Insight into the mechanisms of combined toxicity of cadmium and flotation agents in luminescent bacteria: Role of micro/nano particles.

Currently, risk assessment and pollution management in mines primarily focus on toxic metals, with the flotation agents being overlooked. However, the combined effects of metals and flotation agents in mines remain largely unknown. Therefore, this study aimed to evaluate the combined effects of Cd and two organic flotation agents (ethyl xanthate (EX) and diethyldithiocarbamate (DDTC)), and the associated mechanisms. The results showed that Cd + EX and Cd + DDTC exhibited synergistic toxicity. The EC50 values for luminescent bacteria were 1.6 mg/L and 1.0 mg/L at toxicity unit ratios of 0.3 and 1, respectively. The synergistic effects were closely related with the formation of Cd(EX)2 and Cd(DDTC)2 micro/nano particles, with nano-particles exhibiting higher toxicity. We observed severe cell membrane damage and cell shrinkage of the luminescent bacteria, which were probably caused by secondary harm to cells through the released CS2 during their decomposition inside cells. In addition, these particles induced toxicity by altering cellular levels of biochemical markers and the transcriptional levels of transport proteins and lipoproteins, leading to cell membrane impairment and DNA damage. This study has demonstrated that particulates formed by Cd and flotation agents contribute to the majority of the toxicity of the binary mixture. This study helps to better understand the complex ecological risk of inorganic metals and organic flotation agents in realistic mining environments.

Toxic effects of nSiO2 and mPS on diatoms Nitzschia closterium f. minutissima.

To investigate the toxic mechanism of SiO2 nanoparticles (nSiO2) and polystyrene microplastics (mPS) on microalgae Nitzschia closterium f. minutissima, growth inhibition tests were carried out. The growth and biological responses of the algae exposed to nSiO2 (0.5, 1, 2, 5, 10, 30 mg L-1) and mPS (1, 5, 10, 30 and 75 mg L-1) were explored in f/2 media for 96 h. Both micro-/nano-particles (MNPs) inhibited the growth of N. closterium f. minutissima in a concentration- and time-dependent manner. The toxic effect of mPS on N. closterium f. minutissima is higher than that of nSiO2, because silicon is essential for diatoms to maintain cell wall integrity, and the addition of appropriate amounts of nSiO2 can be absorbed and used as a nutrient to promote diatom growth and protect the integrity of the siliceous shell to some extent. Both MNPs induce the production of excess oxidation and activate the cellular antioxidant defense system, leading to increased SOD and CAT activity as a means to resist oxidative damage to the cell, and eliminating excess ROS and maintaining normal cell morphology and metabolism. SEM is consistent with the results of MDA, showing that mPS with high concentrations attach to the surface of algal cells to produce heterogeneous aggregates and disrupt the cell wall and cell membrane, causing the cells to expand and rupture. This study contributes to the understanding of the size effect of MNPs on the growth of marine diatom.

Flavor mechanism of micro-nanoparticles and correlation analysis between flavor substances in thermoultrasonic treated fishbone soup.

To study the physicochemical properties of micro-nanoparticles (MNPs) in thermoultrasonic treated fishbone soup, it was subjected to ultra-filtration with a 100 kDa ultrafiltration membrane to obtain large MNPs (LMNPs) and small MNPs (SMNPs). LMNPs and SMNPs were treated with force-breakers, and the interactions of the MNPs with five characteristic volatile compounds were investigated. LMNPs covered most proteins (222.66 mg/mL) and fatty acids (363.76 mg/g), while SMNPs was mostly soluble small molecules with taste substances like total free amino acids (85.26 mg/g), organic acids (2.55 mg/mL), and 5'-nucleotides (169.17 mg/100 mL). The stability of LMNPs is significantly higher than raw bone soup, and SMNPs can exist stably in the solution. Correlation analysis between flavor substance content and flavor suggested that the overall flavor profile of halibut bone soup was closely related to the content changes of 72 significant influence variables. The binding of LMNPs to characteristic flavor compounds was largely affected by hydrophobic interactions, hydrogen bonds, and ionic effects. While the binding of SMNPs to characteristic flavor compounds was largely determined by hydrophobic interaction and hydrogen bonding. This study explores the characteristics of MNPs and provides the possibility to clarify the interaction mechanism between MNPs and flavor.

Accumulation and ecotoxicological effects induced by combined exposure of different sized polyethylene microplastics and oxytetracycline in zebrafish.

