A mechanistic study of the formation of polymer nanoparticles by the emulsification-diffusion technique

The mechanism of formation of polymer nanoparticles prepared by the emulsification-diffusion method was evaluated under different preparation conditions and by turbidimetry measurements. Biodegradable poly (D,L-lactic acid) was used as the polymer model. The results show that each emulsion droplet will form several nanoparticles and that the interfacial phenomena during solvent diffusion determine the size properties of the resulting colloid particles. These phenomena cannot be entirely explained by the convection effects caused by interfacial turbulence. We suggest that nanoparticle formation is due to diffusion alone, and we propose a mechanism based on the "diffusion-stranding” mechanism for spontaneous emulsification. In this mechanism, the diffusion of solvent causes local supersaturation near the interface, and nanoparticles are formed, due to the phase transformation and polymer aggregation that occur in these regions. This interpretation is supported by the turbidity measurements made at different polymer concentrations and stirring rate

Transdermal Delivery of Cytochrome C—A 12.4kDa Protein—Across Intact Skin by Constant-Current Iontophoresis

Purpose: To demonstrate the transdermal iontophoretic delivery of a small (12.4kDa) protein across intact skin. Materials and Methods: The iontophoretic transport of Cytochrome c (Cyt c) across porcine ear skin in vitro was investigated and quantified by HPLC. The effect of protein concentration (0.35 and 0.7mM), current density (0.15, 0.3 or 0.5mA.cm−2 applied for 8h) and competing ions was evaluated. Co-iontophoresis of acetaminophen was employed to quantify the respective contributions of electromigration (EM) and electroosmosis (EO). Results: The data confirmed the transdermal iontophoretic delivery of intact Cyt c. Electromigration was the principal transport mechanism, accounting for ∼90% of delivery; correlation between EM flux and electrophoretic mobility was consistent with earlier results using small molecules. Modest EO inhibition was observed at 0.5mA.cm−2. Cumulative permeation at 0.3 and 0.5mA.cm−2 was significantly greater than that at 0.15mA.cm−2; fluxes using 0.35 and 0.7mM Cyt c in the absence of competing ions (J tot  = 182.8 ± 56.8 and 265.2 ± 149.1μg.cm−2.h−1, respectively) were statistically equivalent. Formulation in PBS (pH8.2) confirmed the impact of competing charge carriers; inclusion of ∼170mM Na+ resulted in a 3.9-fold decrease in total flux. Conclusions: Significant amounts (∼0.9mg.cm−2 over 8h) of Cyt c were delivered non-invasively across intact skin by transdermal electrotranspor

Trachelomonas (Euglenophyta) from a eutrophic reservoir In Central Mexico

This study provides valuable information on the ultrastructure and environmental conditions of the Trachelomonas Ehr. (Euglenophyceae) genus in the Guadalupe Dam, a eutrophic reservoir located in the suburbs of Mexico City, which receives a considerable volume of wastewaters. Specimens were collected at surface level between November 2005 and May 2006. Using LM and SEM twelve taxa from phytoplankton were identified of which, 9 are new records for Mexico. The reservoir is warm monomictic, with basic pH values (7.4-10.1), a high concentration of chlorophyll a(18-101 microg l(-1), a permanent anoxic bottom, specific conductivity (K25) of 205 to 290 microS cm(-1), N-NO3, 0.19-1.2 mg l(-1) and P-PO4 0.22-1.6 mg l(-1). Water temperature was 15.6-23.0 degrees C. Most of the Trachelomonas species were found during the dry season, when concentrations of organic matter, nitrogen and phosphorus as well as the temperature were the highest. Higher species richness was also associated with the warmer months. This research contributes to increase our knowledge on Trachelomonas in Mexico and constitutes the first detailed description of lorica ultrastructure of 12 taxa that grow in a body of water with high concentration of nutrients and a moderate amount of mineral contents.Fil: Garduño Solorzano, Gloria. Universidad Nacional Autonoma de Mexico. Facultad de Estudios Superiores de Iztacala; MéxicoFil: Oliva Martinez, Maria Guadalupe. Universidad Nacional Autonoma de Mexico. Facultad de Estudios Superiores de Iztacala; MéxicoFil: Lugo Vázquez, Alfonso. Universidad Nacional Autonoma de Mexico. Facultad de Estudios Superiores de Iztacala; MéxicoFil: Mendoza Garfías, María Berenit. Universidad Nacional Autonoma de Mexico. Facultad de Estudios Superiores de Iztacala; MéxicoFil: Quintanar Zuñiga, Rafael Emiliano. Universidad Nacional Autonoma de Mexico. Facultad de Estudios Superiores de Iztacala; MéxicoFil: Conforti, Visitacion Teresa D.. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Biodiversidad y Biología Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Agglomeration of celecoxib by quasi emulsion solvent diffusion method: effect of stabilizer

