Pluronic® triblock copolymer-based nanoformulations for cancer therapy: A 10-year overview.

This paper provides a review of the literature on the use of Pluronic® triblock copolymers for drug encapsulation over the last 10 years. A special focus is given to the progress of drug delivery systems (e.g., micelles, liposomes, micro/nanoemulsions, hydrogels and nanogels, and polymersomes and niosomes); the beneficial aspects of Pluronic® triblock copolymers as biological response modifiers and as pharmaceutical additives, adjuvants, and stabilizers, are also discussed. The advantages and limitations encountered in developing site-specific targeting approaches based on Pluronic-based nanostructures in cancer treatment are highlighted, in addition to innovative examples for improving tumor cytotoxicity while reducing side effects.

Correction: Diniz et al. Silver Nanoparticles-Composing Alginate/Gelatine Hydrogel Improves Wound Healing In Vivo. Nanomaterials 2020, 10, 390.

In the original publication, there was a mistake in Figure 6 as published [...].

New Trends in Drug Delivery Systems for Veterinary Applications.

BACKGROUND: The veterinary pharmaceutical industry has shown significant growth in recent decades. Several factors contribute to this increase as the demand for the improvement of the quality of life of both domestic and wild animals, together with the need to improve the quality, productivity, and safety of foodstuffs of animal origin. METHODS: The goal of this work was to identify the most suitable medicines for animals that focus on drug delivery routes as those for humans, although they may have different devices, such as collars and ear tags. RESULTS: Recent advances in drug delivery systems for veterinary use are discussed, both from academic research and the global market. The administration routes commonly used for veterinary medicines are also explored, while special attention is given to the latest technological trends to improve the drug performance, reducing the number of doses, animal stress, and side effects. CONCLUSION: Drug delivery system in veterinary decreased the number of doses, side effects, and animal stress that are a small fraction of the benefits of veterinary drug delivery systems and represent a significant increase in profit for the industry; also, it demands investments in research regarding the quality, safety, and efficacy of the drug and the drug delivery systems.

Otoliths-composed gelatin/sodium alginate scaffolds for bone regeneration.

Evidence that otoliths, mineral-rich limestone concrescences present in the inner ear of bone fishes, can accelerate bone formation in vivo has been previously reported. The goal of this work was the development, characterization, and evaluation of the cytocompatibility of otoliths-incorporated sodium alginate and gelatin scaffolds. Cynoscion acoupa-derived otoliths were characterized by X-ray fluorescence spectrometry (FRX), particle size, free lime, and weight loss by calcination. Furthermore, otoliths were incorporated into sodium alginate (ALG/OTL-s) or gelatin (GEL/OTL-s) scaffolds, previously developed by freeze-drying. Then, the scaffolds were characterized by thermogravimetric analysis (TGA/DTG), differential scanning calorimetry (DSC), infrared spectroscopy with Fourier transform (FTIR), swelling tests, and scanning electron microscopy (SEM). Cytotoxicity assays were run against J774.G8 macrophages and MC3T3-E1 osteoblasts. Data obtained from TGA/DTG, DSC, and FTIR analyses confirmed the interaction between otoliths and the polymeric scaffolds. SEM showed the homogeneous porous 3D structure rich in otolith micro-fragments in both scaffolds. Swelling of the GEL/OTL-s (63.54 ± 3.0%) was greater than of ALG/OTL-s (13.36 ± 9.9%) (p < 0.001). The viability of J774.G8 macrophages treated with both scaffolds was statistically similar to the group treated with DMEM only (p > 0.05) and significantly higher than that treated with Triton-X (p < 0.01) at 72 h. Both scaffolds showed approximately 100% growth of MC3T3-E1 osteoblasts by 24 h, similarly to control (p > 0.05). However, by 48 h, only ALG/OTL-s showed growth similar to control (p > 0.05), whereas GEL/OTL showed a significantly lower growth index (p < 0.05). In conclusion, the physicochemical profiles suggest proper interaction between the otoliths and the two developed polymeric 3D scaffolds. Moreover, both materials showed cytocompatibility with J774.G8 macrophages but the growth of MC3T3-E1 osteoblasts was higher when exposed to ALG/OTL-s. These data suggest that sodium alginate/otoliths scaffolds are potential biomaterials to be used in bone regeneration applications. Graphical abstract.