Microplastics have been widely reported as carriers of antibiotics, yet studies investigating the combined ecotoxicology of microplastics and antibiotics on organisms is limited. In this study, different sized polystyrene plastics and oxytetracycline (OTC) were used to carry out a 30-day single and binary-combined exposure experiment of zebrafish, and the microplastics and OTC accumulation, liver histological alteration, biomarkers and transcriptomic response of zebrafish were evaluated. Our results indicated that 300 nm and 50 nm plastic particles increased the OTC accumulation in liver by 33.8% and 44.5%, respectively. Microplastics and OTC induced severe liver histological damage, and the damage is size-dependent, increasing with the decrease of microplastics sizes. The liver biomarkers indicated a different response pattern in single microplastics exposure and combined with OTC, single or co-exposure of 50 nm nano-plastics and OTC induced intense responses of integrated biomarker response values. The 50 nm nano-plastics, OTC and their combined exposure induced 1330, 2693 and 3965 significantly differentially expressed genes, respectively, in which the steroid biosynthesis pathway was significantly affected by all the three treatments. This study elucidated the size-dependent effects of microplastics and provided detailed data from histopathology to transcriptome profile, enhancing our understanding of the ecotoxicity of microplastics and OTC.

Is hydrodynamic diameter the decisive factor? - Comparison of the toxic mechanism of nSiO2 and mPS on marine microalgae Heterosigma akashiwo.

To investigate the toxic mechanism of SiO2 nanoparticles (nSiO2) and polystyrene microplastics (mPS) on microalgae Heterosigma akashiwo, growth inhibition tests were carried out. The growth and biological responses of the algae exposed to nSiO2 (0.5, 1, 1.5, 2, 5, 10 and 30 mg L-1) and mPS (1, 2, 5, 10, 30 and 75 mg L-1) were explored in f/2 media for 96 h. It was found that the hydrodynamic diameter of the particles seems to be one of the more important factors to influence the algae. nSiO2 and mPS with similar hydrodynamic diameters have the similar toxic mechanism on H. akashiwo, and the effects were dose- and time-dependent. High concentrations of micro-/nano-particles (MNPs) could inhibit the growth of algal cells, however, low concentrations of MNPs did not restrict or even promoted the growth of algae, known as "Hormesis" phenomenon. The 96 h-EC20 values of nSiO2 and mPS on H. akashiwo were 2.69 and 10.07 mg L-1, respectively, and chlorophyll fluorescence parameters indicated that the microalgal photosynthetic system were inhibited. The hydrophilic surface of nSiO2 increased the likelihood of nSiO2 binding to the hydrophilic functional group of microalgae, which may account for the slightly stronger toxic effect of nSiO2 than mPS. The algae continued to produce reactive oxygen species (ROS) under stress conditions. Total protein (TP) levels reduced, and superoxide dismutase (SOD) and catalase (CAT) levels increased to maintain ROS levels in the cells. The decrease in adenosine triphosphate (ATPase) indicated an impact on cellular energy metabolism. Cell membrane damage, cytoplasm and organelle efflux under stress were confirmed by scanning and transmission electron microscopy (SEM and TEM) images. This study contributes to the understanding of the size effect of MNPs on the growth of marine microalgae.

Combined effects of micro-/nano-plastics and oxytetracycline on the intestinal histopathology and microbiome in zebrafish (Danio rerio).

Accumulated evidence has demonstrated that microplastics and oxytetracycline (OTC) affect organisms, but few studies have investigated their combined effects on aquatic organisms. In this study, adult zebrafish (Danio rerio) were exposed to single and binary-combined contamination of micro-, nano-sized polystyrene plastics and OTC for 30 days, and the intestinal histopathology, gut microbiota and antibiotic resistance genes (ARGs) of zebrafish were measured. The results showed that the intestinal epithelial damage increase with the decrease of plastic sizes. Nano-sized plastics, OTC and their combined exposure caused intestinal epithelial damage, and co-exposure with micro-sized plastics reduced the intestinal damage caused by single OTC exposure. The gut microbial communities were affected by the combined exposure to microplastics and OTC. Compared with the blank control, the relative abundance of Fusobacteria increased 12.7 % and 21.1 % in OTC combined with 45-85 µm micro-plastics (MOTC) and 40-54 nm nano-plastics (NOTC), respectively, and that of Bacteroidetes increased 26.2 % and 18.6 % in the MOTC and NOTC treatments, respectively. The effects of MOTC and NOTC on the biodiversity of the zebrafish gut microbiome were different; MOTC increased the biodiversity by 11.3 % compared with the blank control, whereas NOTC decreased the biodiversity by 8.8 % compared with the blank control. Furthermore, the abundance of ARGs in 40-54 nm nano-plastics, MOTC and NOTC treatments was increased 96.9 %, 96.6 % and 68.8 % compared with the control group, respectively. Additionally, significant differences were observed in ARGs characteristics between the micro- and nano-plastics treated groups whether combined with OTC or not. These results are essential to further understand the combined ecotoxicological effects of micro- or nano-plastics and antibiotics on aquatic organisms.

