Meglumine-based supra-amphiphile self-assembled in water as a skin drug delivery system: Influence of unfrozen bound water in the system bioadhesiveness.

Hexagonal liquid crystals and supramolecular polymers from meglumine-based supra-amphiphiles were developed as drug delivery systems to be applied on the skin. The influence of fatty acid unsaturation on the structure and mechanical properties was evaluated. Moreover, we have investigated the system biocompatibility and how the type of water could influence its bioadhesive properties. Meglumine-oleic acid (MEG-OA) was arranged as hexagonal liquid crystals at 30-70 wt% water content, probably due to its curvature and increased water solubility. Meglumine-stearic acid (MEG-SA) at 10-80 wt% water content self-assembled as a lamellar polymeric network, which can be explained by the low mobility of MEG-SA in water due to hydrophobic interactions between fatty acid chains and H-bonds between meglumine and water molecules. Both systems have shown suitable mechanical parameters and biocompatibility, making them potential candidates to encapsulate therapeutic molecules for skin delivery. Moreover, a strong positive correlation between the amount of unfrozen bound water in meglumine-based systems and the bioadhesion properties was observed. This work shows that a better understanding of the physicochemical properties of a drug delivery system is extremely important for the correlation with the desired biological response and, thus, improve the product performance for biomedical applications.

Synthesis of functionalized mesoporous material from rice husk ash and its application in the removal of the polycyclic aromatic hydrocarbons.

The rice husk ash (RHA) was used as an alternative source of silica for the synthesis of the functionalized mesoporous material, which was used in the removal of the PAHs naphthalene (Nap), benzo[b]fluoranthene (B[b]F), benzo[k]fluoranthene (B[k]F), and benzo[a]pyrene (B[a]P) from aqueous media. The PABA-MCM-41 (RHA) was characterized using FTIR, TGA, SAXS, and N2 adsorption-desorption analyses. Removal experiments were performed to determine the initial concentrations, individual adsorption in comparison with the mixture of the PAHs, PABA-MCM-41 (RHA) amount, pH, time, and temperature, and the results obtained were statistically analyzed. The PABA-MCM-41 (RHA) presented the SBET, VT, and DBJH values of 438 m2 g-1, 0.41 cm3 g-1, and 3.59 nm, respectively, and good thermal stability. The qe values found in the kinetic equilibrium for the PAHs mixture followed increasing order: Nap < B[a] P < B[k]F < B[b]F, with removal percentages of 89.08 ± 0.00, 93.85 ± 0.28, 94.54 ± 0.10, and 97.80 ± 0.05%, respectively. Graphical abstract.

Anti-hyperalgesic and anti-inflammatory effects of citral with ß-cyclodextrin and hydroxypropyl-ß-cyclodextrin inclusion complexes in animal models.

Citral (CIT) is a monoterpene formed by the geranial and neral stereoisomers. CIT is the major compound of Cymbopogon citratus essential oil, commonly known as "lemongrass", and has demonstrated potential antihyperalgesic, anti-nociceptive and anti-inflammatory effects. However, CIT shows high volatility, low solubility in water and consequent low bioavailability, which limits its use. Therefore, the aim of this study was to evaluate cell viability, anti-hyperalgesic and anti-inflammatory effects of inclusion complexes of CIT on ß-cyclodextrin (ß-CD) and hydroxypropyl-ß-cyclodextrin (HP-ß-CD). Initially, physical mixture (PM) and freeze-dried inclusion (FD) complexes of CIT/ß-CD and CIT/HP-ß-CD were obtained in the molar ratio (1:1). The samples were characterized by DSC, TG/DTG, FT-IR, XRD, SEM and the complexation efficiency were performed by HPLC. Cell viability assay was performed by rezasurin reduction technique in J774 macrophages cell line. The motor activity through rota rod apparatus, mechanical hyperalgesia and pleurisy induced by carrageenan were evaluated in mice. The complexation of CIT was evidenced with ß-CD and HP-ß-CD by the characterization techniques analyzed. The complexation efficiency of CIT/ß-CD and CIT/HP-ß-CD were 78.6% and 71.7%, respectively. The CIT, CIT/ß-CD and CIT/HP-ß-CD showed cell viability in macrophages and did not interfere in the motor activity of mice. Besides that, the samples demonstrated antihyperalgesic and anti-inflammatory activity due to the reduction in total leukocytes and TNF-α levels. However, CIT/ß-CD has better pharmacological effects among the three samples evaluated. Therefore, CIT/ß-CD has potential for the development of products to treat inflammatory and pain reactions.

