Pluronic® F127 Thermoresponsive Viscum album Hydrogel: Physicochemical Features and Cellular In Vitro Evaluation.

Viscum album L., popularly known as mistletoe, is well known for its anti-cancer properties, and the pharmaceutical application of hydroalcoholic dry extracts is still limited due to its low solubility in aqueous media, and physicochemical instability. The Pluronic® F127 is an amphiphilic polymer, which permits the solubilization of lipophilic and hydrophilic compounds. In this investigation, physicochemical features of hydrogel containing V. album dry extract (VADE-loaded-hydrogel) were performed by: dynamic light scattering (DLS), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and transmission electron microscopy (TEM). VADE-loaded-hydrogel presented nanometer-size micelles with volume distribution ranging from 10.58 nm to 246.7 nm, and a polydispersity index of 0.441. The sample thermal analyses (TG and DSC) showed similar decomposition curves; however, the thermal events indicated an increase in thermal stability in relation to the presence of the extract. In addition to these interesting pharmaceutical features, IC50 values of 333.40 µg/mL and >1000 µg/mL were obtained when tumor (SCC-25) and non-tumor (L929) cells were incubated with VADE-loaded-hydrogel, respectively. The optical and ultrastructural cellular analysis confirmed the tumor selectivity since the following alterations were detected only in SCC-25 cells: disorganization of plasmatic membrane; an increase of cytoplasmatic vacuole size; alteration in the cristae mitochondrial shape; and generation of amorphous cellular material. These results emphasize the promising antitumoral potential of VADE-loaded-hydrogel as an herbal drug delivery system via in vitro assays.

Multiple Response Optimization of Beeswax-Based Nanostructured Lipid Carriers for the Controlled Release of Vitamin E.

Consumer demand for cosmetics is growing, causing a need to develop new systems to release active ingredients. Among these, nanostructured lipid carriers (NLCs) have certain advantages regarding penetration of active compounds in the skin. The study reported here aimed to develop an NLC system for controlled release of vitamin E, a substance that has antioxidant and photoprotective properties. The NLCs containing vitamin E (NLC-VE) were prepared by the melting-emulsionsolidification method, using beeswax as the solid lipid, medium-chain triglycerides (MCTs), coconut oil or avocado oil as liquid lipids and three different nonionic surfactants. The composition of the system was defined by studying the effect of various experimental factors on the size distribution, average diameter and physical stability of the nanoparticles. The optimization of these characteristics, achieved by a Box-Behnken statistical design, showed that 8% w/w of the nonionic surfactant Tween 80, 24% ultrasound amplitude and processing time of 2 minutes and 16 seconds generated nanoparticles with homogeneous size (PDI = 0.11±0.02), average diameter of 180±20 nm and physical stability of 12 weeks. The NLC-VE systems prepared under the optimal conditions, containing Tween 80, beeswax and MCTs, were formulated as viscous suspensions by adding Pluronic F-127, a poly(ethylene oxide)-poly(propylene oxide) block copolymer, at a concentration of 10% w/w. The colloidal nanosuspension obtained had a viscosity of 222 mPa·s and released 70% of the active substance in 6 hours, indicating it is a promising candidate for controlled release of vitamin E.

Nanovesicle-based formulations for photoprotection: a safety and efficacy approach.

Vesicular nanosystems are versatile and they are able to encapsulate actives with different solubilities, such as lipophilic and hydrophilic compounds. The most well-known vesicular nanosystems are liposomes and niosomes, the last one is formed by non-ionic surfactants. In the present work, we developed photoprotective niosomes containing sunscreens (octyl methoxycinnamate, diethylamino hydroxybenzoyl hexyl benzoate and phenylbenzimidazole sulfonic acid), non-ionic surfactants, cholesterol and stearylamine (positive-charged lipid). Studies based on dynamic light scattering techniques, entrapment efficiency and morphology by transmission electron microscopy were performed to characterize the niosomes. In addition, rheology, pH, in vitro sun protection factor (SPF) efficacy and toxicity and in vivo and in vitro safety were determined for the niosome formulations F-N1 and F-N2. The mean sizes of N1 and N2 were 168 ± 5 nm and 192 ± 8 nm, respectively, and their morphologies were spherical, unilamellar and with an entrapment efficiency of more than 45% for each sunscreen. Both formulations, F-N1 and F-N2 presented characteristics of pseudoplastic non-Newtonian fluids, showing declining viscosity with increasing shear rate applied. SPF values were considered satisfactory, 34 ± 8 for formulation F-N1 and 34 ± 5 for F-N2. The formulations did not present toxicity when tested in macrophages and the pH was compatible with skin, which minimizes allergies. The in vitro safety assay showed lipophilic sunscreens greater affinity for the epidermis, since this layer contains natural lipids. In vivo safety assay suggests that the increased skin retention of N2 is directly correlated with the positive charge of stearylamine. Stable photoprotective niosomes were obtained and were shown to be promising nanostructures to be used against solar radiation.

Polymeric Nanostructured Systems for Liquid Formulation of Praziquan-tel: Development and in vitro Assessment.

Praziquantel (PZQ) is widely used in the treatment of several parasitic infections in both humans and animals, and is the first choice in the treatment of Schistosomiasis in humans. However, PZQ is a hydrophobic drug, and its low aqueous solubility has been a significant barrier to the development of oral liquid formulations that may provide improved bioavailability, pharmacokinetic profile, and compliance. The aim of this study was thus (i) to develop an oil-in-water (O/W) nanoemulsion(NE)-based platform for the delivery of PZQ in liquid form; (ii) to study the transport of PZQ formulated in NEs across an in vitro model of the intestinal epithelium; and (iii) to determine the toxicity profile of the NEs and their individual components on the model epithelium. We also sought to compare the toxicity and transport profiles of the proposed formulations, with those of PZQ in a solid nanostructured particle system - PZQ encapsulated within poly(lactic acid-co-glycolic acid) (PLGA) nanoparticles (NPs). Two essential oils were selected as the oil phase in the NEs, namely clove and orange. The NEs were prepared with selected non-ionic surfactants and had high solubilization capacity towards PZQ, and average diameters well below 100nm. The NEs also showed long term physical stability at both simulated physiological and gastric conditions. NEs with clove oil (NEC-PZQ) were observed to have a lower cytotoxic profile when compared to the orange oil NEs (NEO-PZQ). The results also showed that the transport of PZQ formulated within such nanostructured systems was much greater and larger rates across confluent and polarized Caco-2 monolayers when compared to free PZQ. Interestingly, little difference in PZQ transport between the NEs and NPs was observed. These results point to NEs as potentially viable strategies for the liquid formulation of PZQ in particular, and more broadly to the formulation of other hydrophobic therapeutics that may be employed in the fight against important neglected diseases such as Schistosomiasis, which alone affects more than 240 million people worldwide.

Nanoemulsions as delivery systems for lipophilic drugs.

Nanoemulsions have received a growing attention as colloidal drug carriers for pharmaceutical applications. Their advantages over conventional formulations include drug enhanced solubility and bioavailability, protection from toxicity, improved pharmacological activity and stability, more sustained delivery and protection from physical and chemical degradation. Nanoemulsions can be prepared by two major techniques, high-energy and low-energy emulsification. Both these emulsification methods have proved to be efficient to obtain stable nanoemulsions with small and highly uniform droplets. Further research into nanoemulsions is important to develop novel liquid formulations with more efficient results in therapeutic.