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1.  Relaxation processes in hybrid organic-inorganic polymer nanosystems polymerized in situ 
Nanoscale Research Letters  2014;9(1):217.
The relaxation processes of hybrid organic-inorganic polymer nanosystems (OIS) synthesized by joint polymerization of organic and inorganic components were studied using methods of differential scanning calorimetry (DSC), dynamic mechanical thermal analysis (DMTA), and broadband dielectric relaxation spectroscopy (DRS). The organic component was a mixture of two products: high-molecular-weight macrodiisocyanate (MDI) with low reactivity and low-molecular-weight isocyanate-containing modifier poly(isocyanate) (PIC) with high reactivity. Sodium silicate (SS) was used as inorganic component. The structures of the OIS obtained were in the form of hybrids with covalently connected building blocks and interpenetrating networks: weakly cross-linked network MDI/SS and highly cross-linked network PIC/SS. Depending on the MDI/PIC ratio, one of the networks was prevailing and created a continuous structure with domains of second network.
PACS
61.25.hk; 82.35.Lr; 64.70.pj
doi:10.1186/1556-276X-9-217
PMCID: PMC4019787  PMID: 24872804
Hybrid polymers; Organic-inorganic nanosystems; Joint polymerization; Interpenetrating networks; Relaxation phenomena
2.  Non-Viral Delivery and Therapeutic Application of Small Interfering RNAs 
Acta Naturae  2013;5(3):35-53.
RNA interference (RNAi) is a powerful method used for gene expression regulation. The increasing knowledge about the molecular mechanism of this phenomenon creates new avenues for the application of the RNAi technology in the treatment of various human diseases. However, delivery of RNA interference mediators, small interfering RNAs (siRNAs), to target cells is a major hurdle. Effective and safe pharmacological use of siRNAs requires carriers that can deliver siRNA to its target site and the development of methods for protection of these fragile molecules from in vivo degradation. This review summarizes various strategies for siRNA delivery, including chemical modification and non-viral approaches, such as the polymer-based, peptide-based, lipid-based techniques, and inorganic nanosystems. The advantages, disadvantages, and prospects for the therapeutic application of these methods are also examined in this paper.
PMCID: PMC3848066  PMID: 24303201
small interfering RNA; RNA interference; non-viral delivery
3.  Preparation and evaluation of antimicrobial activity of nanosystems for the control of oral pathogens Streptococcus mutans and Candida albicans 
Background
Diseases that affect the buccal cavity are a public health concern nowadays. Chlorhexidine and nystatin are the most commonly used drugs for the control of buccal affections. In the search for more effective antimicrobials, nanotechnology can be successfully used to improve the physical chemical properties of drugs whilst avoiding the undesirable side effects associated with its use. Herein described are studies using nystatin and chlorhexidine with sodium montmorillonite (MMTNa), and chlorhexidine with β-cyclodextrin and two derivatives methyl-β-cyclodextrin and hydroxypropyl-β-cyclodextrin in the development of antimicrobial nanosystems.
Methods
The nanosystems were prepared by kneading and solubilization followed by freeze-drying technique. The nanosystems were characterized by X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR). Nanosystem antimicrobial activity against Streptococcus mutans and Candida albicans strains was evaluated with inhibition halo analysis.
Results
The nanocarriers MMTNa and cyclodextrins showed good yields. XRPD, FTIR, and DSC analysis confirmed the proposed nanosystems formation and the suitability of the production methods. The nanosystems that showed best antimicrobial effect were chlorhexidine gluconate (CHX) and cyclodextrin inclusion complexes and CHX:MMTNa 60% cation exchange capacity – 24 hours.
Conclusion
The nanosystem formulations present higher stability for all chlorhexidine inclusion complexes compared with pure chlorhexidine. The nystatin nanosystems have the potential to mask the bitter taste, justifying subsequent in-vivo studies. For these reasons, further studies are being carried out to evaluate their application in professional formulations.
doi:10.2147/IJN.S25667
PMCID: PMC3218573  PMID: 22114490
sodium montmorillonite; chlorhexidine gluconate; buccal diseases; nanotechnology; cyclodextrins
4.  Nanosystems for simultaneous imaging and drug delivery to T cells 
The AAPS Journal  2007;9(2):E171-E180.
