NO-cGMP-K+ Channels Pathways Participate in the Antihypertensive Effects of Attalea phalerata Martius ex Spreng Oil-Loaded Nanocapsules.

Attalea phalerata Martius ex Spreng is a palm tree that is widely distributed in the Central-West region of Brazil. In this study, we investigated whether the oil-loaded nanocapsules of A. phalerata (APON) have acute and long-lasting antihypertensive effects in male spontaneously hypertensive rats (SHR), as well as explored the underlying molecular mechanisms. APON was prepared using the interfacial polymer deposition method. The particle size, polydispersity index, and zeta potential were investigated using dynamic and electrophoretic light scattering. The antihypertensive effects of APON (administered at doses of 1, 3, and 10 mg/kg) were evaluated after acute intraduodenal administration and after 7 days of oral treatment. To investigate the molecular pathways involved, we used pharmacological antagonists and inhibitors that target prostaglandin/cyclic adenosine monophosphate, nitric oxide/cyclic guanosine monophosphate, and potassium channels. Both acute and prolonged administration of APON (at doses of 3 and 10 mg/kg) resulted in a significant reduction in systolic, diastolic, and mean arterial pressure. Prior treatment with a non-selective nitric oxide synthase inhibitor (Nω-nitro-L-arginine methyl ester), guanylyl cyclase inhibitor (methylene blue), or non-selective calcium-sensitive K+ channel blocker (tetraethylammonium) abolished the antihypertensive effects of APON. Our study showed that A. phalerata oil-loaded nanocapsules have a significant antihypertensive effect in SHR after both short-term and long-term (7-day) use. This effect seems to rely on the vascular endothelium function and involves the NO-cGMP-K+ channel pathway. This research suggests a new direction for future studies to definitively prove the therapeutic benefits of APON in treating cardiovascular disease.

Arabinoxylans matrixes as a potential material for drug delivery systems development - A bibliometric analysis and literature review.

Arabinoxylans (AX) have become a focal point in the pharmaceutical sector owing to their physicochemical, biological, and functional properties. The purpose of this paper was to present a summary of the utilization of AX as drug release matrices through a bibliometric analysis (BA) and a literature review to spotlight the AX functional characteristics and their technological applications to promote this line of research. The BA was carried out using data from a Web of Science database research, specifically emphasizing the analysis of authors' keywords. This approach was chosen due to its significance in comprehensively understanding a particular research field and its relevance for in-depth knowledge of a research field. The BA outcomes revealed limited information concerning the AX applications in both release matrices and as excipients in the formulation and development of drug delivery systems (DDS), so there is a need for additional scientific and technological research in these areas to address the existing information gaps. However, the literature review shows that the native and modified AX from different delivery release systems, such as macrogels (including films, tablets, and hard gelatin capsules) and multi-particulate systems (including micro and nanogels), present an excellent potential as release matrices of biomolecules and drugs, such as doxorubicin, diclofenac sodium, caffeine, gentamicin, tizanidine hydrochloride, and insulin. In conclusion, AX have a wide potential for application in the pharmaceutical industry, so this work is expected to be a reference point for future research by scientists, technologists, and entrepreneurs who cope with the subject.

Recent Biotechnological Applications of Polyhydroxyalkanoates (PHA) in the Biomedical Sector-A Review.

Petroleum-derived plastics are materials of great importance for the contemporary lifestyle, and are widely used commercially because they are low cost, resistant, malleable, and weightless, in addition to their hydrophobic character. However, some factors that confer the qualities of these materials also cause problems, mainly environmental, associated with their use. The COVID-19 pandemic aggravated these impacts due to the high demand for personal protective equipment and the packaging sector. In this scenario, bioplastics are environmentally positive alternatives to these plastics due to their applicability in several areas ranging from packaging, to biomedicine, to agriculture. Polyhydroxyalkanoates (PHAs) are biodegradable biopolymers usually produced by microorganisms as an energy reserve. Their structural variability provides a wide range of applications, making them a viable option to replace polluting materials. PHAs can be applied in various biotechnology sectors, such as producing drug carriers and scaffolds for tissue engineering. This review aimed to survey works published in the last five years on the study and biotechnological application of PHAs in the biomedical sector, exploring the versatility and advantages of their use and helping to understand how to enhance their application.

