Development and characterization of PLA nanoparticles as carriers for topical delivery

Nanoparticles are seen today as one of the best approaches for the delivery of drugs into the skin. Poly (Lactic Acid) (PLA) is biocompatible and biodegradable and already approved for clinical use. Thus, this work aimed to study the effect of several parameters on the properties of PLA nanoparticles (PLA-NPs) intended for topical delivery. The yield of nanoparticles formation and entrapment efficiencies of lipophilic and hydrophilic model compounds in PLA-NPs were assessed. We evaluated the effects of mechanical stirring, solvent composition and presence of tri-bloc polymers on the protocol for the production of PLA-NPs. The best protocol provided a monodispersed population of non-cytotoxic spherical particles of !150 nm and a yield of nanoparticles formation of !90%. This formulation also proved to be efficient in the encapsulation of lipophilic and hydrophilic model compounds (>80%). The best protocol for the production of PLA-NPs includes a nanoprecipitation step, which is easily up scalable

Formulações micelares proteicas e respectivo método de produção

The present invention describes micellar protein formulations for the controlled release of active ingredients, and method for preparing the same. The invention describes a new micelle composition for use in pharmaceuticals, cosmetics and detergents. In particular, it describes micelle formation formulations that comprise: an aqueous phase containing a protein or a natural or synthetic peptide; a lipophilic phase containing a hydrophobic compound; an adjuvant dissolved in the aqueous phase to regulate the size and stability of the micelles; the size of the micelles varying from 30 to 5000 nm, preferably from 30 to 100 nm, wherein the micelles can be obtained by two different methods, namely using ultrasound or a high-pressure homogeniser. The preparation method involves two distinct phases: an aqueous phase and a lipophilic phase. The aqueous phase can be water or any buffer that is best suitable for a given use, such as an aqueous solution of bovine serum albumen (BSA); human serum albumen (HSA); silk fibroin or a polypeptide fibroin.A presente invenção descreve em formulações micelares proteicas para libertação controlada de agentes e respetivo método de produção. A invenção descreve numa nova composição de micelas para aplicações farmacêuticas, cosméticas e 0 o0 detergência. Nomeadamente, formulações para a formação de micelas que compreendem: · uma fase aquosa contendo uma proteína ou um péptido natural ou sintético; · uma fase lipofílica que compreende um composto hidrofóbico; · um agente adjuvante dissolvido na fase aquosa que regula o tamanho e estabilidade das micelas; em que os tamanhos das referidas micelas varia entre 30 a 5000 nm, de preferência de 30-100 nm, as referidas micelas podem ser obtidas a partir de duas metodologias diferentes, nomeadamente ultra-sons ou homogeneizador de alta pressão. O método de preparação envolve duas fases distintas: fase aquosa e fase lipofílica. A fase aquosa pode ser água ou qualquer tampão que mais se adeque para uma determinada aplicação, como por exemplo uma solução aquosa de albumina sérica bovina (BSA); albumina sérica humana (HSA); fibroína da seda ou de um polipéptido.Universidade do Minh

Functionalization of gauzes with liposomes entrapping an anti-inflammatory drug: a strategy to improve wound healing

From ancientness, suitable materials have been developed to cover the wounds in order to prevent infections and promote proper wound healing. In this study, the successful development of functionalized nonwoven gauzes with liposomes entrapping anti-inflammatory piroxicam is reported. Piroxicam is a non-steroidal anti-inflammatory drug (NSAID) that can suppress a persistent inflammatory response, leading to improved wound healing. The results demonstrated that the highest NSAID concentration released is achieved when gauzes were previously cationized with poly(diallyldimethylammonium chloride) (PDDA) and high concentration of phospholipid (≈3000 μM) and multilamellar liposomes (MLVs) were used. MLVs were also the best vehicle considering their biocompatibility with skin human fibroblasts, where no toxicity was observed for neither of the tested conditions. The developed functionalized gauzes can be, therefore, a good strategy to treat chronic wounds.Helena Ferreira, Teresa Matama and Carla Silva thank POPH/FSE for co-financing and FCT for fellowships SFRH/BPD/38939/2007, SFRH/BPD/47555/2008, SFRH/BPD/46515/2008, respectively. This work was supported by FEDER through POFC - COMPETE and by national funds from FCT through the project PEst-C/BIA/UI4050/2011

In vitro design of a novel lytic bacteriophage cocktail with therapeutic potential against organisms causing diabetic foot infections