The T-cell response defines the pathogenesis of many common chronic disease states, including diabetes, rheumatoid arthritis, and transplant rejection. Therefore, a diagnostic strategy that visualizes this response can potentially lead to early therapeutic intervention, avoiding catastrophic organ failure or prolonged sickness. In addition, the means to deliver a drug dose to those cells in situ with the same specificity used to image those cells would provide for a powerful therapeutic alternative for many disease states involving T cells. In this report, we review emerging nanosystems that can be used for simultaneous tracking and drug delivery to those cells. Because of their versatility, these systems—which combine specific receptor targeting with an imaging agent and drug delivery—are suited to both basic science and applications, from developing therapeutic strategies for autoimmune and alloimmune diseases, to noninvasive tracking of pathogenic T-cell migration.
doi:10.1208/aapsj0902019
PMCID: PMC2751406  PMID: 17614359
T cells; noninvasive imaging; drug delivery; nanoparticles
5.  AFM, ESEM, TEM, and CLSM in liposomal characterization: a comparative study 
An outstanding aspect of pharmaceutical nanotechnology lies in the characterization of nanocarriers for targeting of drugs and other bioactive agents. The development of microscopic techniques has made the study of the surface and systems architecture more attractive. In the field of pharmaceutical nanosystems, researchers have collected vital information on size, stability, and bilayer organization through the microscopic characterization of liposomes. This paper aims to compare the results obtained by atomic force microscopy, environmental scanning electron microscopy, transmission electron microscopy, and confocal laser scanning microscopy to point out the limits and advantages of these applications in the evaluation of vesicular systems. Besides this comparative aim, our work proposes a simple confocal laser scanning microscopy procedure to rapidly and easily detect the liposomal membrane.
doi:10.2147/IJN.S14615
PMCID: PMC3065801  PMID: 21468358
atomic force microscopy; transmission electron microscopy; environmental scanning electron microscopy; confocal laser scanning microscopy
6.  Silver nanoparticles are broad-spectrum bactericidal and virucidal compounds 
The advance in nanotechnology has enabled us to utilize particles in the size of the nanoscale. This has created new therapeutic horizons, and in the case of silver, the currently available data only reveals the surface of the potential benefits and the wide range of applications. Interactions between viral biomolecules and silver nanoparticles suggest that the use of nanosystems may contribute importantly for the enhancement of current prevention of infection and antiviral therapies. Recently, it has been suggested that silver nanoparticles (AgNPs) bind with external membrane of lipid enveloped virus to prevent the infection. Nevertheless, the interaction of AgNPs with viruses is a largely unexplored field. AgNPs has been studied particularly on HIV where it was demonstrated the mechanism of antiviral action of the nanoparticles as well as the inhibition the transmission of HIV-1 infection in human cervix organ culture. This review discusses recent advances in the understanding of the biocidal mechanisms of action of silver Nanoparticles.
doi:10.1186/1477-3155-9-30
PMCID: PMC3199605  PMID: 21812950
Silver Nanoparticles; Virucides; Bactericides; HIV/AIDS; Antibacterial agents
7.  Biocompatible nanocomposite for PET/MRI hybrid imaging 
A novel nanocarrier system was designed and developed with key components uniquely structured at the nanoscale for early cancer diagnosis and treatment. In order to perform magnetic resonance imaging, hydrophilic superparamagnetic maghemite nanoparticles (NPs) were synthesized and coated with a lipophilic organic ligand. Next, they were entrapped into polymeric NPs made of biodegradable poly(lactic-co-glycolic acid) linked to polyethylene glycol. In addition, resulting NPs have been conjugated on their surface with a 2,2′-(7-(4-((2-aminoethyl)amino)-1-carboxy-4-oxobutyl)-1,4,7-triazonane-1,4-diyl)diacetic acid ligand for subsequent 68Ga incorporation. A cell-based cytotoxicity assay has been employed to verify the in vitro cell viability of human pancreatic cancer cells exposed to this nanosystem. Finally, in vivo positron emission tomography-computerized tomography biodistribution studies in healthy animals were performed.