Tailoring microstructural, drug release properties, and antichagasic efficacy of biocompatible oil-in-water benznidazol-loaded nanoemulsions.

This study explored the transition of lamellar-type liquid crystal (LLC) to biocompatible oil-in-water nanoemulsions able to modify benznidazole (BNZ) release and target the drug to cells infected with the T. cruzi parasite. Three cosolvents (2methylpyrrolidone [NMP], polyethylene glycol [POL], and propylene glycol [PRO] were tested to induce the transition of anisotropic LLC systems to isotropic nanoemulsions. Mixtures of soy phosphatidylcholine with sodium oleate stabilized the dispersions of medium chain triglyceride in water. Rheological measurements, polarized microscopy, and small angle X-ray scattering demonstrated that there is a phase transition from LLC to desired nanoemulsions. These small and narrow droplet-sized nanocarriers exhibited some advantages and promising features, such as the enhanced BNZ aqueous solubility and slow drug release rate. In vitro cell biocompatibility of formulations was assessed in the Vero E6 and SiHa cell lines. Drug-loaded nanoemulsions inhibited the epimastigote growth of the T. cruzi parasite (IC50 0.208 ±â€¯0.052 µg mL-1) and reduced its infective life form trypomastigote (IC50 0.392 ±â€¯0.107 µg mL-1). The oil-in-water nanoemulsions were demonstrated as promising biocompatible liquid drug delivery systems capable of improving the BNZ trypanocidal activity for the treatment of Chagas disease.

Phase Transitions of Isotropic to Anisotropic Biocompatible Lipid-Based Drug Delivery Systems Overcoming Insoluble Benznidazole Loading.

Previous studies reported low benznidazole (BNZ) loading in conventional emulsions due to the weak interaction of the drug with the most common oils used to produce foods or pharmaceuticals. In this study, we focused on how the type of surfactant, surfactant-to-oil ratio w/w (SOR) and oil-to-water ratio w/w (OWR) change the phase behavior of different lipid-based drug delivery systems (LBDDS) produced by emulsion phase inversion. The surfactant mixture composed of soy phosphatidylcholine and sodium oleate (1:7, w/w, hydrophilic lipophilic balance = 16) stabilized medium chain triglyceride in water. Ten formulations with the clear aspect or less turbid dispersions (five with the SOR ranging from 0.5 to 2.5 and five with the OWR from 0.06 to 0.4) were selected from the phase behavior diagram to assess structural features and drug-loading capacity. The rise in the SOR induced the formation of distinct lipid-based drug delivery systems (nanoemulsions and liquid crystal lamellar type) that were identified using rheological measurements and cross-polarized light microscopy images. Clear dispersions of small and narrow droplet-sized liquid-like nanoemulsions, Newtonian flow-type, were produced at SOR from 0.5 to 1.5 and OWR from 0.12 to 0.4, while clear liquid or gel-like liquid crystals were produced at SOR from 1.5 to 2.5. The BNZ loading was improved according to the composition and type of LBDDS produced, suggesting possible drug location among surfactant layers. The cell viability assays proved the biocompatibility for all of the prepared nanoemulsions at SOR less than 1.5 and liquid crystals at SOR less than 2.5, demonstrating their promising features for the oral or parenteral colloidal delivery systems containing benznidazole for Chagas disease treatment.

The Monoglyceride Content Affects the Self-Assembly Behavior, Rheological Properties, Syringeability, and Mucoadhesion of In Situ-Gelling Liquid Crystalline Phase.

