Ana Amélia Moreira Lira

Estudo de liberação e permeação in vitro do diclofenaco de dietilamônio em microemulsão gel-like

The goal of this study was to produce and characterize a new microemulsion gel-like carrier system (MEG) by using the pseudo-ternary phase-diagram concept. The diclofenac diethylamine (DDA) was incorporated in the MEG and its in vitro release and permeation profiles were performed using Franz-type diffusion cells. The results revealed that the commercial DDA emulgel provided significantly higher Kp of DDA (2.2-fold) as compared to the MEG. Similar data were obtained in the permeation studies in which DDA Kp 4.7-fold higher. Therefore, MEG presents higher potential as a topical delivery system for DDA when compared to the commercial DDA emulgel.

Compatibility study of hydroxypropylmethylcellulose films containing zidovudine and lamivudine using thermal analysis and infrared spectroscopy

Zidovudine (AZT) and lamivudine (3TC) are drugs commonly used in the treatment of acquired immune deficiency syndrome; however, these drugs have low bioavailability and short biological half-life. These factors contribute to the emergence of various side effects and lack of patient adherence to treatment. Therefore, the study of drug delivery systems is of extreme interest. In this context, this study intends to develop hydroxypropylmethylcellulose films (HPMC) containing AZT and films containing 3TC, and assess the existence of drug/polymer interactions by means of thermal analysis techniques [differential scanning calorimetry (DSC) and thermogravimetry (TG)/derivative TG (DTG)], Fourier transform infrared (FTIR) spectroscopy, and X-ray diffraction (XRD), contributing to the optimization of antiretroviral therapy. The films produced showed drying uniformity and drug distribution. DSC curves indicated that these drugs may be in an amorphous form dispersed in the polymeric matrix. Thermal decomposition profiles obtained in the TG/DTG studies of films containing drugs showed similarities with the curves of their respective physical mixtures. The FTIR spectra showed the characteristic bands conservation of AZT and 3TC isolated in the films with drugs. The results indicate that these drugs did not undergo a process of degradation or chemical interaction with the polymer that would lead to the modification or alteration of their chemical structures. XRD studies confirmed that these drugs were homogenously dispersed in the polymeric matrix. These results also showed that there was no drug/polymer incompatibility in HPMC films.

An environmentally safe larvicide against Aedes aegypti based on in situ gelling nanostructured surfactant systems containing an essential oil

HYPOTHESIS Liquid crystalline precursors, which are in situ gelling nanostructured surfactant systems, can undergo phase transition in aqueous solution and become more structured aggregates, controlling release of larvicides and acting as biotechnology alternatives for dengue control. Such systems can contain bioactive substances as Citrus sinensis essential oil (CSEO) which exhibits biological activity against Aedes aegypti (Ae. aegypti) larvae. EXPERIMENTS The formulations were composed by fixed concentration of CSEO stabilized by Polyoxypropylene (5) Polyoxyethylene (20) Cetyl Ether (PPG-5 CETETH-20): oleic acid (OA) 2:1, increasing water content. The phase diagram was established and systems structure was evaluated by polarized light microscopy (PLM), small angle X-ray scattering (SAXS) and rheology. Median lethal concentration was determined against Ae. aegypti larvae. FINDINGS The phase diagram exhibited four regions: liquid crystal (LC), emulsion, microemulsion (ME) and phase separation. The PLM and SAXS distinguished microemulsions, lamellar and hexagonal LC structures. Flow and oscillatory tests showed that increasing water content increases elasticity from Newtonian to non-newtonian behavior confirming the in situ gelation behavior. The larvicidal activity of formulations indicates that these nanostructured systems improved the oil solubility in aqueous medium and in addition are potential environmental larvicide against Ae. aegypti larvae.