Brazilian Red Propolis: Extracts Production, Physicochemical Characterization, and Cytotoxicity Profile for Antitumor Activity.

Brazilian red propolis has been proposed as a new source of compounds with cytotoxic activity. Red propolis is a resinous material of vegetal origin, synthesized from the bees of the Appis mellifera family, with recognized biological properties. To obtain actives of low polarity and high cytotoxic profile from red propolis, in this work, we proposed a new solvent accelerated extraction method. A complete 23 factorial design was carried out to evaluate the influence of the independent variables or factors (e.g., temperature, number of cycles, and extraction time) on the dependent variable or response (i.e., yield of production). The extracts were analyzed by gas chromatography coupled with mass spectrometry for the identification of chemical compounds. Gas chromatography analysis revealed the presence of hydrocarbons, alcohols, ketones, ethers, and terpenes, such as lupeol, lupenone, and lupeol acetate, in most of the obtained extracts. To evaluate the cytotoxicity profile of the obtained bioactives, the 3-(4,5-dimethyl-2-thiazole)-2,5-diphenyl-2-H-tetrazolium bromide colorimetric assay was performed in different tumor cell lines (HCT116 and PC3). The results show that the extract obtained from 70 °C and one cycle of extraction of 10 min exhibited the highest cytotoxic activity against the tested cell lines. The highest yield, however, did not indicate the highest cytotoxic activity, but the optimal extraction conditions were indeed dependent on the temperature (i.e., 70 °C).

Rosemary (Rosmarinus officinalis L., syn Salvia rosmarinus Spenn.) and Its Topical Applications: A Review.

Topical application is an important administration route for drugs requiring local action on the skin, thereby avoiding their systemic absorption and adverse side effects. Rosmarinus officinalis L. (syn. Salvia rosmarinus Spenn.), popularly known as rosemary, is an aromatic plant with needle-like leaves belonging to the Lamiaceae family. Rosemary has therapeutic properties and has been used in the folk medicine, pharmaceutical, and cosmetics industries, mainly for its antioxidant and anti-inflammatory properties, which are attributed to the presence of carnosol/carnosic and ursolic acids. The therapeutic use of rosemary has been explored for the treatment of inflammatory diseases; however, other uses have been studied, such as wound healing and skin cancer and mycoses treatments, among others. Besides it therapeutic uses, rosemary has potential applications in cosmetic formulations and in the treatment of pathological and non-pathological conditions, such as cellulite, alopecia, ultraviolet damage, and aging. This review aims to critically discuss the topical applications of rosemary found in the literature while also offering relevant information for the development of topical formulations of its bioactive compounds.

Evaluation of In Vitro Solar Protection Factor (SPF), Antioxidant Activity, and Cell Viability of Mixed Vegetable Extracts from Dirmophandra mollis Benth, Ginkgo biloba L., Ruta graveolens L., and Vitis vinífera L.