Corrigendum: Micro-Nano Bioactive Glass Particles Incorporated Porous Scaffold for Promoting Osteogenesis and Angiogenesis in vitro.

[This corrects the article DOI: 10.3389/fchem.2019.00186.].

Formation of colloidal micro-nano particles and flavor characteristics of Greenland halibut bone soup.

In this study, halibut bone, a byproduct of Greenland halibut processing, was prepared into a thick soup through a non-frying process. The formation of colloidal micro-nano particles and flavor characteristics in halibut bone soup was explored. The results showed that the nutrients in halibut bones migrated to the soup continuously with the cooking process and reached the highest concentration (total sugars, 38.16 mg/100 ml; water-soluble proteins, 25.71 mg/ml; fatty acids, 2.15 g/100 ml; solids, 1.14 g/100 ml) at 150 min. Taste substances such as organic acids, 5'-nucleotides and total free amino acids (TFAAs) content in halibut bone soup also reached maximum at 150 min. At this time, results for particle size showed that MNPs with uniform size (725.62 nm) were formed, which made the bone soup milky white, stable, and had good tasting. Headspace-gas chromatography-ion mobility spectrometry results showed that a total of 59 volatile substances were detected from the halibut bone soup. The content of volatile flavor substances in the 150 min group was lower than that in the 90-120 min group. Meanwhile, aldehydes and ketones gradually became esters. PRACTICAL APPLICATION: Soup is an indispensable part of the world food culture. In order to increase the added value of Greenland halibut, halibut bone soup was studied in this paper. This study found that halibut bone soup that had not been fried, formed the MNPs and has a more harmonious and pleasant flavor. Thus, non-fried halibut bone soup is a good processing method and can improve economic efficiency.

Effects of thermoultrasonic treatment on characteristics of micro-nano particles and flavor in Greenland halibut bone soup.

In order to investigate the effects of thermoultrasonic treatment (TUT) on the formation of colloidal micro-nano particles (MNPs) and the quality of halibut bone soup, nutrients, particle characteristics, and flavor characteristics were analyzed. The morphology of MNPs was studied using an optical microscope. Results showed that TUT could increase the nutrient content (total sugars, 22.15 mg/100 mL; water soluble proteins, 173.24 mg/mL; fatty acids, 1779.7 mg/100 mL; solids, 3.16 g/100 mL), reduce the particle size (605.92 nm) and interfacial tension. Meanwhile, TUT make the halibut bone soup has better emulsifying characteristics and stability. The contents of flavor substances, such as esters, 5'-nucleotides, organic acids in the halibut bone soup were more abundant, while the contents of hexanal and 1-octen-3-ol and fishy off-flavor were reduced in TUT group. The overall odor and taste outline were more harmonious. Therefore, TUT can be used in the production of high quality fish bone soup, and TUT could be considered as a good deep processing technology for halibut bone and improve economic efficiency.

Electrohydrodynamic atomisation driven design and engineering of opportunistic particulate systems for applications in drug delivery, therapeutics and pharmaceutics.