doi:10.2147/IJN.S38107
PMCID: PMC3526150  PMID: 23271907
maghemite nanoparticles; organic coating; polymeric nanoparticles; magnetic resonance imaging; radiolabeling; positron emission tomography
8.  Nanowire systems: technology and design 
Nanosystems are large-scale integrated systems exploiting nanoelectronic devices. In this study, we consider double independent gate, vertically stacked nanowire field effect transistors (FETs) with gate-all-around structures and typical diameter of 20 nm. These devices, which we have successfully fabricated and evaluated, control the ambipolar behaviour of the nanostructure by selectively enabling one type of carriers. These transistors work as switches with electrically programmable polarity and thus realize an exclusive or operation. The intrinsic higher expressive power of these FETs, when compared with standard complementary metal oxide semiconductor technology, enables us to realize more efficient logic gates, which we organize as tiles to realize nanowire systems by regular arrays. This article surveys both the technology for double independent gate FETs as well as physical and logic design tools to realize digital systems with this fabrication technology.
doi:10.1098/rsta.2013.0102
PMCID: PMC3928901  PMID: 24567471
nanosystems; nanoelectronics; nanowire transistors; controllable polarity; regular arrays; logic synthesis
9.  Formulation and Evaluation of a Salted-out Isoniazid-loaded Nanosystem 
AAPS PharmSciTech  2008;9(1):174-181.
The purpose of this study was to develop a drug-loaded nanosystem that has the ability to achieve flexible yet rate-controlled release of model drug isoniazid (INH) employing either an aqueous or emulsion-based salting-out approach. Formulation conditions were aimed at reducing the polymeric size with subsequent rate-modulated INH release patterns from the polymeric nanosystem. The emulsion-based salted-out nanosystems had particle sizes ranging from 77–414 nm and a zeta potential of −24 mV. The dispersant dielectric constant was set at 78.5 and a conductivity of 3.99 mS/cm achieved. The reduced nanosystem size of the aqueous-based approach has demonstrated an intrinsically enhanced exposure of methacrylic acid-ethyl acrylate to zinc sulphate which was employed as a crosslinking reagent. This resulted in robustly interconnected polymeric supports in which INH was efficiently embedded and subsequently released. The multi-layer perceptron data obtained showed that the aqueous and emulsion-based salting out approaches had Power (law) (MSE = 0.020) and Linear (MSE = 0.038) relationships, respectively. Drug release from the nanosystems occurred in two phases with an initial burst-release in aqueous-based nanosystems (30–100%) and significantly lower bursts observed in emulsion-based nanosystems (20–65%) within the first 2 h. This was followed by a gradual exponential release phase over the remaining 12 h. The nanosystems developed demonstrated the ability to control the release of INH depending on the formulation approach adopted.
doi:10.1208/s12249-007-9016-6
PMCID: PMC2976898  PMID: 18446479
crosslinking; drug release; methacrylic acid-ethyl acrylate; nanoparticles; tuberculosis
10.  Functionalized Nanosystems for Targeted Mitochondrial Delivery 
Mitochondrion  2011;12(2):190-201.
Mitochondrial dysfunction including oxidative stress and DNA mutations underlies the pathology of various diseases including Alzheimer’s disease and diabetes, necessitating the development of mitochondria targeted therapeutic agents. Nanotechnology offers unique tools and materials to target therapeutic agents to mitochondria. As discussed in this paper, a variety of functionalized nanosystems including polymeric and metallic nanoparticles as well as liposomes are more effective than plain drug and non-functionalized nanosystems in delivering therapeutic agents to mitochondria. Although the field is in its infancy, studies to date suggest the superior therapeutic activity of functionalized nanosystems for treating mitochondrial defects.
doi:10.1016/j.mito.2011.11.001
PMCID: PMC3299903  PMID: 22138492
Mitochondrial Targeted Delivery; Nanotechnology; Liposomes; Polymeric Nanoparticles; Metallic Nanoparticles
11.  Polysaccharide Nanosystems for Future Progress in Cardiovascular Pathologies 
Theranostics  2014;4(6):579-591.