The aim of this study was to validate a HPLC method for the assay of flavonoids in extracts obtained from natural sources, i.e., from Dirmophandra mollis Benth, Ginkgo biloba L., Ruta graveolens L., and Vitis vinífera L. The potential sun protecting effect, antioxidant activity, and cell viability of the extracts were also determined. Individual extracts (obtained from each individual species) and a mixed extract (containing the four extracts) were analyzed by the validated HPLC method for the identification of flavonoids and quantification of rutin and quercetin. An in vitro cell viability study was carried out using the neutral red method. The in vitro sun protection factor was determined by spectral transmittance and in vitro antioxidant efficacy was evaluated against DPPH, ABTS, and AAPH radicals. The HPLC method used for the identification and quantification of flavonoids in extracts exhibited linearity, precision, accuracy, and robustness. Detection and quantification limits were, respectively, 2.881 ± 0.9 µg·mL-1 and 0.864 ± 0.9 µg·mL-1 for quercetin, and 30.09 ± 1 µg·mL-1 and 9.027 ± 1.1 µg·mL-1 for rutin. All extracts did not affect cell viability at the evaluated concentration range and exhibited a sun protection effect and antioxidant activity. Among the evaluated extracts, Ginkgo biloba L. and the mixed extract depicted the most expressive antioxidant activity. The mixed extract exhibited sunscreen protection against ultraviolet A (UVA) and ultraviolet B (UVB) and a critical wavelength of 372.7 ± 0.1. Our results translate the enhanced flavonoids' composition of the mixed extract, which may be a potential alternative over sunscreens and antioxidants in pharmaceutic/cosmetic formulations.

Flavonoid-Enriched Plant-Extract-Loaded Emulsion: A Novel Phytocosmetic Sunscreen Formulation with Antioxidant Properties.

The aim of this study was to develop a phytocosmetic sunscreen emulsion with antioxidant effect, containing a blend of flavonoid-enriched plant extracts. In vitro sun protection factor, antioxidant activity, skin irritation, photostability, cutaneous permeation, and retention of flavonoids were evaluated. Thermodynamically stable emulsions were obtained and tested for sensorial analysis after loading the blend of extracts. The selected emulsion was stable when stored at low temperatures (5 C), for which after 120 days the concentration of quercetin and rutin were above their limit of quantification, i.e., 2.8 ± 0.39 µg/mL and 30.39 ± 0.39 µg/mL, respectively. Spreadability, low rupture strength and adhesiveness were shown to be similar to a conventional topical product. Higher brittleness, pseudo-plastic, and viscoelastic behaviors were also recorded for the developed phytocosmetic sunscreen. The product presented a critical wavelength of 387.0 nm and ultraviolet rays A and B (UVA/UVB) rate of 0.78, confirming that the developed formulation shows capacity for UVA/UVB protection, protecting skin against damages caused by Ultraviolet (UV) radiation. Rutin was shown to permeate the skin barrier and was also quantified in the stratum corneum (3.27 ± 1.92 µg/mL) by tape stripping and retention test (114.68 ± 8.70 µg/mL). The developed flavonoid-enriched phytocosmetic was shown to be non-irritant to skin by an in vitro assay. Our results confirm the antioxidant activity, sun protection, and physical properties of the developed phytocosmetic for topical application.

Development, Cytotoxicity and Eye Irritation Profile of a New Sunscreen Formulation Based on Benzophenone-3-poly(ε-caprolactone) Nanocapsules.

The objective of this work was to characterize the toxicological profile of a newly developed sunscreen formulation based on polymeric nanocapsules (NCs) loading benzophenone-3 (BZP3). NCs composed of poly(ε-caprolactone) carrot oil and Pluronic® F68 were produced by emulsification-diffusion method. Their mean particle size (Z-Ave) ranged from 280 to 420 nm, polydispersity index (PDI) was below 0.37, while zeta potential (ZP) reached about |+11 mV|. No cytotoxic effects were observed in L929 fibroblast cell line for the blank (i.e., non-loaded) NCs and BZP3-loaded NCs (BZP3-NCs). The semi-solid sunscreen formulation was stable over time (centrifugation testing) and exhibited non-Newtonian pseudoplastic behavior, which is typical of products for topical application onto the skin. The sun protection factor (SPF) value reached 8.84, when incorporating BZP3-NCs (SPF of 8.64) into the semi-solid formulation. A synergistic effect was also observed when combining the formulation ingredients of nanocapsules, i.e., SPF of carrot oil was 6.82, blank NCs was 6.84, and BZP3-loaded NCs was 8.64. From the hen's egg-chorioallantoic membrane test (HET-CAM) test, the non-irritation profile of the developed formulations could also be confirmed. The obtained results show a promising use of poly(ε-caprolactone) nanocapsules to be loaded with lipophilic sunscreens as benzophenone-3.