Purpose: The quasi-emulsion solvent diffusion (QESD) has evolved into an effective technique to manufacture agglomerates of API crystals. Although, the proposed technique showed benefits, such as cost effectiveness, that is considerably sensitive to the choice of a stabilizer, which agonizes from a absence of systemic understanding in this field. In the present study, the combination of different solvents and stabilizers were compared to investigate any connections between the solvents and stabilizers. Methods: Agglomerates of celecoxib were prepared by QESD method using four different stabilizers (Tween 80, HPMC, PVP and SLS) and three different solvents (methyl acetate, ethyl acetate and isopropyl acetate). The solid state of obtained particles was investigated by differential scanning calorimetry (DSC) and Fourier transform infrared (FT-IR) spectroscopy. The agglomerated were also evaluated in term of production yield, distribution of particles and dissolution behavior. Results: The results showed that the effectiveness of stabilizer in terms of particle size and particle size distribution is specific to each solvent candidate. A stabilizer with a lower HLB value is preferred which actually increased its effectiveness with the solvent candidates with higher lipophilicity. HPMC appeared to be the most versatile stabilizer because it showed a better stabilizing effect compared to other stabilizers in all solvents used. Conclusion: This study demonstrated that the efficiency of stabilizers in forming the celecoxib agglomerates by QESD was influenced by the HLB of the stabilizer and lipophilicity of the solvents

Water dispersible microbicidal cellulose acetate phthalate film

BACKGROUND: Cellulose acetate phthalate (CAP) has been used for several decades in the pharmaceutical industry for enteric film coating of oral tablets and capsules. Micronized CAP, available commercially as "Aquateric" and containing additional ingredients required for micronization, used for tablet coating from water dispersions, was shown to adsorb and inactivate the human immunodeficiency virus (HIV-1), herpesviruses (HSV) and other sexually transmitted disease (STD) pathogens. Earlier studies indicate that a gel formulation of micronized CAP has a potential as a topical microbicide for prevention of STDs including the acquired immunodeficiency syndrome (AIDS). The objective of endeavors described here was to develop a water dispersible CAP film amenable to inexpensive industrial mass production. METHODS: CAP and hydroxypropyl cellulose (HPC) were dissolved in different organic solvent mixtures, poured into dishes, and the solvents evaporated. Graded quantities of a resulting selected film were mixed for 5 min at 37°C with HIV-1, HSV and other STD pathogens, respectively. Residual infectivity of the treated viruses and bacteria was determined. RESULTS: The prerequisites for producing CAP films which are soft, flexible and dispersible in water, resulting in smooth gels, are combining CAP with HPC (other cellulose derivatives are unsuitable), and casting from organic solvent mixtures containing ≈50 to ≈65% ethanol (EtOH). The films are ≈100 µ thick and have a textured surface with alternating protrusions and depressions revealed by scanning electron microscopy. The films, before complete conversion into a gel, rapidly inactivated HIV-1 and HSV and reduced the infectivity of non-viral STD pathogens >1,000-fold. CONCLUSIONS: Soft pliable CAP-HPC composite films can be generated by casting from organic solvent mixtures containing EtOH. The films rapidly reduce the infectivity of several STD pathogens, including HIV-1. They are converted into gels and thus do not have to be removed following application and use. In addition to their potential as topical microbicides, the films have promise for mucosal delivery of pharmaceuticals other than CAP