Natural polysaccharides have received a lot of attention in the biomedical field. Indeed, sources of polysaccharides, extracted or produced from plants, bacteria, fungi or algae, are diverse and renewable. Moreover, recent progresses in polysaccharide chemistry and nanotechnologies allow elaborating new dedicated nanosystems. Polysaccharide-based nanosystems may be designed for interacting in several biological processes. In particular, the atherothrombotic pathology is highly concerned by polysaccharide-mediated recognition. Atherothrombotic diseases, regardless of the anatomical localization, remain the main causes of morbidity and mortality in the industrialized world. This review intends to provide an overview on polysaccharide-based nanosystems as drug delivery systems and targeted contrast agents for molecular imaging with an emphasis on the treatment and imaging of cardiovascular pathologies.
doi:10.7150/thno.7688
PMCID: PMC3982129  PMID: 24723980
Polysaccharides; Nanosystems; Atherothrombosis; Drug delivery; Molecular imaging.
12.  THE DISTRIBUTION OF THE WATER-SOLUBLE INORGANIC ORTHOPHOSPHATE IONS WITHIN THE CELL: ACCUMULATION IN THE NUCLEUS  
The Journal of Cell Biology  1969;42(3):754-765.
Lead acetate treatment of unfixed cells immobilizes the intracellular water-soluble, inorganic orthophosphate ions as microcrystalline lead hydroxyapatite precipitates (see reference 1). These precipitates have been analyzed with the electron microprobe. A much higher concentration of phosphorus has been found in the nucleoli of maize root tip cells fixed in lead acetate-glutaraldehyde (organic phosphorus plus inorganic orthophosphate), as compared to the nucleoli of roots fixed in glutaraldehyde alone (organic phosphorus). The concentration of the inorganic orthophosphate pool in these nucleoli is three to five times as high as the concentration of the macromolecular organic phosphate. Since nearly all of the latter is in RNA, the concentration of inorganic phosphate in the nucleolus is calculated to be roughly 0.5–0.8 M. About 30%—and up to 50%—of the total cellular inorganic phosphate is accumulated in the nucleolus since the mean concentration per cell is about 10-2 M. In the extranucleolar part of the nucleus the mean concentration was estimated by densitometry to be roughly six times less than in the nucleolus (⩽ 0.1 M), and appears more concentrated in the nucleoplasm than in the condensed chromatin. While there is no direct evidence for the concentration in the cytoplasm, it certainly must be much lower than the mean cellular level (i.e., < 10-2 M) since the nucleus is about 10% of the total cell volume. The implications of this compartmentation in the intact cell are discussed in connection with (A) the availability of orthophosphate ions for the cytoplasm in those processes in which these ions affect the rate of enzymatic reactions, and (B) protein nucleic acid interactions within the nucleus and nucleolus.
PMCID: PMC2107709  PMID: 5801427
13.  Control of heme and cytochrome P-450 metabolism by inorganic metals, organometals and synthetic metalloporphyrins. 
The heme-cytochrome P-450 complexes represent sensitive metabolic systems for examining the biological impact of metals on important cellular functions. Many metals, both in the inorganic form and bound to organic moieties, potently induce heme oxygenase, the rate limiting enzyme of heme degradation. The resulting increase in the rate of heme breakdown is reflected in a marked depression of cellular cytochrome P-450 content and impairment of the oxidative metabolism of natural and foreign chemicals dependent on this hemeprotein. Organometal complexes do not mimic in all their aspects the actions of the inorganic elements which they contain. For example, organotins, in contrast to inorganic tin, produce a prolonged induction response of heme oxygenase in the liver but not in the kidney. Co-protoporphyrin is a much more potent inducer of heme oxygenase in liver than is inorganic cobalt; and Sn-protoporphyrin inhibits heme oxygenase activity nearly completely, whereas inorganic tin is a powerful inducer of the renal enzyme. Contrasting effects on heme metabolism exist as well within the metalloporphyrin species as demonstrated by the effects in vivo of Co-protoporphyrin and Sn-protoporphyrin on heme oxygenase activity; the former induces the enzyme whereas the latter potently inhibits it. In vitro, however, both compounds competitively inhibit heme oxidation activity. These differences, among others which characterize metal actions in vivo and in vitro attest to the importance of pharmacokinetic, adaptive and other host factors in defining the responses of the heme-cytochrome P-450 systems to the impact of metals in the whole animal.