This article reports the development of a precursor liquid crystalline system based on a mixture of monoglycerides (MO) and Cremophor(®) (CREM) that exhibits in situ gelation to a liquid crystalline phase. The effects of different MO/CREM ratios and the water content (WC) on several performance characteristics were investigated with a full factorial design. The formulations were characterized by polarized light microscopy, small-angle X-ray scattering, and water uptake assays. Rheological, syringeability, and mucoadhesion evaluation were also performed. The polarized light microscopy and small-angle X-ray scattering results for average and high MO/CREM ratios (2.1 and 4.0, respectively) indicated the coexistence of phases in transition to the liquid crystalline phase, independently of the WC. These systems became more viscous after taking up water, showing peaks characteristic of a cubic phase. Systems that had average and high MO/CREM ratios also exhibited shear-thinning behavior and high elasticity. Most systems showed suitable mucoadhesion for buccal purposes. Response surface methodology results demonstrated that the relative contribution of MO was the principal factor that affected the performance of the system. Accordingly, these precursor systems with average to high MO/CREM ratios and an average WC (10% w/w) demonstrated physicochemical and mucoadhesive properties that could enable them to be used as an in situ-gelling controlled drug delivery platform.

Rheological Characterization and Safety Evaluation of Non-Ionic Lamellar Liquid Crystalline Systems Containing Retinyl Palmitate.

Retinyl palmitate (RP) is widely used as a special interest ingredient in dermatological formulations to improve the elasticity of the skin and to reduce wrinkles by stimulating collagen synthesis. Nanotechnology-based drug delivery systems, such as liquid crystalline systems (LCSs), can modulate drug permeation into skin and improve the drug action. The effects of such systems on the skin, however, are not completely known. Possible undesirable effects of these formulations on the skin can be detected and interpreted by histopathology and histomorphometry. The objective of this study was to perform a rheological characterization to evaluate the safety of RP used in a lamellar LCS in vitro and in vivo. LCSs containing polyether functional siloxane as a surfactant, silicon glycol copolymer as an oil phase and water at ratios of 60:10:30 and 40:30:30, with (F1v and F2v, respectively) and without (F1 and F2 respectively) RP, were investigated. The rheological characterization was performed using steady shear rate sweep tests and dynamic frequency sweep tests carried out for up to 30 days for various storage temperature conditions (25 ± 2 °C, 37 ± 2 °C and 5 ± 2 °C). Cytotoxic effects were evaluated using J-774 mouse macrophages as a cellular model system. The in vivo tests were conducted on rabbits that had areas of skin treated as follows for 15 days: C (Control); F1; F1v; F2; and F2v. Histomorphometric and histopathological techniques were used to estimate the thicknesses of the epidermis and stratum corneum and the numbers of fibroblasts and leukocytes in the papillary dermis. Mean values were compared by ANOVA, followed by the Tukey test (p < 0.05). The steady shear rate sweep and dynamic frequency sweep tests confirmed the high viscosity of the LCS and the typical pseudo-plastic characteristic of the lamellar system. The RP-unloaded LCS and the RP-loaded LCS did not produce cytotoxicity, nor did they provoke significant thickening of the epidermis and stratum corneum. The number of leukocytes in the treated areas did not change; however, the number of fibroblasts in the area treated with F1v was higher than in the areas treated with the control and F2. The histological analyses demonstrated that none of the formulations irritated the skin and that formulation F1v significantly increased the number of fibroblasts in the dermis, which could result in an increase in the production of collagen.

Development and in vitro evaluation of surfactant systems for controlled release of zidovudine.

The development of a controlled-release dosage form of zidovudine (AZT) is of crucial importance, in view of the pharmacokinetics of its toxic activity. A suitable drug delivery system could increase AZT bioavailability, reducing its dose-dependent side effects. In this study, systems composed of polyoxypropylene (5) polyoxyethylene (20) cetyl alcohol as surfactant (S), oleic acid as oil phase (O), and water (W) were developed, as possible AZT control release systems. They were characterized by polarized light microscopy (PLM), SAXS, and rheological analysis, followed by in vitro release assay. PLM and SAXS results indicated that the mixtures of S/O/W in the proportions 55/35/10 and 55/25/20 formed microemulsion (ME) systems, while 55/20/25 formed lamellar phase. The incorporation of AZT in these systems was greater than in water or oil; moreover, AZT incorporation did not significantly change the phase behavior of the mixtures. MEs behave as Newtonian fluids in flow rheological analysis and the lamellar phase as a pseudoplastic fluid. The release profile indicated that AZT could be released in a controlled manner, since an exponential pattern governs AZT diffusion, as demonstrated by the Weibull mathematical model. These systems are potential carriers for AZT and could have advantages over conventional pharmaceutical forms.