Mucoadhesive Amphiphilic Methacrylic Copolymer-Functionalized Poly(epsilon-caprolactone) Nanocapsules for Nose-to-Brain Delivery of Olanzapine

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Relationship between composition and organizational levels of nanostructured systems formed by Oleth 10 and PPG-5-Ceteth-20 for potential drug delivery

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Surface engineering of silica nanoparticles for oral insulin delivery: characterization and cell toxicity studies

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Nanotechnology-based drug delivery systems for the treatment of Alzheimer's disease

Alzheimer's disease is a neurological disorder that results in cognitive and behavioral impairment. Conventional treatment strategies, such as acetylcholinesterase inhibitor drugs, often fail due to their poor solubility, lower bioavailability, and ineffective ability to cross the blood-brain barrier. Nanotechnological treatment methods, which involve the design, characterization, production, and application of nanoscale drug delivery systems, have been employed to optimize therapeutics. These nanotechnologies include polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, microemulsion, nanoemulsion, and liquid crystals. Each of these are promising tools for the delivery of therapeutic devices to the brain via various routes of administration, particularly the intranasal route. The objective of this study is to present a systematic review of nanotechnology-based drug delivery systems for the treatment of Alzheimer's disease.

Development and characterization of a biocompatible soybean oil-based microemulsion for the delivery of poorly water-soluble drugs

The aim of this work was the development and characterization of a biocompatible microemulsion (ME) containing soybean oil (O), phosphatidylcholine/sodium oleate/Eumulgin®HRE40 as the surfactant mixture (S) and water or buffer solution as the aqueous phase (W), for oral delivery of the poorly water-soluble drugs sulfamerazine (SMR) and indomethacin (INM). A wide range of combinations to obtain clear oil-in-water (o/w) ME was observed from pseudo-ternary phase diagrams, which was greater after the incorporation of both drugs, suggesting that they acted as stabilizers. Drug partition studies indicated a lower affinity of the drugs for the oil domain when they were ionized and with increased temperature, explained by the fact that both drugs were introduced inside the oil domain, determined by nuclear magnetic resonance. High concentrations of SMR and INM were able to be incorporated (22.0 and 62.3 mg/mL, respectively). The ME obtained presented an average droplet size of 100 nm and a negative surface charge. A significant increase in the release of SMR was observed with the ME with the highest percentage of O, because of the solubilizing properties of the ME. Also, a small retention effect was observed for INM, which may be explained by the differences in the partitioning properties of the drugs. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3535-3543, 2015.

Dendrimers as potential platform in nanotechnology-based drug delivery systems

The dendrimers of poly (amidoamine) (PAMAM) are nanoparticles which have proven succeed in transporting drugs due to high solubility, low toxicity and ability to control drugs release. Studies have explored the biological potential of dendrimers such as to transport genes, development of vaccines, antiviral, antibacterial and anticancer therapies. This review of literature on the PAMAM dendrimers discusses the architecture and general construction of dendrimers and intrinsic properties of the PAMAM. This study also describes how the PAMAM interact with many drugs and the potential of these macromolecules as well as drug nanocarriers in transdermal routes of administration, ocular, respiratory, oral and intravenous administration. Dendrimers promises good future prospects for the biomedicine.

Development and in vitro skin delivery of dexamethasone acetate-loaded surfactant-based systems

Topical corticosteroids, e.g., dexamethasone acetate (DMA), are extensively used to treat cutaneous inflammatory disorders even though their use is correlated with potential local and systemic side effects. The objective of this study was to develop and test the topical delivery of DMA-loaded surfactant based systems in vitro; these studies could guarantee a suitable delivery and therapeutic efficacy, as well as minimize DMA's side effects. A phase diagram was constructed using polyoxypropylene (5) polyoxyethylene (20) cetyl alcohol as the surfactant (S), isopropyl myristate as the oil phase (O) and water (W). The systems were characterized using polarization light microscopy (PLM), as well as rheological and small angle X-ray scattering (SAXS) measurements. Depending on the concentration of the constituents, it was possible to obtain microemulsions (MEs) and liquid crystalline mesophases (lamellar and hexagonal). These types of arrangement were verified using PLM measurements. The SAXS results revealed that increasing the W/S ratio led to ME, as well as lamellar (LAM) and hexagonal (HEX) arrangements. The MEs displayed typical Newtonian behavior while the LAM and HEX phases exhibited pseudoplasticity and plasticity, respectively. The MEs displayed excellent drug solubilization that was approximately 10-fold higher than was observed with the individual components. The in vitro cutaneous permeation studies using pig ear skin and analysis of the mechanical parameters (hardness, compressibility, cohesiveness and adhesiveness) were carried out with a HEX phase and O/W emulsion. The HEX phase achieved better drug permeation and retention in the skin while its mechanical properties were suitable for skin administration. PPG-5-CETETH-20-based systems may be a promising platform delivering DMA and other topical corticosteroids through the skin.

Development and analysis of formulations to the delivery of caffeine for the treatment of gynoid lipodystrophy

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Surfactant-based transdermal system for fluconazole skin delivery

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

A load-balancing spare capacity reallocation approach in service-rich SONET metro mesh networks

The next-generation SONET metro network is evolving into a service-rich infrastructure. At the edge of such a network, multi-service provisioning platforms (MSPPs) provide efficient data mapping enabled by Generic Framing Procedure (GFP) and Virtual Concatenation (VC). The core of the network tends to be a meshed architecture equipped with Multi-Service Switches (MSSs). In the context of these emerging technologies, we propose a load-balancing spare capacity reallocation approach to improve network utilization in the next-generation SONET metro networks. Using our approach, carriers can postpone network upgrades, resulting in increased revenue with reduced capital expenditures (CAPEX). For the first time, we consider the spare capacity reallocation problem from a capacity upgrade and network planning perspective. Our approach can operate in the context of shared-path protection (with backup multiplexing) because it reallocates spare capacity without disrupting working services. Unlike previous spare capacity reallocation approaches which aim at minimizing total spare capacity, our load-balancing approach minimizes the network load vector (NLV), which is a novel metric that reflects the network load distribution. Because NLV takes into consideration both uniform and non-uniform link capacity distribution, our approach can benefit both uniform and non-uniform networks. We develop a greedy loadbalancing spare capacity reallocation (GLB-SCR) heuristic algorithm to implement this approach. Our experimental results show that GLB-SCR outperforms a previously proposed algorithm (SSR) in terms of established connection capacity and total network capacity in both uniform and non-uniform networks.

Liquid Crystal Nanodispersions Enable the Cutaneous Delivery of Photosensitizer for Topical PDT: Fluorescence Microscopy Study of Skin Penetration

Topical photodynamic therapy (PDT) has been applied to almost all types of nonmelanoma skin cancer and numerous superficial benign skin disorders. Strategies to improve the accumulation of photosensitizer in the skin have been studied in recent years. Although the hydrophilic phthalocyanine zinc compound, zinc phthalocyanine tetrasulfonate (ZnPcSO4) has shown high photodynamic efficiency and reduced phototoxic side effects in the treatment of brain tumors and eye conditions, its use in topical skin treatment is currently limited by its poor skin penetration. In this study, nanodispersions of monoolein (MO)-based liquid crystalline phases were studied for their ability to increase ZnPcSO4 uptake by the skin. Lamellar, hexagonal and cubic crystalline phases were prepared and identified by polarizing light microscopy, and the nanodispersions were analyzed by dynamic light scattering. In vitro skin penetration studies were performed using a Franz's cell apparatus, and the skin uptake was evaluated in vivo in hairless mice. Aqueous dispersions of cubic and hexagonal phases showed particles of nanometer size, approximately 224 +/- 10 nm and 188 +/- 10 nm, respectively. In vitro skin retention experiments revealed higher fluorescence from the ZnPcSO4 in deeper skin layers when this photosensitizer was loaded in the hexagonal nanodispersion system when compared to both the cubic phase nanoparticles and the bulk crystalline phases (lamellar, cubic and hexagonal). The hexagonal nanodispersion showed a similar penetration behavior in animal tests. These results are important findings, suggesting the development of MO liquid crystal nanodispersions as potential delivery systems to enhance the efficacy of topical PDT.