In patients with diabetes mellitus, foot infections pose a significant risk. These are complex infections commonly caused by Staphylococcus aureus, Pseudomonas aeruginosa and Acinetobacter baumannii, all of which are potentially susceptible to bacteriophages. Here, we characterized five bacteriophages that we had determined previously to have antimicrobial and wound-healing potential in chronic S. aureus, P. aeruginosa and A. baumannii infections. Morphological and genetic features indicated that the bacteriophages were lytic members of the family Myoviridae or Podoviridae and did not harbour any known bacterial virulence genes. Combinations of the bacteriophages had broad host ranges for the different target bacterial species. The activity of the bacteriophages against planktonic cells revealed effective, early killing at 4 h, followed by bacterial regrowth to pre-treatment levels by 24 h. Using metabolic activity as a measure of cell viability within established biofilms, we found significant cell impairment following bacteriophage exposure. Repeated treatment every 4 h caused a further decrease in cell activity. The greatest effects on both planktonic and biofilm cells occurred at a bacteriophage : bacterium input multiplicity of 10. These studies on both planktonic cells and established biofilms allowed us to better evaluate the effects of a high input multiplicity and a multiple-dose treatment protocol, and the findings support further clinical development of bacteriophage therapy.supported by TechnoPhage S.A. and Tecnifar; Foundation for Science and Technology (PTDC/SAUMIC/122816/2010 – ‘Biofilms in diabetic foot: microbial virulence characterization and cross-talk of major isolates’); FCT PhD fellowship (SFRH/BD/72872/2010); FCT ‘Ciência 2007’ programmeinfo:eu-repo/semantics/publishedVersio

Idiopathic pulmonary fibrosis associated with pulmonary vein thrombosis: a case report

BACKGROUND: Pulmonary vein thrombosis represents a potentially fatal disease. This syndrome may clinically mimic pulmonary embolism but has a different investigation strategy and prognosis. Pulmonary vein thrombosis is difficult to diagnose clinically and usually requires a combination of conventionally used diagnostic modalities. CASE PRESENTATION: The authors report a case of a 78-year-old previously healthy female presenting with collapse and shortness of breath. Serum biochemistry revealed acute kidney injury, positive D-dimmer's and increased C reactive protein. Chest radiography demonstrated volume loss in the right lung. The patient was started on antibiotics and also therapeutic doses of low molecular weight heparin. The working diagnosis included community acquired pneumonia & pulmonary embolism. A computed tomography pulmonary angiogram was performed to confirm the clinical suspicions of pulmonary embolism. This demonstrated a thrombus in the pulmonary vein, with associated fibrosis and volume loss of the right lower lobe. A subsequent thrombophilia screen revealed a positive lupus anticoagulant antibody and rheumatoid factor and also decreased anti thrombin III and protein C levels. The urine protein/creatinine ratio was found to be 553 mg/mmol. CONCLUSION: The diagnosis of this patient was therefore of idiopathic pulmonary fibrosis associated with pulmonary vein thrombosis. Whether or not the pulmonary vein thrombosis was a primary cause of the fibrosis or a consequence of it was unclear. There are few data on the management of pulmonary vein thrombosis, but anticoagulation, antibiotics, and, in cases of large pulmonary vein thrombosis, thrombectomy or pulmonary resection have been used

Insights on the mechanism of formation of protein microspheres in a biphasic system

Microspheres of bovine serum albumin (BSA) and silk fibroin are produced by applying ultrasound in a biphasic system consisting of an aqueous protein solution and an organic solvent. The protein microspheres are dispersed in an aqueous media where the protein remains at the interface covering the organic solvent. This only occurs when high shear forces are applied that induce changes to force the protein to the interface. Fourier transform infrared results indicate a large increase in the content of the β-sheet during the formation of silk fibroin microspheres. Molecular dynamics simulations show a clear adaption on the 3D structure of BSA when stabilized at the interface, without major changes in secondary structure. Further studies demonstrate that high water content, oil solvents, and larger peptides with separated and clear hydrophobic and hydrophilic areas lead to more stable and smaller spheres. This is the first time that these results are presented. We also present herein the rationale to produce tailored protein microspheres with a controlled size, controlled charge, and increased stability.This work was supported by Lidwine Project-Multifunctional medical textiles for wound (e.g., Decubitus) prevention and improved wound healing NMP2-CT-2006-026741. H.F. thanks POPH/FSE for cofinancing and FCT for Fellowship SFRH/BPD/38939/2007. We acknowledge Silvia Cappellozza from "Sezione Specializzata per la Bachicoltura" for the supply of silk cocoons

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat