Preclinical studies of the antitumor effect of curcumin-loaded polymeric nanocapsules: A systematic review and meta-analysis.

Curcumin, a plant-derived compound, has various well-known biological effects (anti-inflammatory, antioxidant, antitumor, among others) as well as some important limitations for formulators, such as poor water solubility and low oral bioavailability. Its nanoencapsulation is reported to overcome these drawbacks and to improve its in vivo efficacy. Here, data from preclinical in vivo studies evaluating the antitumor efficacy of curcumin-loaded polymeric nanocapsules are collected, analyzed, and discussed as a systematic review. Meta-analyses are performed to assess the contribution of this nanoencapsulation compared with nonencapsulated curcumin. Eighteen studies (116 animals) meet the inclusion criteria. The evidence that curcumin-loaded polymeric nanocapsules inhibits tumor growth (SMD: -3.03; 95% CI: -3.84, -2.21; p < 0.00001) and decreases tumor weight (SMD: -3.96; 95% CI: -6.22, -1.70; p = 0.0006) in rodents is established, regardless of the solid tumor model. To assess the quality of the studies included in the review a bias risk analysis was performed using the SYRCLE's RoB tool. Therefore, encapsulation in polymeric nanocapsules represents an important tool to improve the antitumor effects of curcumin, and this systematic review paves the way for future clinical studies and the translation of curcumin formulations into novel nanomedicines for human cancer treatment.

The potential impact of vegetarian diet on the oral mucosa: A preliminary cytopathological study.

BACKGROUND/PURPOSE: Actually, many individuals have opted for the vegetarian diet. The objective of this study was to evaluate the impact of the vegetarian diet on the oral epithelium through cytopathology. METHODS: Oral smears of the tongue and buccal mucosa of 60 adult subjects (30 vegetarians and 30 controls) were collected. Smears were analyzed morphologically and for three morphometric variables: nucleus area (NA), cytoplasm area (CA) and nucleus/cytoplasm ratio. RESULTS: Vegetarians were classified as ovolactovegetarian (53.3%), vegans (30%) and strict vegetarians (16.7%). The NA and CA of the epithelial cells of vegetarian individuals were smaller when compared to controls both in the region of the buccal mucosa and tongue. However, there was no statistically significant difference according to the Student's t-test. For the NA/CA ratio, cells in the oral mucosa region were larger for vegetarians compared to controls. For the tongue, both groups had the same value and the Mann-Whitney U test confirmed that there is no difference between the groups for this cytomorphometric variable. RESULTS: Vegan individuals had a smaller (but not larger) area of CA when compared to controls for the tongue (vegan = 2604.2 ± 179.2 versus control = 3256.7 ± 463.8 p = 0.013). Most smears showed normal epithelial cells and some individuals had changes of an inflammatory nature, mainly in the tongue. CONCLUSION: Despite the small sample size, the results of this study raise the hypothesis that the vegetarian diet (especially the vegan diet) can compromise the thickness of the oral epithelium of the tongue.

Synthesis and biological evaluation of hydrazone derivatives as antifungal agents.

Emerging yeasts are among the most prevalent causes of systemic infections with high mortality rates and there is an urgent need to develop specific, effective and non-toxic antifungal agents to respond to this issue. In this study 35 aldehydes, hydrazones and hydrazines were obtained and their antifungal activity was evaluated against Candida species (C. parapsilosis, C. tropicalis, C. krusei, C. albicans, C. glabrata and C. lusitaneae) and Trichosporon asahii, in an in vitro screening. The minimum inhibitory concentrations (MICs) of the active compounds in the screening was determined against 10 clinical isolates of C. parapsilosis and 10 of T. asahii. The compounds 4-pyridin-2-ylbenzaldehyde] (13a) and tert-butyl-(2Z)-2-(3,4,5-trihydroxybenzylidine)hydrazine carboxylate (7b) showed the most promising MIC values in the range of 16-32 µg/mL and 8-16 µg/mL, respectively. The compounds' action on the stability of the cell membrane and cell wall was evaluated, which suggested the action of the compounds on the fungal cell membrane. Cell viability of leukocytes and an alkaline comet assay were performed to evaluate the cytotoxicity. Compound 13a was not cytotoxic at the active concentrations. These results support the discovery of promising candidates for the development of new antifungal agents.

Redispersible 3D printed nanomedicines: An original application of the semisolid extrusion technique.