Images
PMCID: PMC1568282  PMID: 6548701
14.  THE ACCUMULATION OF ELECTROLYTES  
The Journal of General Physiology  1935;18(3):283-300.
Analyses have been made of the inorganic constituents of the juices expressed from the leaves of Rheum, Rumex, and Oxalis. It has been shown that in all cases there is a large excess of inorganic cations over anions in the sap, the average ratio of cations to anions being 3.8 (Part 1, p. 239). The ash analyses of plant tissues (chiefly leaves) reported in the literature have been examined critically, and it has been shown that the preponderance of inorganic cations over inorganic anions in the ash and in the sap is general. It has been concluded that the excess of inorganic cations is consistent with the view that cations pass into the protoplasm chiefly in the form of hydroxides, and are accumulated either in the form of organic salts (such as the oxalates) or in non-polar linkage. It has been concluded that practically all the potassium and sodium found in plant ash must have been present originally in the form of soluble ionogenic compounds, but that a considerable part of the calcium and magnesium may have been present originally in the form of insoluble salts or as components of non-polar compounds. The methods whereby the cations, particularly potassium, may have been accumulated have been discussed, and it has been concluded that as it does not seem very probable that they enter chiefly as nitrates or bicarbonates we may suppose that they go in to a large extent as hydrates: this is highly probable in the case which has been most carefully investigated (Valonia).
PMCID: PMC2141357  PMID: 19872843
15.  Overview of the main methods used to combine proteins with nanosystems: absorption, bioconjugation, and encapsulation 
The latest development of protein engineering allows the production of proteins having desired properties and large potential markets, but the clinical advances of therapeutical proteins are still limited by their fragility. Nanotechnology could provide optimal vectors able to protect from degradation therapeutical biomolecules such as proteins, enzymes or specific polypeptides. On the other hand, some proteins can be also used as active ligands to help nanoparticles loaded with chemotherapeutic or other drugs to reach particular sites in the body. The aim of this review is to provide an overall picture of the general aspects of the most successful approaches used to combine proteins with nanosystems. This combination is mainly achieved by absorption, bioconjugation and encapsulation. Interactions of nanoparticles with biomolecules and caveats related to protein denaturation are also pointed out. A clear understanding of nanoparticle-protein interactions could make possible the design of precise and versatile hybrid nanosystems. This could further allow control of their pharmacokinetics as well as activity, and safety.
PMCID: PMC2819905  PMID: 20161986
nanoparticles; drug delivery; proteins; polypeptides; absorption; bioconjugation; encapsulation
16.  PET/NIRF/MRI Triple Functional Iron Oxide Nanoparticles 
Biomaterials  2010;31(11):3016-3022.
Engineered nanoparticles with theranostic functions have attracted a lot of attention for their potential role in the dawning era of personalized medicine. Iron oxide nanoparticles (IONPs), with their advantages of being non-toxic, biodegradable and inexpensive, are candidate platforms for the build-up of theranostic nanostructures; however, progress in using them has been limited largely due to inefficient drug loading and delivery. In the current study, we utilized dopamine to modify the surface of IONPs, yielding nanoconjugates that can be easily encapsulated into human serum albumin (HSA) matrices (clinically utilized drug carriers). This nanosystem is well-suited for dual encapsulation of IONPs and drug molecules, because the encapsulation is achieved in a way that is similar to common drug loading. To assess the biophysical characteristics of this novel nanosystem, the HSA coated IONPs (HSA-IONPs) were dually labeled with 64Cu-DOTA and Cy5.5, and tested in a subcutaneous U87MG xenograft mouse model. In vivo positron emission tomography (PET)/near-infrared fluorescence (NIRF)/magnetic resonance imaging (MRI) tri-modality imaging, and ex vivo analyses and histological examinations were carefully conducted to investigate the in vivo behavior of the nanostructures. With the compact HSA coating, the HSA-IONPs manifested a prolonged circulation half-life; more impressively, they showed massive accumulation in lesions, high extravasation rate, and low uptake of the particles by macrophages at the tumor area.
doi:10.1016/j.biomaterials.2010.01.010
PMCID: PMC2838491  PMID: 20092887
iron oxide nanoparticle (IONP); magnetic resonance imaging (MRI); positron emission tomography (PET); near-infrared fluorescence (NIRF) imaging; enhanced permeability and retention (EPR) effect
17.  Nanoparticle-based theranostic agents 
Advanced drug delivery reviews  2010;62(11):1064-1079.