Development of Lipid Polymer Hybrid Drug Delivery Systems Prepared by Hot-Melt Extrusion.

This study sought to develop polymer-lipid hybrid solid dispersions containing the poorly soluble drug lopinavir (LPV) by hot-melt extrusion (HME). Hence, the lipid and polymeric adjuvants were selected based on miscibility and compatibility studies. Film casting was used to assess the miscibility, whereas thermal, spectroscopic, and chromatographic analyses were employed to evaluate drug-excipient compatibility. Extrudates were obtained and characterized by physicochemical tests, including in vitro LPV dissolution. Preformulation studies led to select the most appropriate materials, i.e., the polymers PVPVA and Soluplus®, the plasticizers polyethylene glycol 400 and Kolliphor® HS15, phosphatidylcholine, and sodium taurodeoxycholate. HME processing did not result in LPV degradation and significantly increased entrapment efficiency (93.8% ± 2.8 for Soluplus® extrudate against 19.8% ± 0.5 of the respective physical mixture). LPV dissolution was also increased from the extrudates compared to the corresponding physical mixtures (p < 0.05). The dissolution improvement was considerably greater for the Soluplus®-based formulation (24.3 and 2.8-fold higher than pure LPV and PVPVA-based extrudate after 120 min, respectively), which can be attributed to the more pronounced effects of HME processing on the average size and LPV solid-state properties in the Soluplus® extrudates. Transmission electron microscopy and chemical microanalysis suggested that the polymer-lipid interactions in Soluplus®-based formulation depended on thermal processing.

Biomaterials Based on Organic Polymers and Layered Double Hydroxides Nanocomposites: Drug Delivery and Tissue Engineering.

The development of biomaterials has a substantial role in pharmaceutical and medical strategies for the enhancement of life quality. This review work focused on versatile biomaterials based on nanocomposites comprising organic polymers and a class of layered inorganic nanoparticles, aiming for drug delivery (oral, transdermal, and ocular delivery) and tissue engineering (skin and bone therapies). Layered double hydroxides (LDHs) are 2D nanomaterials that can intercalate anionic bioactive species between the layers. The layers can hold metal cations that confer intrinsic biological activity to LDHs as well as biocompatibility. The intercalation of bioactive species between the layers allows the formation of drug delivery systems with elevated loading capacity and modified release profiles promoted by ion exchange and/or solubilization. The capacity of tissue integration, antigenicity, and stimulation of collagen formation, among other beneficial characteristics of LDH, have been observed by in vivo assays. The association between the properties of biocompatible polymers and LDH-drug nanohybrids produces multifunctional nanocomposites compatible with living matter. Such nanocomposites are stimuli-responsive, show appropriate mechanical properties, and can be prepared by creative methods that allow a fine-tuning of drug release. They are processed in the end form of films, beads, gels, monoliths etc., to reach orientated therapeutic applications. Several studies attest to the higher performance of polymer/LDH-drug nanocomposite compared to the LDH-drug hybrid or the free drug.

In Vitro Studies of Pegylated Magnetite Nanoparticles in a Cellular Model of Viral Oncogenesis: Initial Studies to Evaluate Their Potential as a Future Theranostic Tool.