Statistička analiza nanokapsuliranja niskomolekularnog heparina

The objective of this study was to use Box-Behnken design (BBD) to investigate the influence of formulation variables on the properties of heparin-loaded poly(lactic-co-glycolic acid) (PLGA)-Eudragit-RLPO (E-RLPO) nanoparticles (NP) in terms of mean diameter (as size) and drug encapsulation efficiency. The NPs were prepared by the double emulsion solvent evaporation method. The independent variables were: X1 olymer mass ratio (PLGA:E-RLPO) in the oil phase, X2 concentration of polyvinyl alcohol (PVA) as emulsion stabilizer, and X3 volume of the external aqueous phase (W2). Particle size (analyzed by dynamic light scattering) and encapsulation efficiency (EE, estimated by spectrophotometry) were the investigated responses. The polynomial equation obtained from regression analysis of the reduced model (p = 0.0002, F = 25.7952 and R2 = 0.96) provided an excellent fit. The optimal size for the NP was found to be 134.2 ± 16.5 nm with formulation variables of 48.2:61.8, 0.321 (%, m/V) and 263 mL for X1, X2 and X3, respectively. Probably, due to electrostatic interaction between the negatively charged drug and the positively charged E-RLPO, the percent EE of heparin was between 74.4 ± 6.5 % (lowest value) and 92.1 ± 5.3 % (highest value). The data suggest that BBD is a useful tool in rational design of heparin-loaded NPs.Box-Behnkenovo dizajniranje (BBD) primijenjeno je za praćenje utjecaja formulacijskih varijabli na svojstva nanočestica (NP) s heparinom. Za izradu nanočestica korišten je kopolimer mliječne i glikolne kiseline (PLGA) i Eudragit-RLPO (E-RLPO). Nanočestice su pripravljene metodom dvostruke evaporacije otapala iz emulzije. Nezavisne varijable bile su: X1 omjer masa polimera (PLGA : E-RLPO) u uljnoj fazi, X2 koncentracija polivinil alkohola (PVA) kao stabilizatora emulzije i X3 volumen vanjske vodene faze (W2). Zavisne varijable bile su veličina čestica (analizirana pomoću dinamičkog rasapa svjetlosti) i učinkovitost inkapsuliranja (EE) (praćena spektrofotometrijski). Polinomska jednadžba dobivena regresijskom analizom reduciranog modela odlično je odgovarala (p = 0,0002, F = 25,7952 i R2 = 0,96). Optimalna veličina nanočestica bila je 134,2 ± 16,5 nm s formulacijskim varijablama 48,2:61,8, 0,321 (%, m/V) i 263 mL for X1, X2 odnosno X3. Vjerojatno je zbog elektrostatskih interakcija između negativno nabijene ljekovite tvari i pozitivno nabijenog E-RLPO učinkovitost inkapsuliranja heparina varirala od 74,4 ± 6,5 % (najniža vrijednost) do 92,1 ± 5,3 % (najviša vrijednost). Rezultati sugeriraju da je BBD vrlo korisno u racionalnom dizajniranju nanočestica s heparinom

Catalytic Cycle of Multicopper Oxidases Studied by Combined Quantum- and Molecular-Mechanical Free-Energy Perturbation Methods

We have used combined quantum mechanical and molecular mechanical free-energy perturbation methods in combination with explicit solvent simulations to study the reaction mechanism of the multicopper oxidases, in particular the regeneration of the reduced state from the native intermediate. For 52 putative states of the trinuclear copper cluster, differing in the oxidation states of the copper ions and the protonation states of water- and O2-derived ligands, we have studied redox potentials, acidity constants, isomerisation reactions, as well as water- and O2 binding reactions. Thereby, we can propose a full reaction mechanism of the multicopper oxidases with atomic detail. We also show that the two copper sites in the protein communicate so that redox potentials and acidity constants of one site are affected by up to 0.2 V or 3 pKa units by a change in the oxidation state of the other site

The PREVENTION Challenge: How Good Are Humans Predicting Lane Changes?

While driving on highways, every driver tries to be aware of the behavior of surrounding vehicles, including possible emergency braking, evasive maneuvers trying to avoid obstacles, unexpected lane changes, or other emergencies that could lead to an accident. In this paper, human's ability to predict lane changes in highway scenarios is analyzed through the use of video sequences extracted from the PREVENTION dataset, a database focused on the development of research on vehicle intention and trajectory prediction. Thus, users had to indicate the moment at which they considered that a lane change maneuver was taking place in a target vehicle, subsequently indicating its direction: left or right. The results retrieved have been carefully analyzed and compared to ground truth labels, evaluating statistical models to understand whether humans can actually predict. The study has revealed that most participants are unable to anticipate lane-change maneuvers, detecting them after they have started. These results might serve as a baseline for AI's prediction ability evaluation, grading if those systems can outperform human skills by analyzing hidden cues that seem unnoticed, improving the detection time, and even anticipating maneuvers in some cases.Comment: This work was accepted and presented at IEEE Intelligent Vehicles Symposium 202

Co-encapsulation of human serum albumin and superparamagnetic iron oxide in PLGA nanoparticles: Part I. Effect of process variables on the mean size

PLGA (poly d,l-lactic-co-glycolic acid) nanoparticles (NPs) encapsulating magnetite nanoparticles (MNPs) along with a model drug human serum albumin (HSA) were prepared by double emulsion solvent evaporation method. This Part I will focus on size and size distribution of prepared NPs, whereas encapsulation efficiency will be discussed in Part II. It was found that mean hydrodynamic particle size was influenced by five important process variables. To explore their effects, a five-factorial, three-level experimental design and statistical analysis were carried out using STATISTICA® software. Effect of process variables on the mean size of nanoparticles was investigated and finally conditions to minimize size of NPs were proposed. GAMS™/MINOS software was used for optimization. The mean hydrodynamic size of nanoparticles ranged from 115 to 329 nm depending on the process conditions. Smallest possible mean particle size can be achieved by using low polymer concentration and high dispersion energy (enough sonication time) along with small aqueous/organic volume ratio