Lucas Almeida Rigo

Nanoencapsulation of rice bran oil increases its protective effects against UVB radiation-induced skin injury in mice.

Excessive UV-B radiation by sunlight produces inflammatory and oxidative damage of skin, which can lead to sunburn, photoaging, and cancer. This study evaluated whether nanoencapsulation improves the protective effects of rice bran oil against UVB radiation-induced skin damage in mice. Lipid-core nanocapsules containing rice bran oil were prepared, and had mean size around 200 nm, negative zeta potential (∼-9 mV), and low polydispersity index (<0.20). In order to allow application on the skin, a hydrogel containing the nanoencapsulated rice bran oil was prepared. This formulation was able to prevent ear edema induced by UVB irradiation by 60 ± 9%, when compared with a hydrogel containing LNC prepared with a mixture of medium chain triglycerides instead of rice bran oil. Protein carbonylation levels (biomarker of oxidative stress) and NF-κB nuclear translocation (biomarker of pro-inflammatory and carcinogenesis response) were reduced (81% and 87%, respectively) in animals treated with the hydrogel containing the nanoencapsulated rice bran oil. These in vivo results demonstrate the beneficial effects of nanoencapsulation to improve the protective properties of rice bran oil on skin damage caused by UVB exposure.

Nanocarriers for optimizing the balance between interfollicular permeation and follicular uptake of topically applied clobetasol to minimize adverse effects.

The treatment of various hair disorders has become a central focus of good dermatologic patient care as it affects men and women all over the world. For many inflammatory-based scalp diseases, glucocorticoids are an essential part of treatment, even though they are known to cause systemic as well as local adverse effects when applied topically. Therefore, efficient targeting and avoidance of these side effects are of utmost importance. Optimizing the balance between drug release, interfollicular permeation, and follicular uptake may allow minimizing these adverse events and simultaneously improve drug delivery, given that one succeeds in targeting a sustained release formulation to the hair follicle. To test this hypothesis, three types of polymeric nanocarriers (nanospheres, nanocapsules, lipid-core nanocapsules) for the potent glucocorticoid clobetasol propionate (CP) were prepared. They all exhibited a sustained release of drug, as was desired. The particles were formulated as a dispersion and hydrogel and (partially) labeled with Rhodamin B for quantification purposes. Follicular uptake was investigated using the Differential Stripping method and was found highest for nanocapsules in dispersion after application of massage. Moreover, the active ingredient (CP) as well as the nanocarrier (Rhodamin B labeled polymer) recovered in the hair follicle were measured simultaneously, revealing an equivalent uptake of both. In contrast, only negligible amounts of CP could be detected in the hair follicle when applied as free drug in solution or hydrogel, regardless of any massage. Skin permeation experiments using heat-separated human epidermis mounted in Franz Diffusion cells revealed equivalent reduced transdermal permeability for all nanocarriers in comparison to application of the free drug. Combining these results, nanocapsules formulated as an aqueous dispersion and applied by massage appeare to be a good candidate to maximize follicular targeting and minimize drug penetration into the interfollicular epidermis. We conclude that such nanotechnology-based formulations provide a viable strategy for more efficient drug delivery to the hair follicle. Moreover, they present a way to minimize adverse effects of potent glucocorticoids by releasing the drug in a controlled manner and simultaneously decreasing interfollicular permeation, offering an advantage over conventional formulations for inflammatory-based skin/scalp diseases.

Influence of the type of vegetable oil on the drug release profile from lipid-core nanocapsules and in vivo genotoxicity study.

Abstract The use of rice bran (RB), soybean (SB) or sunflower seed (SF) oils to prepare lipid-core nanocapsules (LNCs) as controlled drug delivery systems was investigated. LNCs were prepared by interfacial deposition using the preformed polymer method. All formulations showed negative zeta potential and adequate nanotechnological characteristics (particle size 220–230 nm, polydispersity index < 0.20). The environmental safety was evaluated through an in vivo protocol (Allium cepa test) and LNCs containing RB, SB or SF oils did not present genotoxic potential. Clobetasol propionate (CP) was selected as a model drug to evaluate the influence of the type of vegetable oil on the control of the drug release from LNCs. Biphasic drug release profiles were observed for all formulations. After 168 h, the concentration of drug released from the formulation containing SF oil was lower (0.36 mg/mL) than from formulations containing SB (0.40 mg/mL) or RB oil (0.45 mg/mL). Good correlations between the consistency indices for the LNC cores and the burst and sustained drug release rate constants were obtained. Therefore, the type of the vegetal oil was shown as an important factor governing the control of drug release from LNCs.