Magnetic nanosystems represent promising alternatives to the traditional diagnostic and treatment procedures available for different pathologies. In this work, a series of biological tests are proposed, aiming to validate a magnetic nanoplatform for Kaposi's sarcoma treatment. The selected nanosystems were polyethylene glycol-coated iron oxide nanoparticles (MAG.PEG), which were prepared by the hydrothermal method. Physicochemical characterization was performed to verify their suitable physicochemical properties to be administered in vivo. Exhaustive biological assays were conducted, aiming to validate this platform in a specific biomedical field related to viral oncogenesis diseases. As a first step, the MAG.PEG cytotoxicity was evaluated in a cellular model of Kaposi's sarcoma. By phase contrast microscopy, it was found that cell morphology remained unchanged regardless of the nanoparticles' concentration (1-150 µg mL-1). The results, arising from the crystal violet technique, revealed that the proliferation was also unaffected. In addition, cell viability analysis by MTS and neutral red assays revealed a significant increase in metabolic and lysosomal activity at high concentrations of MAG.PEG (100-150 µg mL-1). Moreover, an increase in ROS levels was observed at the highest concentration of MAG.PEG. Second, the iron quantification assays performed by Prussian blue staining showed that MAG.PEG cellular accumulation is dose dependent. Furthermore, the presence of vesicles containing MAG.PEG inside the cells was confirmed by TEM. Finally, the MAG.PEG steering was achieved using a static magnetic field generated by a moderate power magnet. In conclusion, MAG.PEG at a moderate concentration would be a suitable drug carrier for Kaposi's sarcoma treatment, avoiding adverse effects on normal tissues. The data included in this contribution appear as the first stage in proposing this platform as a suitable future theranostic to improve Kaposi's sarcoma therapy.

Cell-Friendly Chitosan-Xanthan Gum Membranes Incorporating Hydroxyapatite Designed for Periodontal Tissue Regeneration.

In this work, a simple method was proposed to produce dense composite polysaccharide-based membranes to be used for guided tissue and guided bone regeneration. The mucoadhesive polysaccharides chitosan (C) and xanthan gum (X) were used to produce polyelectrolyte-based complex membranes. Hydroxyapatite (HA) was added to the formulation as a potential drug carrier, in C:X:HA mass proportions equal to 1:1:0.4, 1:1:2, and 1:1:10, and also to improve membranes bioactivity and biomimetic properties. FTIR analysis indicated successful incorporation of HA in the membranes and XRD analysis showed that no changes in the HA crystalline structure were observed after incorporation. The residual mass evaluated by TGA was higher for the formulation produced at the proportion 1:1:10. The membranes produced showed asymmetrical surfaces, with distinct roughness. Increasing the HA concentration increased the surface roughness. Greater in vitro proliferation of dental pulp mesenchymal stem cells was observed on the surface of the membrane with 1:1:10 C:X:HA proportion. However, the 1:1:2 formulation showed the most adequate balance of mechanical and biological properties. These results suggest that adding HA to the membranes can influence mechanical parameters as well as cell adhesion and proliferation, supporting the potential application of these materials in regenerative techniques and the treatment of periodontal lesions.

Gold Nanoparticles as Drug Carriers: The Role of Silica and PEG as Surface Coatings in Optimizing Drug Loading.

The use of gold nanoparticles as drug delivery systems has received increasing attention due to their unique properties, such as their high stability and biocompatibility. However, gold nanoparticles have a high affinity for proteins, which can result in their rapid clearance from the body and limited drug loading capabilities. To address these limitations, we coated the gold nanoparticles with silica and PEG, which are known to improve the stability of nanoparticles. The synthesis of the nanoparticles was carried out using a reduction method. The nanoparticles' size, morphology, and drug loading capacity were also studied. The SEM images showed a spherical and homogeneous morphology; they also showed that the coatings increased the average size of the nanoparticles. The results of this study provide insight into the potential of gold nanoparticles coated with silica and PEG as drug delivery systems. We used ibuprofen as a model drug and found that the highest drug load occurred in PEG-coated nanoparticles and then in silica-coated nanoparticles, while the uncoated nanoparticles had a lower drug loading capacity. The coatings were found to significantly improve the stability and drug load properties of the nanoparticles, making them promising candidates for further development as targeted and controlled release drug delivery systems.

Ketoconazole/calix[n]arenes-based compounds improve the antifungal activity against azole-resistant Candida isolates.

Ketoconazole (KTZ) is an antifungal agent; however, its bioavailability and therapeutic efficacy are reduced by the low aqueous solubility of the drug. Aiming at providing to improve the biopharmaceutical properties of KTZ, we studied the water-soluble different calix[n]arenes as carrier systems for KTZ. All calix[n]arene-KTZ tested showed in vitro antifungal activity superior or similar to free KTZ against Candida spp. The CX6Na/KTZ obtained by physical mixture and freeze-drying methods were the most active, decreasing KTZ concentrations required for growth inhibition against azole-resistant isolates (e.g., C. auris). Moreover, CX6Na/KTZ showed no toxic effect on Galleria mellonella larvae and the treatment of infected larvae with C. albicans and C. auris was effective at a lower dose compared with free KTZ. Thus, CX6Na/KTZ may have a potential approach to treat mycosis, especially by improvement of KTZ inhibitory activity against azole-resistant Candida.

Antiviral Potential of Naphthoquinones Derivatives Encapsulated within Liposomes.

HSV infections, both type 1 and type 2, are among the most widespread viral diseases affecting people of all ages. Their symptoms could be mild, with cold sores up to 10 days of infection, blindness and encephalitis caused by HSV-1 affecting immunocompetent and immunosuppressed individuals. The severe effects derive from co-evolution with the host, resulting in immune evasion mechanisms, including latency and growing resistance to acyclovir and derivatives. An efficient alternative to controlling the spreading of HSV mutations is the exploitation of new drugs, and the possibility of enhancing their delivery through the encapsulation of drugs into nanoparticles, such as liposomes. In this work, liposomes were loaded with a series of 2-aminomethyl- 3-hydroxy-1,4-naphthoquinones derivatives with n-butyl (compound 1), benzyl (compound 2) and nitrobenzene (compound 3) substituents in the primary amine of naphthoquinone. They were previously identified to have significant inhibitory activity against HSV-1. All of the aminomethylnaphthoquinones derivatives encapsulated in the phosphatidylcholine liposomes were able to control the early and late phases of HSV-1 replication, especially those substituted with the benzyl (compound 2) and nitrobenzene (compound 3), which yields selective index values that are almost nine times more efficient than acyclovir. The growing interest of the industry in topical administration against HSV supports our choice of liposome as a drug carrier of aminomethylnaphthoquinones derivatives for formulations of in vivo pre-clinical assays.

Langmuir-Blodgett monolayers holding a wound healing active compound and its effect in cell culture. A model for the study of surface mediated drug delivery systems.

Langmuir and Langmuir-Blodgett films holding a synthetic bioinspired wound healing active compound were used as drug-delivery platforms. Palmitic acid Langmuir monolayers were able to incorporate 2-methyltriclisine, a synthetic Triclisine derivative that showed wound healing activity. The layers proved to be stable and the nanocomposites were transferred to solid substrates. Normal human lung cells (Medical Research Council cell strain 5, MRC-5) were grown over the monomolecular Langmuir-Blodgett films that acted as a drug reservoir and delivery system. The proliferation and migration of the cells were clearly affected by the presence of 2-methyltriclisine in the amphiphilic layers. The methodology is proposed as a simple and reliable model for the study of the effects of bioactive compounds over cellular cultures.

Desenvolvimento e avaliação de nova preparação de anfotericina B e/ou cetoconazol em dispersão de bixina, pullulan e trealose / Development and evaluation of novel preparation of amphotericin B and/or ketoconazole in dispersion of bixin, pullulan and trehalose

Muitos pacientes acometidos por infecções fúngicas sucumbem devido a não eficácia dos antibióticos ou por toxicidade dos mesmos. Anfotericina B é um dos antifúngicos mais eficientes do mercado apesar de sua alta toxicidade, tem estrutura poliênica e é um composto insolúvel em água, sendo necessário o uso de adjuvantes e novas tecnologias para preparo de formulações eficazes. Cetoconazol é um composto imidazólico, também com ação antifúngica de grande espectro de ação e difícil solubilização em meio aquouso, porém solúvel somente em baixos valores de pH. Estudos têm demonstrado a utilização de bixina na preparação de dispersões aquosas de compostos insolúveis ou pouco solúveis em água. Bixina é o principal composto das cascas de semente de Bixa orellana (urucum), sendo um carotenoide insolúvel em água, porém, permite preparações na forma de nanodispersões aquosas com incorporação de fármacos apolares ou lipofílicos. O objetivo deste trabalho foi preparar anfotericina B e cetoconazol na forma de nanodispersões a partir de bixina, utilizando pullulan e trealose como adjuvantes e avaliar estabilidade e eficácia antimicrobiana por ensaios físico-químicos e microbiológicos. Pullulan é um polissacarídeo constituído por unidades de maltotriose, com propriedades adesivas e capacidade de formar biofilmes, enquanto trealose é um composto com duas unidades de glicose, com boa estabilidade em faixas de pH de 3 a 10 e capaz de suportar altas temperaturas, como processos de esterilização por calor úmido. Ensaios físico-químicos demonstraram boa manutenção das características das preparações propostas neste projeto, como, por exemplo, diâmetro hidrodinâmico e potencial zeta das estruturas das nanodispersões de bixina e antifúngicos e também eficácia antimicrobiana frente a Candida albicans ATCC 10231. Os resultados apresentam perspectivas para aprimoramentos de formulações com fármacos pouco solúveis ou insolúveis em água, pesquisa de novos biomateriais e outras aplicações nas áreas farmacêutica e cosmética

Many patients with fungal infections succumb due to ineffectiveness or toxicity of antibiotics. Amphotericin B is one of the most efficient antifungals on the market despite its high toxicity. It presents polyenic structure and is a water-insoluble compound. In this case, it is necessary to use adjuvants and new technologies to prepare effective formulations. Ketoconazole is an imidazolic compound, also with broad spectrum antifungal action and difficult solubilization in aqueous medium but it is soluble at low pH values. Studies have demonstrated the use of bixin in the preparation of aqueous dispersions of insoluble or poorly soluble compounds in water. Bixin is the main compound of Bixa orellana (annatto) seed husks, being a water-insoluble carotenoid, but it allows preparations in the form of aqueous nanodispersions with incorporation of apolar or lipophilic drugs. The objective of this work was to prepare amphotericin B and ketoconazole as nanodispersions from bixin, using pullulan and trehalose as adjuvants and to evaluate them under aspects of stability and efficacy by physicochemical and microbiological assays. Pullulan is a polysaccharide consisting of maltotriose units with adhesive properties and ability to form biofilms, while trehalose is a compound with two glucose units with good stability at pH ranges from 3 to 10 and capable of withstanding high temperatures such as processes of sterilization by moist heat. Physicochemical tests demonstrated good maintenance of the characteristics of the preparations proposed in this project, such as hydrodynamic diameter and zeta potential of bixin and antifungal nanodispersions and also antimicrobial efficacy against Candida albicans ATCC 10231. The results present prospects for improvement. of poorly soluble or water-insoluble drug formulations, research on new biomaterials and other applications in the pharmaceutical and cosmetic fields

Preparation and Characterization of Poloxamer 407 Solid Dispersions as an Alternative Strategy to Improve Benznidazole Bioperformance.

Benznidazole (BZL), the first line drug for Chagas disease treatment, presents a low solubility, limiting the possibilities for its formulation. In this work, solid dispersions' (SDs) technology was exploited to increase BZL kinetic solubility and dissolution rate, seeking for an improvement in its bioperformance. A physical mixture (PM) and an SD using Poloxamer 407 as carrier were prepared and characterized. Dissolution tests were performed, and data were analyzed with the lumped model, which allowed to calculate different parameters of pharmaceutical relevance. A bioactivity assay was also carried out to probe the SD anti-trypanocidal activity. Among the most relevant results, the initial dissolution rate of the BZL SD was near 3, 4 and about 400-fold faster than the PM, a commercial formulation (CF) and an extracted BZL, respectivley. The times needed for an 80% of drug dissolution were 3.6 (SD), 46.4 (PM), and 238.7 min (CF); while the dissolution efficiency values at 30 min were 85.2 (SD), 71.2 (PM), and 65.0% (CF). Survival curves suggested that using Poloxamer 407 as carrier did not alter the anti-trypanocidal activity of BZL. These results allow to conclude that SDs can be an effective platform for immediate release of BZL in an oral administration.

Solubility and dissolution enhancement of flurbiprofen by solid dispersion using hydrophilic carriers

ABSTRACT The intent of the current work is to study the effect of polyethylene glycol 8000 and polyethylene glycol 10000 as hydrophilic carriers on dissolution behaviour of flurbiprofen. In the present study, solvent evaporation method was used to prepare flurbiprofen solid dispersions and evaluated for physico-chemical properties, drug-carrier compatibility studies and dissolution behaviour of drug. Solubility studies showed more solubility in higher pH values and formulations SD4 and SD8 were selected to prepare the fast dissolving tablets. FTIR and DSC study showed no interaction and drug was dispersed molecularly in hydrophilic carrier. XRD studies revealed that there was change in the crystallinity of the drug. The results of In vitro studies showed SD8 formulation confer significant improvement (p<0.05) in drug release, Q20 was 99.08±1.35% compared to conventional and marketed tablets (47.31±0.74% and 56.86±1.91%). The mean dissolution time (MDT) was reduced to 8.79 min compared to conventional and marketed tablets (25.76 and 22.22 min.) indicating faster drug release. The DE (% dissolution efficiency) was increased by 2.5 folds (61.63%) compared to conventional tablets (23.71%). From the results, it is evident that polyethylene glycol solid dispersions in less carrier ratio may enhance the solubility and there by improve the dissolution rate of flurbiprofen.

Resveratrol-loaded nanocapsules inhibit murine melanoma tumor growth.

In this study, resveratrol-loaded nanocapsules were developed and its antitumor activity tested on a melanoma mice model. These nanocapsules were spherically-shaped and presented suitable size, negative charge and high encapsulation efficiency for their use as a modified-release system of resveratrol. Nanoencapsulation leads to the drug amorphization. Resveratrol-loaded nanoparticles reduced cell viability of murine melanoma cells. There was a decrease in tumor volume, an increase in the necrotic area and inflammatory infiltrate of melanoma when resveratrol-loaded nanocapsules were compared to free resveratrol in treated mice. Nanoencapsulation of resveratrol also prevented metastasis and pulmonary hemorrhage. This modified-release technology containing resveratrol can be used as a feasible approach in order to inhibit murine melanoma tumor growth.

Methotrexate Locally Released from Poly(ε-Caprolactone) Implants: Inhibition of the Inflammatory Angiogenesis Response in a Murine Sponge Model and the Absence of Systemic Toxicity.

In this study, the methotrexate (MTX) was incorporated into the poly(ε-caprolactone) (PCL) to design implants (MTX PCL implants) aiming the local treatment of inflammatory angiogenesis diseases without causing systemic side effects. Sponges were inserted into the subcutaneous tissue of mice as a framework for fibrovascular tissue growth. After 4 days, MTX PCL implants were also introduced, and anti-inflammatory, antiangiogenic, and antifibrogenic activities of the MTX were determined. MTX reduced the vascularization (hemoglobin content), the neutrophil, and monocyte/macrophage infiltration (MPO and NAG activities, respectively), and the collagen deposition in sponges. MTX reduced tumor necrosis factor-α and IL-6 levels, demonstrating its local antiangiogenic and anti-inflammatory effects. Furthermore, hepatotoxicity, nephrotoxicity, and myelotoxicity, which could be induced by the drug, were evaluated. However, MTX did not promote toxicity to these organs, as the levels of AST and ALT (hepatic markers) and creatinine and urea (renal markers) were not increased, and the complete blood count was not decreased. In conclusion, MTX PCL implants demonstrated to be effective in regulating the components of the inflammatory angiogenesis locally established, and presented an acceptable safety profile.

Cinnamic acid derived compounds loaded into liposomes: antileishmanial activity, production standardisation and characterisation.