Theranostic nanomedicine is emerging as a promising therapeutic paradigm. It takes advantage of the high capacity of nanoplatforms to ferry cargo and loads onto them both imaging and therapeutic functions. The resulting nanosystems, capable of diagnosis, drug delivery and monitoring of therapeutic response, are expected to play a significant role in the dawning era of personalized medicine, and much research effort has been devoted toward that goal. A convenience in constructing such function-integrated agents is that many nanoplatforms are already, themselves, imaging agents. Their well developed surface chemistry makes it easy to load them with pharmaceutics and promote them to be theranostic nanosystems. Iron oxide nanoparticles, quantum dots, carbon nanotubes, gold nanoparticles and silica nanoparticles, have been previously well investigated in the imaging setting and are candidate nanoplatforms for building up nanoparticle-based theranostics. In the current article, we will outline the progress along this line, organized by the category of the core materials. We will focus on construction strategies and will discuss the challenges and opportunities associated with this emerging technology.
doi:10.1016/j.addr.2010.07.009
PMCID: PMC2988080  PMID: 20691229
Theranostics; drug delivery; gene delivery; nanomedicine; molecular imaging; iron oxide nanoparticles; quantum dots; gold nanoparticles; carbon nanotubes; silica nanoparticles
18.  Do new Ethical Issues Arise at Each Stage of Nanotechnological Development? 
Nanoethics  2011;6(1):29-37.
The literature concerning ethical issues associated with nanotechnologies has become prolific. However, it has been claimed that ethical problems are only at stake with rather sophisticated nanotechnologies such as active nanostructures, integrated nanosystems and heterogeneous molecular nanosystems, whereas more basic nanotechnologies such as passive nanostructures mainly pose technical difficulties. In this paper I argue that fundamental ethical issues are already at stake with this more basic kind of nanotechnologies and that ethics impacts every kind of nanotechnologies, already from the simplest kind of engineered nanoproducts. These ethical issues are mainly associated with the social desirability of nanotechnologies, with the difficulties to define nanotechnologies properly, with the important uncertainties surrounding nanotechnologies, with the threat of ‘nano-divide’, and with nanotechnology as ‘dual-use technology’.
doi:10.1007/s11569-011-0137-8
PMCID: PMC3343232  PMID: 22611458
Ethics; Equity; Dual-use technology; Generations of nanotechnologies; Informed consent; Nano-divide; Nanotechnologies; Precautionary principle; Risk; Social desirability; Uncertainty; Philosophy; Ethics; Philosophy of Science; Philosophy of Technology; Nanotechnology
19.  Hybrid nanostructured coating for increased resistance of prosthetic devices to staphylococcal colonization 
Prosthetic medical device-associated infections are responsible for significant morbidity and mortality rates. Novel improved materials and surfaces exhibiting inappropriate conditions for microbial development are urgently required in the medical environment. This study reveals the benefit of using natural Mentha piperita essential oil, combined with a 5 nm core/shell nanosystem-improved surface exhibiting anti-adherence and antibiofilm properties. This strategy reveals a dual role of the nano-oil system; on one hand, inhibiting bacterial adherence and, on the other hand, exhibiting bactericidal effect, the core/shell nanosystem is acting as a controlled releasing machine for the essential oil. Our results demonstrate that this dual nanobiosystem is very efficient also for inhibiting biofilm formation, being a good candidate for the design of novel material surfaces used for prosthetic devices.
doi:10.1186/1556-276X-8-6
PMCID: PMC3599461  PMID: 23281840
20.  Fabrication and Intracellular Delivery of Doxorubicin/Carbonate Apatite Nanocomposites: Effect on Growth Retardation of Established Colon Tumor 
PLoS ONE  2013;8(4):e60428.