Improved tretinoin photostability in a topical nanomedicine replacing original liquid suspension with spray-dried powder with no loss of effectiveness

Objective: The use of spray-dried powders containing tretinoin-loaded nanocapsules instead of the original liquid suspension, aimed at the preparation of dermatological nanomedicines with improved photostability, was investigated. Methods: Powders were prepared using lactose as a drying adjuvant. Hydrogels were prepared using two approaches: dispersing Carbopol Ultrez 10® in an aqueous redispersion of the powder or incorporating the powder in previously formed hydrogels. Results and discussion: The photodegradation of tretinoin in hydrogels prepared with the powders showed similar half-life times (around 19.5 h) compared to preparations with the original liquid nanocapsules (20.7 ± 1.4 h), regardless of the preparation approach. In addition, the topical nanomedicines prepared with the spray-dried powders presented a significant improvement in tretinoin photostability compared to the formulation containing the non-encapsulated drug. Conclusion: This study verified that the addition of the spray-dried powders containing tretinoin-loaded lipid-core nanocapsules to hydrogels did not influence the photoprotection of the drug compared with the preparation procedure using the original liquid suspension.

Redispersible spray-dried nanocapsules for the development of skin delivery systems: proposing a novel blend of drying adjuvants

ABSTRACT This study proposes a novel blend of drying adjuvants (lactose and polyvinylpyrrolidone) as an approach to produce dispersible powders containing nanocapsules for the development of skin delivery systems. Hydrogels were produced with liquid nanocapsules and spray-dried powders. Nanoparticle recovery was obtained after powder aqueous redispersion. No influence of the intermediate product was observed on the hydrogel properties and on the drug release profile. The novel blend of drying adjuvants is a smart approach to obtain dried nanocapsules with excellent aqueous redispersion and to maintain the drug release profile of the original suspension in the design of novel skin delivery systems.

Nanoencapsulation of a glucocorticoid improves barrier function and anti-inflammatory effect on monolayers of pulmonary epithelial cell lines

Graphical abstract Figure. No Caption available. Abstract The anti‐inflammatory effect of polymeric deflazacort nanocapsules (NC‐DFZ) was investigated, and possible improvement of epithelial barrier function using filter grown monolayers of Calu‐3 cells was assessed. NC prepared from poly(&egr;‐caprolactone) (PCL) had a mean size around 200 nm, slightly negative zeta potential (˜−8 mV), and low polydispersity index (<0.10). Encapsulation of DFZ had an efficiency of 85%. No cytotoxic effects were observed at particle concentration of 9.85 × 1011 NC/ml, which was therefore chosen to evaluate the effect of NC‐DFZ at 1% (w/v) of PCL and 0.5% (w/v) of DFZ on the epithelial barrier function of Calu‐3 monolayers. Nanoencapsulated drug at 0.5% (w/v) increased transepithelial electrical resistance and decreased permeability of the paracellular marker sodium fluorescein, while non‐encapsulated DFZ failed to improve these parameters. Moreover, NC‐DFZ reduced the lipopolysaccharide (LPS) mediated secretion of the inflammatory marker IL‐8. In vitro dissolution testing revealed controlled release of DFZ from nanocapsules, which may explain the improved effect of DFZ on the cells. These data suggest that nanoencapsulation of pulmonary delivered corticosteroids could be advantageous for the treatment of inflammatory conditions, such as asthma and chronic obstructive pulmonary diseases.

Intracellular Delivery of Poorly Soluble Polyphenols: Elucidating the Interplay of Self-Assembling Nanocarriers and Human Chondrocytes