Synthetic compounds derived from cinnamic acid were tested in cultures containing the promastigote form of Leishmania amazonensis and the dimethylsulphoxide solution of B2 compound (2.0 mg/mL) led to a 92% decrease of leishmania in 96 h of treatment. Then, different liposomal systems (diameters ∼200 nm) were prepared by the extrusion method in the presence and absence of compounds studied. DSC thermograms of the liposomes in the presence of these compounds caused changes in ΔH, Tm and ΔT1/2, compared to controls, indicating that there was an interaction of the compounds with the lipid bilayer. Assays with negatively charged liposomal systems containing these drugs in L. amazonensis cultures led to a 50-80% decrease in the number of leishmanias with a concentration to 100 times lower when compared to the B2 initial test. These liposomal systems are promoting more interaction and delivery of the compounds and proved to be an efficient, stable and promising system.

Methotrexate Locally Released from Poly(e-Caprolactone) Implants: Inhibition of the Inflammatory Angiogenesis Response in a Murine Sponge Model and the Absence of Systemic Toxicity.

In this study, the methotrexate (MTX) was incorporated into the poly(e-caprolactone) (PCL) to design implants (MTX PCL implants) aiming the local treatment of inflammatory angiogenesis diseases without causing systemic side effects. Sponges were inserted into the subcutaneous tissue of mice as a framework for fibrovascular tissue growth. After 4days, MTX PCL implants were also introduced, and anti-inflammatory, antiangiogenic, and antifibrogenic activities of the MTX were determined. MTX reduced the vascularization (hemoglobin content), the neutrophil, and monocyte/macrophage infiltration (MPO and NAG activities, respectively), and the collagen deposition in sponges. MTX reduced tumor necrosis factor-a and IL-6 levels, demonstrating its local antiangiogenic and anti-inflammatory effects. Furthermore, hepatotoxicity, nephrotoxicity, and myelotoxicity, which could be induced by the drug, were evaluated. However, MTX did not promote toxicity to these organs, as the levels of AST and ALT (hepatic markers) and creatinine and urea (renal markers) were not increased, and the complete blood count was not decreased. In conclusion, MTX PCL implants demonstrated to be effective in regulating the components of the inflammatory angiogenesis locally established, and presented an acceptable safety profile. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3731-3742, 2015.

Effect of cosurfactant on the supramolecular structure and physicochemical properties of non-ionic biocompatible microemulsions / Efeito de cotensoativo na obtenção e nas propriedades físico-químicas de microemulsões não iônicas

Microemulsions are transparent, homogeneous and thermodynamically stable systems, formed spontaneously under a specific set of experimental conditions from mixtures of water and oil phases stabilized by a surfactant or a mixture of surfactant and cosurfactant. These systems exhibit some unique properties that make them particularly interesting as delivery systems, as much for the oral as for the topical route. In the present work, we have studied the domain of existence of non-ionic microemulsion systems within pseudo-ternary phase diagrams. The results show a large area of microemulsion domain for O/W and W/O microemulsions. Depending on the proportion of components the apparent viscosity of the systems varied significantly. We have found that the presence of ethanol as cosurfactant affects the physical properties particularly the apparent viscosity and relative density. Analysis of the data indicated that the studied systems behave as non-Newtonian pseudoplastic shear-thinning fluids appropriated for pharmaceutical and cosmetic applications.

Microemulsões são sistemas transparentes, homogêneos e termodinamicamente estáveis, formados espontaneamente, sob determinadas condições experimentais, a partir de misturas de água e fase oleosa estabilizadas por tensoativo ou por mistura de tensoativo e cotensoativo. Esses sistemas exibem propriedades diferenciadas, as quais os tornam particularmente interessantes como sistemas de liberação, principalmente pelas vias oral e tópica. Nesse trabalho foi estudado o domínio da existência de sistemas microemulsionados não iônicos, através de diagramas de fase pseudo-ternários. Os resultados mostraram uma grande área de domínio para microemulsões O/A e A/O, onde A e O referem-se a água e óleo, respectivamente. Dependendo das proporções dos componentes, a viscosidade aparente dos sistemas variou significantemente. Foi determinado que a presença de etanol como cotensoativo modificou as propriedades físico-químicas dos sistemas, particularmente da viscosidade aparente e da densidade relativa. A análise dos dados mostrou que o sistema estudado comporta-se como um fluido não-Newtoniano pseudoplástico próprio para aplicações farmacêuticas e cosméticas.