Electrohydrodynamic atomisation (EHDA) technologies have evolved significantly over the past decade; branching into several established and emerging healthcare remits through timely advances in the engineering sciences and tailored conceptual process designs. More specifically for pharmaceutical and drug delivery spheres, electrospraying (ES) has presented itself as a high value technique enabling a plethora of different particulate structures. However, when coupled with novel formulations (e.g. co-flows) and innovative device aspects (e.g., materials and dimensions), core characteristics of particulates are manipulated and engineered specifically to deliver an application driven need, which is currently lacking, ranging from imaging and targeted delivery to controlled release and sensing. This demonstrates the holistic nature of these emerging technologies; which is often overlooked. Parametric driven control during particle engineering via the ES method yields opportunistic properties when compared to conventional methods, albeit at ambient conditions (e.g., temperature and pressure), making this extremely valuable for sensitive biologics and molecules of interest. Furthermore, several processing (e.g., flow rate, applied voltage and working distance) and solution (e.g., polymer concentration, electrical conductivity and surface tension) parameters impact ES modes and greatly influence the production of resulting particles. The formation of a steady cone-jet and subsequent atomisation during ES fabricates particles demonstrating monodispersity (or near monodispersed), narrow particle size distributions and smooth or textured morphologies; all of which are successfully incorporated in a one-step process. By following a controlled ES regime, tailored particles with various intricate structures (hollow microspheres, nanocups, Janus and cell-mimicking nanoparticles) can also be engineered through process head modifications central to the ES technique (single-needle spraying, coaxial, multi-needle and needleless approaches). Thus, intricate formulation design, set-up and combinatorial engineering of the EHDA process delivers particulate structures with a multitude of applications in tissue engineering, theranostics, bioresponsive systems as well as drug dosage forms for specific delivery to diseased or target tissues. This advanced technology has great potential to be implemented commercially, particularly on the industrial scale for several unmet pharmaceutical and medical challenges and needs. This review focuses on key seminal developments, ending with future perspectives addressing obstacles that need to be addressed for future advancement.

Micro-nano particle formation and transformation mechanisms of broth in meat braised processing.

The formation and transformation mechanisms of micro-nano particles (MNPs) in broth during meat braising were systematically investigated through a sophisticated controlled process. Dynamic changes in the morphology, composition and spatial distribution of MNPs were comprehensively characterized, and subsequently the mechanisms were visually uncovered from microcosmic-spatial perspectives. MNPs formed as circular-shape colloidal systems with an aggrandizing tendency for particle number and size and gradually stabilize eventually. Specifically, the major MNPs gradually increased the size from <400 nm to ~1500 nm and accumulated triglycerides and glycoconjugates resulting from lipid oxidation, Maillard reaction, etc. Continuous formation of MNPs in broth progressively facilitated the spatial coalescence and self-assembly of free substances driven by intermolecular interactions, and consequently principal nutrients and flavor compounds further accumulated in the MNPs by the braising process. Hence, this work not only revealed the MNP formation and transformation mechanisms but offered a foundation for investigating MNP-dependent effect on broth flavor.

Micro-interaction of mucin tear film interface with particles: The inconsistency of pharmacodynamics and precorneal retention of ion-exchange, functionalized, Mt-embedded nano- and microparticles.

Physiological reflexes and anatomical barriers render traditional eye drop delivery inefficient. We previously reported that drug-loaded nanoparticles and microspheres prepared from montmorillonite and Eudragit polymers exhibited good sustained-release and lowered intraocular pressure. Here, we compared the performance of optimized formulations to select the most suitable formulation for glaucoma therapy. We found that the microspheres had much higher encapsulation efficiency and drug loading than nanoparticles. Moreover, cytocompatibility experiments demonstrated that nanoparticles showed more severe cytotoxicity than microspheres, probably due to their smaller particles, enhanced cell uptake, and intracellular solubility. Interestingly, the pre-corneal retention time of nanoparticles reflected a clear advantage over microspheres, while the duration of the pharmacological effect of nanoparticles was not as good as that of microspheres: compared with the nanoparticle depressurization duration of only 8 h, the microspheres continuously depressurized for 12 h. The slower release of the microspheres and its micro-interaction mechanism with the discontinuous mucin layer of the tear film led to the inconsistency between duration of pharmacodynamics and fluorescence ocular retention time. In summary, the lower cytotoxicity and longer pharmacological effect of microspheres indicate their potential advantages for glaucoma applications.

Pickering emulsions stabilized by luteolin micro-nano particles to improve the oxidative stability of pine nut oil.

BACKGROUND: Pine oil contains a high percentage of polyunsaturated fatty acids, which make it prone to oxidation. Luteolin (LUT) micro-nano particles with antioxidant properties can be used as stabilizers to form an edible oil-in-water Pickering emulsion to improve the oxidative stability of pine nut oil. RESULTS: Under optimal preparation conditions, the LUT micro-nano particles and pine nut oil account for about 0.44 and 90.9 g·kg-1 of the total mass of the emulsion, respectively. The LUT particles in the suspension have a mean particle size of about 479 nm, present a sheet-like structure with a cut surface of 30-50 nm, and can reduce the surface tension of deionized water. In the optimized Pickering emulsion, the emulsion droplets are approximately spherical and have a mean diameter of about 125.6 nm and uniform distribution. The optimized Pickering emulsion droplets can remain stable for up to 2 h in an environment where the pH levels are 7-8.5, ultraviolet B radiation (UVB) irradiation, of less than 5.0 g·kg-1 , and at a temperature of 80 °C. The stability of the emulsion in simulated digestive fluid changed minimally. In the first 7 days of the accelerated oxidation experiment, LUT micro-nano particles not only successfully protected the integrity of emulsion droplets but also fully inhibited the peroxidation of pine oil. CONCLUSION: The strong antioxidant properties of LUT micro-nano particles, and the dense protective layer they formed, stabilized the Pickering emulsion successfully. The particles also improved the oxidation stability of pine nut oil. © 2020 Society of Chemical Industry.

