cultures, in vivo studies were carried out. 3 months after VEGF-NS were implanted directly into the cerebral cortex of APP/Ps1 mice, the determination of BrdU(+) cells in the whole hippocampal region and specifically in the dentate gyrus, demonstrated a significantly enhanced cellular proliferation in VEGF-NS treated group. These results were also confirmed showing an increased number of DCX(+) and NeuN(+) cells. Hence, PLGA-VEGF nanospheres may be a potential strategy to modulate proliferative neuronal progenitors in the hippocampal region, and therefore, provide new insight for future therapeutic approaches in AD.

Coated biodegradable casein nanospheres: a valuable tool for oral drug delivery

Biodegradable casein nanospheres for the sustained release of bioactive molecules in the gastro-intestinal tract were prepared by precipitation polymerization using sodium methacrylate (NaMA) and N,N′-methylene bis-acrylamide (MEBA) as pH-responsive monomer and cross-linker. Three materials with different casein amount were obtained and characterized by scanning electron microscopy, dimensional analysis, water uptake, cytotoxicity and enzymatic degradation experiments. Nanospheres biodegradability was tuned by coating with polyacrylic acid. Coated and uncoated materials were investigated as delivery vehicles for diclofenac sodium salt. For un-coated samples, the release raise 100% in 30 h, while for coated specimens these values were lower than 70%, due to the diffusional constraints of polymer layer.

Insecticidal effect of nanoencapsulated essential oils from Zanthoxylum rhoifolium (Rutaceae) in Bemisia tabaci populations

The purpose of this study was to develop and characterize biodegradable nanospheres containing essential oils from Zanthoxylum rhoifolium leaves and evaluate its insecticidal effect in Bemisia tabaci populations. The essential oil from Z. rhoifolium leaves exhibited an average yield of 0.03% and presented β-elemene (31.26%), D-germacrene (18.16%), β-caryophyllene (12.09%), δ-elemene (7.63%), β-cedrene (6.69%), bicyclogermacrene (4.57%) and E-caryophyllene (3.63%) as main components. The PCL nanospheres containing this essential oil exhibited encapsulation efficiency higher than 96%, pH close to 5, particle diameter smaller than 500nm and zeta potential values of approximately −20mV. The in vitro release profile was characteristic of biphasic release, i.e., a fast initial release, followed by slow release for 12h or more. The biological assay results were also significant and as such both the in natura and nanoencapsulated essential oils resulted in reductions as high as 95% in the number of eggs and nymphs compared with our control. Collectively these results suggest that both in natura and nanoencapsulated essential oils from Z. rhoifolium leaves can potentially be used in B. tabaci control in association with integrated pest management practices.

VEGF-releasing biodegradable nanospheres administered by craniotomy: A novel therapeutic approach in the APP/Ps1 mouse model of Alzheimer's disease

This study attempts to develop a novel nanotechnology-based strategy to deliver vascular endothelial growth factor (VEGF) to the brain, as a possible therapeutic approach for AD. For this purpose, VEGF was encapsulated in biodegradable poly(lactic-co-glycolic acid) (PLGA) nanospheres (VEGF-NS). The nanosphere particle size was about 200nm, with a narrow size distribution, and the zeta potential around −30mV. The encapsulation efficiency of VEGF was 44.06±5.61%, showing a biphasic release profile in vitro. The biological activity and neuroprotective effect of encapsulated VEGF were investigated in neuronal cell cultures, confirming the neuronal proliferative effect and the protection against Aβ42 induced neurotoxicity. In vivo studies were carried out in amyloid precursor protein/presenilin-1 (APP/Ps1) mice administering VEGF-NS through minimally invasive craniotomy. The results obtained showed that VEGF-NS were able to improve behavioral deficits, decrease Aβ deposits and promote angiogenesis, as well as reduce neuronal loss and cerebrovascular abnormalities. Furthermore, their ability to protect neuronal cultures against neuroinflammation induced by LPS provides new insight for future therapeutic approaches in other neurodegenerative disorders.

Preparation and characterisation of 5-fluorouracil containing PLGA nanospheres coated with chitosan, for drug delivery

The aim of this study was to design a new Drug Delivery System (DDS) based on poly (lactide–co–glycolide) (PLGA) biodegradable nanospheres (NS) coated with Chitosan (CTS), in order to prolong its residence time and to deliver the nanoparticles more specifically to cancer cells. We have tried three methods of incorporation of Chitosan in the nanoparticles, but only one was efficient. The first method is named entanglement of chains, the second method is known as single adsorption and, in the third, we prior linked covalently Chitosan to the polymer and then prepared the nanoparticles. After selected the best method, it was monitored the stability following the temporal variation of diameter, polydispersity and zeta potential of particles prepared using different percentages of CTS and pH values, using a pre–optimised formulation of 5–fluorouracil containing PLGA NS.