In continuing search for effective treatments of cancer, the emerging model aims at efficient intracellular delivery of therapeutics into tumor cells in order to increase the drug concentration. However, the implementation of this strategy suffers from inefficient cellular uptake and drug resistance. Therefore, pH-sensitive nanosystems have recently been developed to target slightly acidic extracellular pH environment of solid tumors. The pH targeting approach is regarded as a more general strategy than conventional specific tumor cell surface targeting approaches, because the acidic tumor microclimate is most common in solid tumors. When nanosystems are combined with triggered release mechanisms in endosomal or lysosomal acidic pH along with endosomolytic capability, the nanocarriers demonstrated to overcome multidrug resistance of various tumors. Here, novel pH sensitive carbonate apatite has been fabricated to efficiently deliver anticancer drug Doxorubicin (DOX) to cancer cells, by virtue of its pH sensitivity being quite unstable under an acidic condition in endosomes and the desirable size of the resulting apatite-DOX for efficient cellular uptake as revealed by scanning electron microscopy. Florescence microscopy and flow cytometry analyses demonstrated significant uptake of drug (92%) when complexed with apatite nanoparticles. In vitro chemosensitivity assay revealed that apatite-DOX nanoparticles executed high cytotoxicity in several human cancer cell lines compared to free drugs and consequently apatite-DOX-facilitated enhanced tumor inhibitory effect was observed in colorectal tumor model within BALB/cA nude mice, thereby shedding light on their potential applications in cancer therapy.
doi:10.1371/journal.pone.0060428
PMCID: PMC3629059  PMID: 23613726
21.  Nanostructured systems containing babassu (Orbignya speciosa) oil as a potential alternative therapy for benign prostatic hyperplasia 
The oil of babassu tree nuts (Orbignya speciosa) is a potential alternative for treatment and prophylaxis of benign prostatic hyperplasia. Improved results can be obtained by drug vectorization to the hyperplastic tissue. The main objective of this work was the preparation and characterization of poly(lactic-co-glycolic acid) (PLGA) nanoparticle and clay nanosystems containing babassu oil (BBS). BBS was extracted from the kernels of babassu tree nuts and characterized by gas chromatography-mass spectrometry as well as 1H and 13C nuclear magnetic resonance. BBS-clay nanosystems were obtained by adding polyvinylpyrrolidone, Viscogel B8®, and BBS at a 2:1:1 mass ratio and characterized by X-ray diffraction, thermogravimetric analysis, infrared spectroscopy, and laser diffraction. The PLGA-BBS nanoparticles were prepared by the precipitation-solvent evaporation method. Mean diameter, polydispersity, zeta potential, and scanning electron microscopic images of the nanosystems were analyzed. Thermogravimetric analysis showed successful formation of the nanocomposite. PLGA nanoparticles containing BBS were obtained, with a suitable size that was confirmed by scanning electron microscopy. Both nanostructured systems showed active incorporation yields exceeding 90%. The two systems obtained represent a new and potentially efficient therapy for benign prostatic hyperplasia.
doi:10.2147/IJN.S47731
PMCID: PMC3753148  PMID: 23990721
babassu oil; nanocomposite; poly(lactic-co-glycolic acid); nanoparticles; benign prostatic hyperplasia; treatment; nanotechnology
22.  Critical evaluation of biodegradable polymers used in nanodrugs 
Use of biodegradable polymers for biomedical applications has increased in recent decades due to their biocompatibility, biodegradability, flexibility, and minimal side effects. Applications of these materials include creation of skin, blood vessels, cartilage scaffolds, and nanosystems for drug delivery. These biodegradable polymeric nanoparticles enhance properties such as bioavailability and stability, and provide controlled release of bioactive compounds. This review evaluates the classification, synthesis, degradation mechanisms, and biological applications of the biodegradable polymers currently being studied as drug delivery carriers. In addition, the use of nanosystems to solve current drug delivery problems are reviewed.