Increased molecular understanding of multifactorial diseases paves the way for novel therapeutic approaches requiring sophisticated carriers for intracellular delivery of actives. We designed and characterized self-assembling lipid-core nanocapsules for coencapsulation of two poorly soluble natural polyphenols curcumin and resveratrol. The polyphenols were identified as high-potential therapeutic candidates intervening in the intracellular inflammation cascade of chondrocytes during the progress of osteoarthritis. To elucidate the interplay between chondrocytes and nanocapsules and their therapeutic effect, we pursued a complementary analytical approach combining label-free visualization with biological assays. Primary human chondrocytes did not show any adverse effects upon nanocapsule application and coherent anti-Stokes Raman scattering images visualized their intracellular uptake. Further, by systematically blocking different uptake mechanisms, an energy independent uptake into the cells could be identified. Additionally, we tested the therapeutic effect of the polyphenol-loaded carriers on inflamed chondrocytes. Treatment with nanocapsules resulted in a major reduction of nitric oxide levels, a well-known apoptosis trigger during the course of osteoarthritis. For a more profound examination of this protective effect on joint cells, we pursued studies with atomic force microscopy investigations. Significant changes in the cell cytoskeleton as well as prominent dents in the cell membrane upon induced apoptosis were revealed. Interestingly, these effects could not be detected for chondrocytes which were pretreated with the nanocapsules. Overall, besides presenting a sophisticated carrier system for joint application, these results highlight the necessity of establishing combinatorial analytical approaches to elucidate cellular uptake, the interplay of codelivered drugs and their therapeutic effect on the subcellular level.

Diminazene Aceturate Liposomes: Morphometric and Biochemical Liver, Kidney, and Spleen of Rats Infected with Trypanosoma evansi

The aim of this study was to evaluate the effect of treatment with liposomal (L-DMZ) and conventional (C-DMZ) diminazene aceturate formulations on hepatic and renal functions of rats, experimentally infected with Trypanosoma evansi. For this purpose, 72 Wistar rats (Rattus norvegicus) were divided into six groups (A, B, C, D, E, and F). Each group was subdivided into two other subgroups in order to assess the biochemical and histological results on days 7 and 40 post-treatment (PT). Treatments were carried out based on two different therapeutic protocols: L-DMZ and C-DMZ at 3.5mg/kg(-1), single dose (groups C and D), and five successive doses within intervals of 24h (groups E and F). Groups A and B corresponded to uninfected and infected (without treatment) animals, respectively. Sample collections were held on days 7 and 40 PT for the assessment of hepatic [alkaline phosphatase (AP), alanine transferase (ALT), albumin, gamma glutamil transferase (GGT) and renal functions (creatinine and urea). Additionally, the histology of fragments of liver, kidney, and spleen was performed. Animals in group B showed a significant increase in AP, GGT, ALT, and urea when compared with group A. On day 7 post-inoculation (PI), the biochemical analysis showed a reduction (P<0.05) of AP and GGT, while the levels of urea were increased in groups C, D, E, F. On day 40 PT, ALT was increased in these same groups when compared with group A. In histopathology, changes in liver samples were observed on day 7 PT in groups D and F, especially regarding the area and density of the hepatocytes. Renal analysis exhibited changes in glomerular space, glomerular, and corpuscular areas in group E. Therefore, these results allowed us to conclude that the treatment with L-DMZ and C-DMZ led to variable biochemical changes, which defined the functions of the liver and kidneys of treated animals, since the main histopathology alterations were observed in animals treated with liposomes, at their higher dosages. Thus, treatments with L-DMZ and C-DMZ in five consecutive doses were effective although being followed by liver toxicity.

Rice Bran Oil: Benefits to Health and Applications in Pharmaceutical Formulations

Abstract Rice bran oil (RBO) is obtained from bran, a by-product of the rice bran milling process. Scientific interest in RBO oil is recent compared to major edible vegetable oils. It presents several phytochemical compounds with beneficial therapeutic effects, such as antioxidant, anti-inflammatory, and hypoglycemic. γ-Oryzanol is a potent antioxidant component present only in rice bran oil. In recent years, research has focused on the development of new pharmaceutical dosage forms, cosmetic formulations, or food products containing biological compounds obtained from rice bran oil to improve the treatment of diseases and human health. In this scenario, this chapter covers relevant aspects of RBO, including source and composition, beneficial effects on treating several diseases, and applications in the development of pharmaceutical or cosmetic formulations.Rice bran oil (RBO) is obtained from bran, a by-product of the rice bran milling process. Scientific interest in RBO oil is recent compared to major edible vegetable oils. It presents several phytochemical compounds with beneficial therapeutic effects, such as antioxidant, anti-inflammatory, and hypoglycemic. γ-Oryzanol is a potent antioxidant component present only in rice bran oil. In recent years, research has focused on the development of new pharmaceutical dosage forms, cosmetic formulations, or food products containing biological compounds obtained from rice bran oil to improve the treatment of diseases and human health. In this scenario, this chapter covers relevant aspects of RBO, including source and composition, beneficial effects on treating several diseases, and applications in the development of pharmaceutical or cosmetic formulations.