André L. Tessaro

Formulation of Aluminum Chloride Phthalocyanine in Pluronic™ P-123 and F-127 Block Copolymer Micelles: Photophysical properties and Photodynamic Inactivation of Microorganisms

Aluminum Chloride Phthalocyanine (AlPcCl) can be used as a photosensitizer (PS) for Photodynamic Inactivation of Microorganisms (PDI). The AlPcCl showed favorable characteristics for PDI due to high quantum yield of singlet oxygen (ΦΔ) and photostability. Physicochemical properties and photodynamic inactivation of AlPcCl incorporated in polymeric micelles of tri‐block copolymer (P‐123 and F‐127) against microorganisms Staphylococcus aureus, Escherichia coli and Candida albicans were investigated in this work. Previously, it was observed that the AlPcCl undergoes self‐aggregation in F‐127, while in P‐123 the PS is in a monomeric form suitable for PDI. Due to the self‐aggregation of AlPcCl in F‐127, this formulation did not show any effect on these microorganisms. On the other hand, AlPcCl formulated in P‐123 was effective against S. aureus and C. albicans and the death of microorganisms was dependent on the PS concentration and illumination time. Additionally, it was found that the values of PS concentration and illumination time to eradicate 90% of the initial population of microorganisms (IC90 and D90, respectively) were small for the AlPcCl in P‐123, showing the effectiveness of this formulation for PDI.

Influences of experimental parameters on the stability of a benzoporphyrin drug in water/ethanol mixtures: a statistical approach investigation

The benzoporphyrin derivative, named B3B, is a promising new drug for application in photodynamic therapy. In aqueous organic solvent mixtures, B3B, can be used in topical application for superficial diseases, like for skin cancer. In this paper, the self-aggregation phenomena of porphyrin molecules in aqueous media was investigated using a chemometric tool to evaluate the effects of experimental variables on the stability of the B3B monomer in water/ethanol mixtures. A 23 factorial design was employed which permitted determination of the magnitude of experimental parameters which influence aggregation of the drug at different pHs using the minimum number of experiments. At first, the pKa values of the B3B in water/ethanol mixtures were determined by spectrophotometric measurements, resulting in pKa1 = 3.3 and pKa2 = 5.7, corresponding to the imino nitrogens and carboxylic groups, respectively. The experimental variables (B3B concentration, time and water/ethanol composition) were evaluated in three protonation states of the drug, at pH 7.0, 4.1 and 2.6. The two levels (low and high) were set up at: time 5 (-) and 360 minutes (+); [B3B] 4.4 × 10-6(-) and 26.5 × 10-6M (+); and water content in ethanol 40 (-) and 60% (+). The main parameter that determines the magnitude of the effects seems to be the charge component of B3B, which can be modulated by the pH. The results from the 23 fractional design indicated that the main variable inducing B3B aggregation is the water percentage in ethanol at each pH selected. The magnitude of this effect was pronounced at pH 4.1 where the carboxylic and nitrogen free base forms of B3B are maintained. The factors of time and [B3B], despite being small, are not insignificant. Finally, the effect of water content was investigated in a wide range of water percentage in these three pHs.

Aggregation of aluminum phthalocyanine hydroxide in water/ethanol mixtures

Phthalocyanines (Pc) are synthetic compounds of interest in various fields. However, their high hydrophobicity promotes the undesirable aggregation process in aqueous media. Studies carried out with aluminum phthalocyanine hydroxide (AlPcOH) in different water/ethanol mixtures (v/v) have shown that in proportions of water lower than 30% the Pc is in the monomeric form. At 40 and 50% water/ethanol there was formation of dimers linked by hydrogen bonding or Al-O-Al bridged, while in percentages of water higher than 60% the aggregation process is complex, with multiple equilibria and higher-order aggregates (J-type).

Autoagregação da 5,10,15,20-tetrakis(4-metoxifenil)porfirina (tmpp): estudos espectroscópicos e análises multivariadas

In this work, the spectroscopic properties of 5,10,15,20-tetrakis(4-methoxyphenyl)porphyrin (TMPP) in solvents of different polarities and water/ethanol mixtures were studied by electronic absorption spectroscopy and resonance light scattering associated with statistical analysis. The molar absorption coefficient and emission maximum of TMPP were dependent on solvent polarity. In the water/ethanol mixture, TMPP remained monomeric up to 25% of water, when it reaches its critical aggregation percentage. Oblique head-to-tail aggregate was found at intermediate water content (35 - 55%), while formation of a J-type aggregate was observed at higher water content (> 60%).

Physico-chemical properties of meso-tetrakis(p-methoxyphenyl)porphyrin (TMPP) incorporated into pluronicTM p-123 and f-127 polymeric micelles

The physicochemical properties (solubilization, structural organization and stability) of meso-tetrakis(p-methoxyphenyl)porphyrin (TMPP), a promising photosensitizer for photodynamic therapy, solubilized in polymeric micelles of tri-block copolymers PluronicTM P-123 and F-127, were studied. The formulations obtained by the solid dispersion method led to monomerization of TMPP in these copolymers. Solubility studies showed that P-123 solubilizes double the photosensitizer than F-127. The self-aggregation phenomenon was affected by the [TMPP]/[poloxamer] ratio and medium temperature. The decrease in the temperature of these systems promoted the formation of different kinds of TMPP aggregates intrinsically connected with the structural changes occurring in the micelles.

Self-aggregation processes of 1,6-diphenyl-1,3,5-hexatriene in water/ethanol mixtures with high water percentages.

This work describes the behavior of 1,6-diphenyl-1,3,5-hexatriene (DPH) in ethanol/water mixtures. The dependence of DPH photophysical properties (absorption and fluorescence emission) on the water percentage in ethanol indicates that DPH undergoes self-aggregation processes in solvent conditions above a critical water content. Evidence such as an additional absorption band, Beers law deviation, kinetic behavior, and other experimental results obtained from temperature variation and surfactant addition demonstrated the presence of several types of DPH aggregates. Resonance light scattering measurements proved that the aggregate grew in water-rich media by a self-catalyzed process.

Chemometry in undergraduate chemistry courses: a proposal for the use of multivariate analysis in the determination of pKª

An experiment was proposed applying the Chemometric approach of Multivariate Analysis for inclusion in undergraduate Chemistry courses to promote and expand the use of this analytical-statistical tool. The experiment entails the determination of the acid dissociation constant of dyes via UV-Vis electronic spectrophotometry. The dyes used show from simple equilibrium to very complex systems involving up to four protolytic species with high spectral overlap. The Chemometric methodology was more efficient than univariate methods. For use in classes, it is up to the teacher to decide which systems should be utilized given the time constraints and laboratory conditions.

New insights about the self-aggregation of benzoporphyrin derivatives: A theoretical and experimental investigation

The self-aggregation process and its overcoming remain a barrier for the employment of many molecules as photosensitizers (PS) in photodynamic therapy (PDT). The B-ring isomer co-produced during the synthesis of the Verteporfin® (A-ring) is an example. Although both isomers possess similar in vitro/in vivo efficiency, the strong and not well-understood self-aggregation process of the B-ring derivative impairs its clinical use. This paper reports the use of theoretical calculus and its correlation with experimental analysis to find the main differences between the A and B-ring isomers. For that purpose, micelles of Pluronic® P-123 and Sodium Dodecyl Sulfate were chosen as simple membrane models and possible drug delivery system, as in the case of P-123. At physiological pH, the main reason for the high self-aggregation tendency is associated with the higher (22%) molecular volume of the B ring, which increases the van der Waals interactions. However, at mildly acidic conditions, the B ring possesses a shal...