Innovative nanocompounds for cutaneous administration of classical antifungal drugs: a systematic review.

Nanomedicine manipulates materials at atomic, molecular, and supramolecular scale, with at least one dimension within the nanometer range, for biomedical applications. The resulting nanoparticles have been consistently shown beneficial effects for antifungal drugs delivery, overcoming the problems of low bioavailability and high toxicity of these drugs. Due to their unique features, namely the small mean particle size, nanoparticles contribute to the enhanced drug absorption and uptake by the target cells, potentiating the therapeutic drug effect. The topical route is desirable due to the adverse effects arising from oral administration. This review provides a comprehensive analysis of the use of nano compounds for the current treatment of topical fungal infections. A special emphasis is given to the employment of lipid nanoparticles, due to their recognized efficacy, versatility, and biocompatibility, attracting the major attention as novel topical nanocompounds used for the administration of antifungal drugs.

In vitro SPF and Photostability Assays of Emulsion Containing Nanoparticles with Vegetable Extracts Rich in Flavonoids.

The aim of study was to determine the in vitro sun protection factor (SPF) and the photostability profile of a topical formulation composed of nanoparticles loaded with vegetable extracts and to assess its physicochemical properties. Chitosan/tripolyphosphate (TPP) nanoparticles loaded with flavonoids-enriched vegetable extracts (Ginkgo biloba L., Dimorphandra mollis Benth, Ruta graveolens, and Vitis vinifera L.) were produced and characterized for their morphology, mean particle size, zeta potential, and encapsulation efficiency. A final topical formulation was obtained by dispersing chitosan/TPP nanoparticles in an o/w emulsion. Results showed that nanoparticles dispersion exhibited yellowish color, spherical shape, and uniform appearance. Extract-loaded chitosan/TPP nanoparticles showed a mean particle size of 557.11 ± 3.1 nm, polydispersity index of 0.39 ± 0.27, zeta potential of + 11.54 ± 2.1 mV, and encapsulation efficiency of 75.89% of rutin. The recorded texture parameters confirm that the developed formulation is appropriate for skin application. The SPF obtained was 2.3 ± 0.4, with a critical wavelength of 387.0 nm and 0.69 UVA/UVB ratio. The developed formulation exhibited photostability, allowing the release of flavonoids from nanoparticles while retaining rutin into the skin in a higher extension.

Influence of oil content on physicochemical properties and skin distribution of Nile red-loaded NLC.

The aims of this study were to investigate the effect of the oil content on the physicochemical properties of NLC and to elucidate the potential of NLC for skin targeting. The obtained results showed that an increase in the oil content did not affect the mean particle size of NLC but impacted on the zeta potential. The inner structure of NLC was influenced by the increasing proportion of oil towards the less ordered structure as confirmed by differential scanning calorimetry (DSC) and X-ray diffraction (XRD), particularly for the higher medium chain triglycerides (MCT) loading. The data from proton nuclear magnetic resonance (1H NMR) revealed that cetyl palmitate nanoparticles did not completely recrystallize after cooling down to room temperature. 1H NMR and DSC results indicate that MCT molecules were restricted in the NLC as compared to the nanoemulsions (NE). Nile red distribution and penetration into skin from NLC were pronounced as compared to NE and dependent on the MCT loading. The deep penetration and high amount of Nile red were related to the occlusion factor. Moreover, the epidermal targeting was achieved by NLC applications, particularly those containing 5% MCT (NLC-5) depending on the amount of MCT loading.