Preparation of Biodegradable Gelatin Nanospheres with a Narrow Size Distribution for Carrier of Cellular Internalization of Plasmid DNA

The objective of this study is to design biodegradable nanospheres of cationized gelatin as a carrier of cellular internalization of plasmid DNA. Ethylenediamine was chemically introduced into the carboxyl groups of gelatin to obtain cationized gelatin. The gelatin solution was filtered through a glass membrane under high pressure and dropped into 2-butanol, acetone or a mixture of the two to form nanospheres of cationized gelatin. The microspheres of cationized gelatin were prepared by the conventional water-in-oil emulsion method. The resulting nano- and microspheres of cationized gelatin were dehydrothermally treated at 160°C for different time periods to allow them to cross-link chemically. The size of nanospheres, prepared by the filtration method and changed by the type of solvents, was 1.86, 0.83 or 0.24 μm. The in vitro degradation of spheres became faster as the time period of dehydrothermal treatment was shorter. The degradation time of spheres in HCl solution linearly increased with an increase in the cross-linking time, irrespective of the sphere size. However, in the collagenase solution, when compared at the similar cross-linking density, the smaller spheres were degraded more slowly than the larger ones. The plasmid DNA incorporated in the nanospheres was released from the nanospheres with their degradation. The nanospheres incorporating plasmid DNA were internalized into cells, and intracellularly degraded with time to release plasmid DNA. The time period of plasmid DNA release was prolonged by increasing the nanosphere degradation time.

Biodegradable nanospheres self-assembled from complementary hydrophilic dextran macromers

Supramolecular self-assemblies are predominately driven by noncovalent molecular forces, and electrostatic interactions are the major force for charged molecules. In this paper, we demonstrate the self-assembly of hollow nanospheres from oppositely charged dextran-based hydrophilic macromers. Charged dextran derivatives were obtained by incorporating 2-bromoethylamine (Dex–BH) and chloroacetic acid (Dex–CA) into dextran. In a pH 5.0 buffer solution, Dex–BH and Dex–CA became protonated and deprotonated, respectively, and self-assembled into well-defined nanospheres. Dynamic light scattering (DLS) detected that these nanospheres have a uniform size distribution with a mean diameter of approximately 160nm, but their size and distribution are largely dependent on molecular weight and pH value. Scanning electron microscopy (SEM) analysis revealed that these nanospheres could form a hollow architecture, which might be attributed to the hydrophilic characteristics of dextran macromers. An in vitro albumin release study indicates that the release rate reflects the nanosphere architecture, and further demonstrates their potential as drug delivery vehicles.

A Versatile Biodegradable Polymer with a Thermo-Reversible/Irreversible Transition

A versatile biodegradable thermoresponsive polymer was developed. The polymer has succinimide and isopropylasparamide segments and exhibits a phase transition with thermoreversibility that can be controlled by changing the polymer composition. With fewer succinimide units, the polymer exhibits the type of thermo-reversible phase transition that is characteristic of poly(N-isopropylacrylamide) (PNIPAAm). The polymer with a higher proportion of succinimide units exhibits a thermo-irreversible phase transition, resulting in the formation of nanospheres that are stable below the transition temperature. The stable nanospheres are generated by dehydration and subsequent conformational stabilization through an interaction between imide rings. This thermoirreversible phase transition in water provides a simple, oil-free preparation of biodegradable nanospheres.

Nanospheres formulated from l-tyrosine polyphosphate as a potential intracellular delivery device

Current delivery devices for drugs and genes such as films and microspheres are usually formulated from polymers that degrade over a period of months. In general, these delivery systems are designed to achieve an extracellular release of their encapsulated drugs. For drugs that require interaction with cellular machinery, the efficacies of both macroscopic and microscopic delivery systems are normally low. In contrast, nano-sized drug delivery vehicles could achieve high delivery efficiencies, but they must degrade quickly, and the delivery system itself should be nontoxic to cells. In this aspect, biodegradable nanospheres formulated from l-tyrosine polyphosphate (LTP) have been produced from an emulsion of oil and water for the potential use as an intracellular delivery device. Scanning electron microscopy (SEM) and dynamic laser light scattering (DLS) show that LTP nanospheres possess a diameter range between 100 and 600nm. SEM reveals nanospheres formulated from LTP are spherical and smooth. Additionally, DLS studies demonstrate that nanospheres degrade hydrolytically in 7 days. Confocal microscopy reveals LTP nanospheres are internalized within human fibroblasts. Finally, the cell viability after exposure to LTP nanospheres and determined with a LIVE/DEAD® Cell Viability Assay is comparable to a buffer control. In conclusion, our nanospheres have been shown to be nontoxic to human cells, possess the appropriate size for endocytosis by human cells, and degrade within 7 days. Therefore LTP nanospheres can be used for a sustained intracellular delivery device.

A detailed analysis of biodegradable nanospheres by different techniques—A combined approach to detect particle sizes and size distributions

Poly( d, l-lactide-co-glycolide) nanosupensions as intravenous nanosphere systems were produced by solvent deposition in aqueous Poloxamer 188 solutions. Light scattering techniques were applied to these colloidal systems to characterize particle sizes. Regularly shaped spherical particles were received as proved by freeze fracture replica and small-angle X-ray scattering (SAXS). SAXS was performed using intensive synchrotron radiation. Particle sizes were calculated from the small-angle part of scattering curve that were in good agreement with z-average values received from photon correlation spectroscopy (PCS). The flow field-flow fractionation (FlFFF) fractograms in combination with multi-angle light scattering (MALS) allowed an easy detection of maximum particle sizes what is most important for parenteral systems. Furthermore, high quality size distributions were received due to the separation step prior to size characterization. The calculated average size values exhibited a good correlation with z-averages determined by PCS. Only for suspensions of broader size distributions, higher deviations were observed. Comparing particle sizes with and without Poloxamer, differences in diameters resulted that were quantified. The additional Poloxamer shell was not able to be removed by an intensive washing during FlFFF focusing and separation. Especially FlFFF/MALS proved to be a valuable tool to characterize the pharmaceutical nanosuspensions in detail what is of great importance especially for controlled drug delivery systems.