Microemulsion Formulations for the Transdermal Delivery of Lapachol

This project was carried out to investigate the feasibility of using microemulsions for transdermal delivery of lapachol. From the screening of surfactants and oils, a range of microemulsions were developed using oleic acid, a mixture of Cremophor EL and Tween 20 and water. The solubility of lapachol was determined in these ingredients and in the formulated microemulsions. The microemulsions were characterised using cross-polarising light microscopy, their electrical conductivity, pH, zeta potential and rheology were analysed, and they were also investigated using small-angle X-ray scattering and differential scanning calorimetry. Ex vivo studies were performed using porcine ear skin and Franz diffusion cells to investigate the permeation and retention of lapachol. Systems containing different concentrations of Cremophor EL (8.4–41.6%), Tween 20 (5.4–41.6%) and oleic acid (12–31.9%) are able to form microemulsions. Lapachol was delivered more effectively through the skin from all of the microemulsions tested than by the control (oleic acid). These studies indicated that microemulsions incorporating lapachol were formed successfully and that these enhanced drug delivery and retention in the skin. Microemulsion systems may, therefore, provide promising vehicles for percutaneous delivery of lapachol.

Effect of Ouratea sp. butter in the crystallinity of solid lipids used in nanostructured lipid carriers (NLCs)

The aim of this work was to evaluate the effect of Ouratea sp. butter (OB) on crystallinity of solid lipids used in nanostructured lipid carriers systems. Firstly, the composition of fatty acids in OB was evaluated by transesterification reaction for gas chromatography fatty acid methyl ester analysis. The solid lipids such as stearic acid (SA), beeswax (BW) and carnauba wax (CW) were submitted to recrystallization process (heating–cooling). Moreover, binary mixtures between solid lipids and OB were prepared in ratio 1:1 (w/w) by heating of the components above the melting point followed by cooling at room temperature. Thus, the samples were characterized by differential scanning calorimetry (DSC), thermogravimetry (TG), X ray diffraction (XRD) and hot-stage polarized optical microscopy (HSPOM). DSC curves showed a shift of the melting point to lower temperatures in the lipid mixtures with OB. TG data suggested a thermal stability reduction in the lipid mixtures containing SA and CW and an increase thermal stability in the mixture containing BW. XRD data confirmed DSC results, showing a reduction in intensity of main diffraction peaks of the lipid mixtures and a presence of the amorphous portion in angle 2θ: 22°. Finally, HSPOM demonstrated that the microstructures of solid lipids decreased in size and thickness in the mixtures containing OB at room temperature and slightly before the melting point, confirming previous characterizations. These results suggest that lipid mixtures with OB present a lower crystallinity, and it is expected that amorphous portion facilitates drug incorporation, for example.

Desenvolvimento e validação de método analítico em CLAE-UV para a quantificação de ácido retinóico em microcápsulas de alginato e quitosana

Retinoic acid (RA) has been used in the treatment of severe acne, wrinkles and cellulite. However, it induces skin irritation and rapidly suffers degradation under light and high temperate exposure. Rapid analytical methods to quantify retinoic acid are therefore mandatory for in vitro drug release studies. In this framework, the aim of this study was to develop and validate a rapid and responsive method to quantify the RA in microcapsules of chitosan and alginate containing babassu oil dispersed in natrosol® hydrogel using high performance liquid chromatography (HPLC). Furthermore this method was used to quantify in vitro release kinetics of RA from microcapsules. The analyses have been carried through an isocratic HPLC-UV method using a reversed phase 150 x 4.6 mm C18 (5μm) column, a mobile phase constituted of methanol and 1% acetic acid (85:15) at a flow rate of 1.8 mL/min and detection at 350 nm. The linearity range was 0.5-60 μg/mL (r2 = 0.999). The validated HPLC-UV method was responsive, specific, accurate, precise, and economic and the RA retention time was 5.8 ± 0.4 minutes, being therefore, faster than that previously reported.