doi:10.2147/IJN.S47186
PMCID: PMC3753153  PMID: 23990720
biodegradable polymers; nanoparticles; drug delivery; cellular uptake; biomedical applications
23.  Magnetic Nanosystem for Cancer Therapy Using Oncocalyxone A, an Antitomour Secondary Metabolite Isolated from a Brazilian Plant 
This paper describes the investigation and development of a novel magnetic drug delivery nanosystem (labeled as MO-20) for cancer therapy. The drug employed was oncocalyxone A (onco A), which was isolated from Auxemma oncocalyx, an endemic Brazilian plant. It has a series of pharmacological properties: antioxidant, cytotoxic, analgesic, anti-inflammatory, antitumor and antiplatelet. Onco A was associated with magnetite nanoparticles in order to obtain magnetic properties. The components of MO-20 were characterized by XRD, FTIR, TGA, TEM and Magnetization curves. The MO-20 presented a size of about 30 nm and globular morphology. In addition, drug releasing experiments were performed, where it was observed the presence of the anomalous transport. The results found in this work showed the potential of onco A for future applications of the MO-20 as a new magnetic drug release nanosystem for cancer treatment.
doi:10.3390/ijms140918269
PMCID: PMC3794780  PMID: 24013376
drug delivery; cancer therapy; magnetic nanoparticles; oncocalyxone A
24.  In vivo and in vitro evaluation of octyl methoxycinnamate liposomes 
Solar radiation causes damage to human skin, and photoprotection is the main way to prevent these harmful effects. The development of sunscreen formulations containing nanosystems is of great interest in the pharmaceutical and cosmetic industries because of the many potential benefits. This study aimed to develop and evaluate an octyl methoxycinnamate (OMC) liposomal nanosystem (liposome/OMC) to obtain a sunscreen formulation with improved safety and efficacy by retaining OMC for longer on the stratum corneum.
Methods
The liposome/OMC nanostructure obtained was tested for enzymatic hydrolysis with lipase from Rhizomucor miehei and biodistribution with liposomes labeled with technetium-99m. The liposome/OMC formulation was then incorporated in a gel formulation and tested for ocular irritation using the hen’s egg test-chorio-allantoic membrane (HET-CAM) assay, in vitro and in vivo sun protection factor, in vitro release profile, skin biometrics, and in vivo tape stripping.
Results
The liposome/OMC nanosystem was not hydrolyzed from R. miehei by lipase. In the biodistribution assay, the liposome/OMC formulation labeled with technetium-99m had mainly deposited in the skin, while for OMC the main organ was the liver, showing that the liposome had higher affinity for the skin than OMC. The liposome/OMC formulation was classified as nonirritating in the HET-CAM test, indicating good histocompatibility. The formulation containing liposome/OMC had a higher in vivo solar photoprotection factor, but did not show increased water resistance. Inclusion in liposomes was able to slow down the release of OMC from the formulation, with a lower steady-state flux (3.9 ± 0.33 μg/cm2/hour) compared with the conventional formulation (6.3 ± 1.21 μg/cm2/hour). The stripping method showed increased uptake of OMC in the stratum corneum, giving an amount of 22.64 ± 7.55 μg/cm2 of OMC, which was higher than the amount found for the conventional formulation (14.57 ± 2.30 μg/cm2).
Conclusion
These results indicate that liposomes are superior carriers for OMC, and confer greater safety and efficacy to sunscreen formulations.
doi:10.2147/IJN.S51383
PMCID: PMC3864883  PMID: 24376350
sunscreen; liposome; tape stripping; technetium-99-m; lipase
25.  Molecular crowding shapes gene expression in synthetic cellular nanosystems 
Nature nanotechnology  2013;8(8):602-608.
Summary
The integration of synthetic and cell-free biology has made tremendous strides towards creating artificial cellular nanosystems using concepts from solution-based chemistry: only the concentrations of reacting species modulate gene expression rates. However, it is known that macromolecular crowding, a key feature of natural cells, can dramatically influence biochemical kinetics by volume exclusion effects that reduce diffusion rates and enhance binding rates of macromolecules. Here, we demonstrate that macromolecular crowding can increase the robustness of gene expression through integrating synthetic cellular components of biological circuits and artificial cellular nanosystems. In addition, we reveal how ubiquitous cellular modules, including genetic components, a negative feedback loop, and the size of crowding molecules, can fine tune gene circuit response to molecular crowding. By bridging a key gap between artificial and living cells, our work has implications for efficient and robust control of both synthetic and natural cellular circuits.
doi:10.1038/nnano.2013.132
PMCID: PMC3951305  PMID: 23851358
molecular crowding; synthetic biology; gene regulation; artificial cells; robustness

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