Microfluidic Chip based direct triple antibody immunoassay for monitoring patient comparative response to leukemia treatment.

We report a time and cost-efficient microfluidic chip for screening the leukemia cells having three specific antigens. In this method, the target blast cells are double sorted with immunomagnetic beads and captured by the 3rd antibody immobilized on the gold surface in a microfluidic chip. The captured blast cells in the chip were imaged using a bright-field optical microscope and images were analyzed to quantify the cells. First sorting was performed with nano size immunomagnetic beads and followed by 2nd sorting where micron size immunomagnetic beads were used. The low-cost microfluidic platform is made of PMMA and glass including micro size gold pads. The developed microfluidic platform was optimized with cultured B type lymphoblast cells and tested with the samples of leukemia patients. The 8 bone marrow samples of 4 leukemia patients on the initial diagnosis and on the 15th day after the start of the chemotherapy treatment were tested both with the developed microfluidic platform and the flow cytometry. A 99% statistical agreement between the two methods shows that the microfluidic chip is able to monitor the decrease in the number of blast cells due to the chemotherapy. The experiments with the patient samples demonstrate that the developed system can perform relative measurements and have a potential to monitor the patient response to the applied therapy and to enable personalized dose adjustment.

Functional dextran amino acid ester particles derived from N-protected S-trityl-L-cysteine.

This work describes the derivatization of dextran using N-(tert-butyloxycarbonyl)-S-(trityl)-L-cysteine in the presence of N,N'-carbonyldiimidazole (CDI) as a coupling agent. Homogeneous reactions in dimethyl sulfoxide allowed for an efficient coupling of the amino acid derivative to the polymer backbone. Derivatization was confirmed by infrared and 13C NMR spectroscopy, size exclusion chromatography and elemental analysis. The presence of hydrophobic protecting groups resulted in a product that can be shaped into water-insoluble particles stable in an aqueous environment and non-toxic for lung epithelial cells. It is suggested that materials composed of ester bonds between amino acids and polysaccharides are useful for targeted drug delivery, bio-imaging or surface functionalization.

Micro-Nano Bioactive Glass Particles Incorporated Porous Scaffold for Promoting Osteogenesis and Angiogenesis in vitro.

Constructing the interconnected porous biomaterials scaffolds with osteogenesis and angiogenesis capacity is extremely important for efficient bone tissue engineering. Herein, we fabricated a bioactive micro-nano composite scaffolds with excellent in vitro osteogenesis and angiogenesis capacity, based on poly (lactic-co-glycolic acid) (PLGA) incorporated with micro-nano bioactive glass (MNBG). The results showed that the addition of MNBG enlarged the pore size, increased the compressive modulus (4 times improvement), enhanced the physiological stability and apatite-forming ability of porous PLGA scaffolds. The in vitro studies indicated that the PLGA-MNBG porous scaffold could enhance the mouse bone mesenchymal stem cells (mBMSCs) attachment, proliferation, and promote the expression of osteogenesis marker (ALP). Additionally, PLGA-MNBG could also support the attachment and proliferation of human umbilical vein endothelial cells (HUVECs), and significantly enhanced the expression of angiogenesis marker (CD31) of HUVECs. The as-prepared bioactive PLGA-MNBG nanocomposites scaffolds with good osteogenesis and angiogenesis probably have a promising application for bone tissue regeneration.

Promoting in vivo early angiogenesis with sub-micrometer strontium-contained bioactive microspheres through modulating macrophage phenotypes.