Skin permeation, biocompatibility and antitumor effect of chloroaluminum phthalocyanine associated to oleic acid in lipid nanoparticles

The objective of this study was to develop and characterize lipid nanoparticles (LNs) containing chloroaluminum phthalocyanine (ClAlPc) to reduce the aggregation of the drug and improve its skin penetration and its antitumor effect. LNs were prepared and characterized by using stearic acid (SA) as solid lipid and oleic acid (OA) as liquid lipid in different proportions. in vitro and in vivo skin penetration was evaluated using modified Franz diffusion cells and fluorescence microscopy, respectively. in vitro biocompatibility and Photodynamic Therapy (PDT) were performed using L929-fibroblasts cell line and A549 cancer cell line and melanoma BF16-F10, respectively. OA promoted the increase in the encapsulation efficiency and drug loading, reaching values of 95.8% and 4%, respectively. The formulation with 40% OA (NLC 40) showed a significantly higher (p < 0.01) amount of drug retained in the skin compared to other formulations. All formulations developed were considered biocompatible. PDT evidenced the antitumor efficacy of NLC 40 with reduced cell viability for approximately 10% of cancer cells, demonstrating that the presence of OA in the NLC seems to potentialize this antitumor effect. PDT in BF16-F10 melanoma using NLC 40 resulted in a reduction in mean cell viability of approximately 99%. According to the results obtained, the systems developed may be promising for the incorporation of ClAlPc in the treatment of skin cancer by photodynamic therapy.

Chitosan/pvp-based mucoadhesive membranes as a promising delivery system of betamethasone-17-valerate for aphthous stomatitis

Mucoadhesive membranes were proposed in this study as drug delivery system for betamethasone-17-valerate (BMV) in the treatment of recurrent aphthous stomatitis (RAS). The membranes were obtained by using the polymers chitosan (CHI) in both presence and absence of polyvinilpyrrolidone (PVP), following the solvent evaporation method. The presence of PVP in the membranes causes significant modifications in its thermal properties. Changes in the thermal events at 114 and 193 °C (related to BMV melting point), and losses in mass (39.38 and 30.68% for CH:PVP and CH:PVP-B, respectively), suggests the incorporation of BMV in these membranes. However, the morphological aspects of the membranes do not change after adding PVP and BMV. PVP causes changes in swelling ratios (>80%) of the membranes, and it is suggested that the reorganization of the polymer mesh was highlighted by the chemical interactions between the polymers leading to different percentages of BMV released ∼40% and ∼80% from CH-B and CH:PVP-B. BMV release profile follows Korsmeyer and Peppas model (n > 0.89) which suggests that the diffusion of the drug in the swollen matrix is driven by polymer relaxation. In addition, the membranes containing PVP (higher swelling ability) present high rates of tensile strength, and therefore, higher mucoadhesion. Moreover, given the results presented, the developed mucoadhesive membranes are a promising system to deliver BMV for the treatment of RAS.

Third-Generation Transdermal Delivery Systems Containing Zidovudine: Effect of the Combination of Different Chemical Enhancers and a Microemulsion System

ABSTRACTThis study aimed to examine the influence of the combination of chemical enhancers and a microemulsion on the transdermal permeation of zidovudine (AZT). Ethanol, 1,8-cineole, and geraniol were incorporated in a microemulsion. The droplet size, zeta potential, rheology, and SAXS analysis were performed. The permeation enhancer effect was evaluated using pig ear skin. Snake skin (Boa constrictor) treated with the formulations was also used as a stratum corneum model and studied by attenuated total reflectance-infrared spectroscopy. As a result, it was observed that the incorporation of the chemical enhancers promoted a decrease of the droplet size and some rheological modifications. The 1,8-cineole associated with the microemulsion significantly increased the permeated amount of AZT. Conversely, ethanol significantly increased the quantity of the drug retained in the skin. The probable mechanism for the cineole and ethanol effects was respectively: fluidization and increasing of the diffusion coefficient, and increasing of the partition coefficient. Surprising, geraniol + microemulsion drastically decreased both the permeated and the retained amount of AZT into the skin. Thus, the adequate association of microemulsion and chemical enhancers showed to be a crucial step to enable the topical or transdermal use of drugs.