Semisolid extrusion is a layer-by-layer 3D printing technique that produces objects from gels or pastes. This process can be carried out at room temperature, without using a light source, and has been explored in pharmaceutics in the last few years. In this regard, our group hypothesized its suitability for the production of three-dimensional (3D) printed nanomedicines containing drug-loaded organic nanocarriers. In this study, the original application of the semisolid extrusion was evaluated to produce redispersible 3D printed oral solid forms containing drug-loaded polymeric nanocapsules. A carboxymethyl cellulose hydrogel containing resveratrol and curcumin co-encapsulated in nanocapsules was prepared, and the nanocapsules did not change its complex viscosity and yield stress. Homogeneous and yellow cylindrical-shaped solid forms were printed, with a mean weight of 0.102 ± 0.015 g, a polyphenol content of approximately 160 µg/unit, disintegration time of <45 min, and recovery of the nanosized carriers. The polyphenols were completely released from the solid forms after 8 h, although part of them remained encapsulated in the nanocapsules. This study represents a proof of concept concerning the use of semisolid extrusion to produce 3D printed forms composed of polymeric nanocapsules in a one-step process. It proposes an original platform for the development of solid nanomedicines from liquid aqueous nanocapsule suspensions.

Drug-loaded mesoporous silica on carboxymethyl cellulose hydrogel: Development of innovative 3D printed hydrophilic films.

3D printing has been explored as an emerging technology for the development of versatile and printable materials for drug delivery. However, the alliance of 3D printing and nanomaterials has, to date, been little explored in pharmaceutics. Herein, a mesoporous silica with nanostructured pores, SBA-15, was used as a drug carrier for triamcinolone acetonide, a hydrophobic drug, with the aim of incorporating the drug formulation in a hydrophilic printable ink. The adsorption of the drug in the SBA-15 pores was confirmed by the decrease in its surface area and pore volume, along with an increase in the apparent aqueous solubility of triamcinolone acetonide, as shown by in vitro release studies. Thereafter, a hydrophilic ink composed of carboxymethyl cellulose containing drug-loaded SBA-15 was formulated and 3D printed as hydrophilic polymeric film using the semisolid extrusion technique (SSE). The 3D printed films showed complete drug release after 12 h, and the presence of the triamcinolone acetonide-loaded SBA-15 improved their in vitro mucoadhesion, suggesting their promising application in oral mucosa treatments. Besides representing an innovative platform to develop water-based mucoadhesive formulations containing a hydrophobic drug, this is the first report proposing the development of SSE 3D printed nanomedicines containing drug-loaded mesoporous silica.

Bioadhesive 3D-Printed Skin Drug Delivery Polymeric Films: From the Drug Loading in Mesoporous Silica to the Manufacturing Process.

The alliance between 3D printing and nanomaterials brings versatile properties to pharmaceuticals, but few studies have explored this approach in the development of skin delivery formulations. In this study, clobetasol propionate (CP) was loaded (about 25% w/w) in mesoporous silica nanomaterial (MSN) to formulate novel bioadhesive and hydrophilic skin delivery films composed of pectin (5% w/v) and carboxymethylcellulose (5% w/v) by 3D printing. As a hydrophobic model drug, CP was encapsulated in MSN at a 3:1 (w/w) ratio, resulting in a decrease of CP crystallinity and an increase of its dissolution efficiency after 72 h (65.70 ± 6.52%) as compared to CP dispersion (40.79 ± 4.75%), explained by its partial change to an amorphous form. The CP-loaded MSN was incorporated in an innovative hydrophilic 3D-printable ink composed of carboxymethylcellulose and pectin (1:1, w/w), which showed high tensile strength (3.613 ± 0.38 N, a homogenous drug dose (0.48 ± 0.032 mg/g per film) and complete CP release after 10 h. Moreover, the presence of pectin in the ink increased the skin adhesion of the films (work of adhesion of 782 ± 105 mN·mm). Therefore, the alliance between MSN and the novel printable ink composed of carboxymethylcellulose and pectin represents a new platform for the production of 3D-printed bioadhesive films, opening a new era in the development of skin delivery systems.

Salivary flow, amylase, and total protein in hospitalized patients with HIV infection / AIDS complications.

BACKGROUND: Saliva is a complex secretion produced daily by the salivary glands. Saliva consists mainly of water, enzymes, ions and amino acids and performs several important functions in oral health. OBJECTIVE: The aim of this study was to investigate the flow rate and concentrations of amylase and total proteins in the saliva of hospitalized patients due to AIDS complications. METHODS: Ninety-three men and women (20-64 years of age) were divided into two groups (46 HIV-infected patients and 47 controls) and had salivary flow rate and levels of amylase enzyme and total proteins evaluated. RESULT: The mean salivary flow rate was lower in individuals with HIV when compared to controls (P < 0.05). No significant difference between amylase enzyme levels and total proteins were observed in the saliva of patients with HIV infection when compared to controls. CONCLUSION: Individuals with HIV / AIDS infection (in hospital treatment) suffer no interference in levels of amylase and total salivary proteins, but they have significantly reduced salivary flow.