The dialogic life-death in care delivery to adolescents with cancer

This study aims to understand the experience of adolescents with cancer, family and the health team regarding death in the healthcare context, in the light of Edgar Morin's proposed theoretical framework of complexity. Participants were 12 adolescents, 14 relatives and 25 health professionals. The interview was used for data collection. The discussion of data was guided by the dialogic life-death in the context of care to adolescents with cancer. It was observed that the singularity in the way the adolescent experiences time and faces death and the possibility that the family will lose a loved one may not be in accordance with the care the health team offers, considering structural, organizational and affective aspects. It is not enough for the team just to rationally make choices on the use of diagnostic-therapeutic devices, in line with predefined moments in the disease. Instead, a contextualized and sensitive understanding of each situation is needed.

Delivery Levels of Support Competencies to Organizational Eco-efficiency: a case study in an electro-electronics sector industry

This article aims to develop and implement a search tool which, through the perception of its respondents, allows assessing how eco-efficient an organization is based on the identification of delivery levels of support competencies to organizational eco-efficiency. A mixed (qualitative and quantitative) exploratory-descriptive research was conducted, from a case study in an 'ISE Company'. A semi-structured interview and pictures of verification were used as data collection instruments. The data were analyzed via documentary analysis and triangulation of information collected. It was inferred that at the 'ISE Company' professionals at the high-level of the organizational hierarchy recognize, in part, the growth of organizational actions that contribute to sustainability, which is not fully consistent with national publications on the subject. The result of the research showed that organizational strategies addressing eco-efficiency are partially aligned with the professional performance of the organization.

Counter-ion effect on surfactant-DNA gel particles as controlled DNA delivery systems

The ability to entrap drugs within vehicles and subsequently release them has led to new treatments for a number of diseases. Based on an associative phase separation and interfacial diffusion approach, we developed a way to prepare DNA gel particles without adding any kind of cross-linker or organic solvent. Among the various agents studied, cationic surfactants offered particularly efficient control for encapsulation and DNA release from these DNA gel particles. The driving force for this strong association is the electrostatic interaction between the two components, as induced by the entropic increase due to the release of the respective counter-ions. However, little is known about the influence of the respective counter-ions on this surfactant-DNA interaction. Here we examined the effect of different counter-ions on the formation and properties of the DNA gel particles by mixing DNA (either single-(ssDNA) or double-stranded (dsDNA)) with the single chain surfactant dodecyltrimethylammonium (DTA). In particular, we used as counter-ions of this surfactant the hydrogen sulfate and trifluoromethane sulfonate anions and the two halides, chloride and bromide. Effects on the morphology of the particles obtained, the encapsulation of DNA and its release, as well as the haemocompatibility of these particles are presented, using counter-ion structure and DNA conformation as controlling parameters. Analysis of the data indicates that the degree of counter-ion dissociation from the surfactant micelles and the polar/hydrophobic character of the counter-ion are important parameters in the final properties of the particles. The stronger interaction with amphiphiles for ssDNA than for dsDNA suggests the important role of hydrophobic interactions in DNA.

In Vitro Characterization of Chitosan Gels for Buccal Delivery of Celecoxib: Influence of a Penetration Enhancer

Celecoxib (Cx) shows high efficacy in the treatment of osteoarthritis and rheumatoid arthritis as a result of its high specificity for COX-2, without gastrolesivity or interference with platelet function at therapeutic concentrations. Besides of anti-inflammatory effects, Cx also has a potential role for oral cancer chemoprevention. For these conditions, oral administration in long-term treatment is a concern due to its systemic side effects. However, local application at the site of injury (e.g., buccal inflammation conditions or chemoprevention of oral cancer) is a promising way to reduce its toxicity. In this study, the in vitro characterization of mucoadhesive chitosan (CHT) gels associated to AzoneA (R) was assessed to explore the potential buccal mucosal administration of Cx in this tissue. Rheological properties of gels were analyzed by a rheometer with cone-plate geometry. In vitro Cx release and permeability studies used artificial membranes and pig cheek mucosa, respectively. Mucoadhesion were measured with a universal test machine. CHT gels (3.0%) containing 2.0% or 3.0% Az showed more appropriate characteristics compared to the others: pH values, rheology, higher amount of Cx retained in the mucosa, and minimal permeation through mucosa, besides the highest mucoadhesion values, ideal for buccal application. Moreover, the flux (J) and amounts of drug released decreased with increased CHT and Az concentrations. CHT gels (3.0%) associated with 2.0% or 3.0% Az may be considered potential delivery systems for buccal administration of Cx.