Early vascularization capacity of biomaterials plays an essential role in efficient wound healing and tissue regeneration, especially in large tissue tension implanting position such as bone augmentation. Strontium-contained silica-based bioactive materials have shown the role of promoting angiogenesis by stimulating osteoblasts to secrete angiogenesis related cytokines. However, osteoblasts have little effect on early angiogenesis due to the inflammatory reaction of implantation site. Here, for the first time, we found that the monodispersed strontium-contained bioactive glasses microspheres (SrBGM) could significantly promote the early angiogenesis through regulating macrophage phenotypes. After being stimulated with SrBGM in vitro, RAW cells (macrophages) presented a trend towards to M2 phenotype and expressed high level of platelet-derived growth factor-BB (PDGF-BB). Moreover, the RAW conditioned medium of SrBGM significantly enhanced the angiogenic capacity of HUVECs. The in vivo early vascularization studies showed that significant new vessels were observed at the center of SrBGM-based scaffolds after implantation for 1 week in a bone defect model of rats, suggesting their enhanced early vascularization. Due to the efficient vascularization, the in vivo new bone formation was promoted significantly. Our study may provide a novel strategy to promote the early vascularization of biomaterials through modulating the microphage phenotypes, which has wide applications in various tissue regeneration and wound healing.

Preparation and characterization of a composite biomaterial including starch micro/nano particles loaded chitosan gel.

Thermosensitive Chitosan hydrogels which can be injected into defects with minimally invasive approach were prepared. Also starch micro/nano particles were synthesized via water-in-oil (W/O) miniemulsion technique. The starch particles were incorporated into the chitosan hydrogel to prepare injectable thermosensitive hydrogel composites. Tube inverting method, compression tests, swelling studies, XRD, SEM, OM, DLS, UV-vis spectroscopy were used for investigations. Results revealed that increasing crosslinker and surfactant contents and stirring rate leads to particle size reduction. Particle size was modeled using design of experiments (DOE) via the response surface method (RSM). Due to analysis of variance (ANOVA), the particle sizes can be predicted by quadratic model within the design space. Gelation time and compressive modulus measurements showed the particles significant influence on the blend network density and hydrogel mechanical properties. Swelling measurements revealed that incorporation of starch particles in chitosan hydrogel increases its swelling coefficient significantly. The innovative architecture, namely micro/nano particles in gel can be considered as a dual delivery platform or smart scaffold for engineering of certain tissues.

Atomic Force Microscopy: A Powerful Tool to Address Scaffold Design in Tissue Engineering.

Functional polymers currently represent a basic component of a large range of biological and biomedical applications including molecular release, tissue engineering, bio-sensing and medical imaging. Advancements in these fields are driven by the use of a wide set of biodegradable polymers with controlled physical and bio-interactive properties. In this context, microscopy techniques such as Atomic Force Microscopy (AFM) are emerging as fundamental tools to deeply investigate morphology and structural properties at micro and sub-micrometric scale, in order to evaluate the in time relationship between physicochemical properties of biomaterials and biological response. In particular, AFM is not only a mere tool for screening surface topography, but may offer a significant contribution to understand surface and interface properties, thus concurring to the optimization of biomaterials performance, processes, physical and chemical properties at the micro and nanoscale. This is possible by capitalizing the recent discoveries in nanotechnologies applied to soft matter such as atomic force spectroscopy to measure surface forces through force curves. By tip-sample local interactions, several information can be collected such as elasticity, viscoelasticity, surface charge densities and wettability. This paper overviews recent developments in AFM technology and imaging techniques by remarking differences in operational modes, the implementation of advanced tools and their current application in biomaterials science, in terms of characterization of polymeric devices in different forms (i.e., fibres, films or particles).

New Preparative Approaches for Micro and Nano Drug Delivery Carriers.

The full success of pharmacological therapies is strongly depending on the use of suitable, efficient and smart drug delivery systems (DDSs). Thus DDSs development is one of the main challenges in pharmaceutical industry both to achieve tailored carrier systems based on drug features and to promote manufacturing innovations to reduce energetic resources, emissions, wastes and risks. Main functions of an ideal DDS are: to protect loaded active molecules from degradation in physiological environments; to deliver them in a controlled manner and towards specific organs or tissues, to allow the maintenance of drug concentration within therapeutic window. Smart features, such as those able to induce active molecule release upon the occurrence of specific physiological stimuli, are also desirable. Under the manufacturing point of view, the current industrial scenery is obliged to respond to the increasing market requirements and to the mandatory rules in sustainable productions such as raw material and energy savings. In this work a general framework on drug delivery systems preparation techniques is presented. In particular two sections on innovation in preparative approaches carried out are detailed. These latter involve the use of microwave and ultrasonic energy applied in the production of polymeric and lipidic delivery systems on micro- and nanometric scale. The novelties of these preparative approaches are emphasized and examples of developed drug delivery carriers, loaded with vitamins and drug mimicking siRNA, are shown.