An innovative polysaccharide nanobased nail formulation for improvement of onychomycosis treatment.

Tioconazole-loaded nanocapsule suspensions and its coating with a cationic polymer were developed for nail drug delivery. The colloidal systems presented a nanometric size around 155nm for uncoated nanoparticles and 162nm for those with the cationic coating, with negative and positive zeta potential values, respectively. Both nanosuspensions showed drug content close to theoretical values (1mgmL-1), association efficiency close to 100% (HPLC) and were able to control tioconazol release. The developed formulations showed in vitro antifungal activity (agar diffusion method) against C. albicans. The cationic nanocapsules were considered bioadhesive, showed higher viscosity and were chosen to be incorporated into an ungueal formulation. Pullulan nanobased nail formulation showed adequate viscosity for nail application and drug content close to the theoretical values. It was equivalent to the commercial formulation Trosid® in preventing nail infection by T. rubrum in an in vitro onychomycosis model. The nanocapsule suspensions and Pullulan nanobased nail formulation showed lower irritant potential than the commercial formulation and than free drug in an in vitro evaluation. Pullulan nanobased nail formulation is promising for the treatment of onychomycosis.

Toxicity evaluation of the photoprotective compound LQFM048: Eye irritation, skin toxicity and genotoxic endpoints.

A new molecule, LQFM048, originally designed through molecular hybridization using green chemistry approach, is in development as a photoprotective agent. Eye irritation, skin toxicity and genotoxicity evaluations are mandatory for predicting health risks. In this context, the purpose of this study was to investigate the eye irritation potential of LQFM048 by combining Short Time Exposure (STE), Bovine Corneal Opacity and Permeability (BCOP) associated with corneal histomorphometry and Hen's Egg Test-Chorioallantoic Membrane (HET-CAM). Additionally, skin toxicity was evaluated by interleukin-18 production in the HaCaT keratinocyte, Local Lymph Node Assay (LLNA:BrdU-ELISA) method, 3T3 Neutral red uptake (NRU) assay and in vivo phototoxicity test. Genotoxic potential of LQFM048 was also analyzed by cytokinesis-block micronucleus assay (MNvit test-cytoB) in HepG2 cells. Our results showed that LQFM048 did not induce eye irritation and it was classified as UN GHS No Category for both STE and BCOP assays and non-irritating for HET-CAM test. LQFM048 showed non-potential skin sensitization with stimulation index (SI=0.7) in the LLNA:BrdU-ELISA method. Corroborating in vivo tests, it did not promote significant cytotoxicity in HaCaT cells and it showed similar levels of IL-18 when compared to control. Furthermore, LQFM048 induced non-phototoxic potential with photo-irritation factor (PIF) and mean photo effect (MPE) of 1 and -0.138, respectively, for 3T3 cells. Similarly, it was not phototoxic for in vivo testing with or without exposure to UVA, showing SI values of 1 and 1.2, respectively. The micronucleus test showed that LQFM048 was not genotoxic, under the conditions tested.In conclusion, LQFM048, a heterocyclic compound obtained through an environmentally acceptable simple synthetic route, seems to be safe for human use, especially for the development of a new sunscreen product, since it is neither an eye irritant, nor a contact allergen, nor mutagenic and nor phototoxic.

The use of nanoencapsulation to decrease human skin irritation caused by capsaicinoids.

Capsaicin, a topical analgesic used in the treatment of chronic pain, has irritant properties that frequently interrupt its use. In this work, the effect of nanoencapsulation of the main capsaicinoids (capsaicin and dihydrocapsaicin) on skin irritation was tested in humans. Skin tolerance of a novel vehicle composed of chitosan hydrogel containing nonloaded nanocapsules (CH-NC) was also evaluated. The chitosan hydrogel containing nanoencapsulated capsaicinoids (CH-NC-CP) did not cause skin irritation, as measured by an erythema probe and on a visual scale, while a formulation containing free capsaicinoids (chitosan gel with hydroalcoholic solution [CH-ET-CP]) and a commercially available capsaicinoids formulation caused skin irritation. Thirty-one percent of volunteers reported slight irritation one hour after application of CH-NC-CP, while moderate (46% [CH-ET-CP] and 23% [commercial product]) and severe (8% [CH-ET-CP] and 69% [commercial product]) irritation were described for the formulations containing free capsaicinoids. When CH-NC was applied to the skin, erythema was not observed and only 8% of volunteers felt slight irritation, which demonstrates the utility of the novel vehicle. A complementary in vitro skin permeation study showed that permeation of capsaicinoids through an epidermal human membrane was reduced but not prevented by nanoencapsulation.

Intrapleural low-dose silver nitrate elicits more pleural inflammation and less systemic inflammation than low-dose talc.

STUDY OBJECTIVES: Several systemic effects have been described after talc pleurodesis. The aim of this study was to assess the systemic response induced by low, nonpleurodesis-inducing doses of talc and silver nitrate in an experimental model in rabbits. DESIGN: Groups of six rabbits were injected intrapleurally with talc, 100 mg/kg or 400 mg/kg, and silver nitrate, 0.1% or 0.5%. After 6, 24, or 48 h, samples of blood and pleural fluid were collected and assayed for leukocytes, percentage of neutrophils, lactate dehydrogenase, interleukin-8, and vascular endothelial growth factor (VEGF) levels. Preinjection blood samples were used as normal blood controls. MEASUREMENTS AND RESULTS: Silver nitrate 0.1% induced a more intense pleural inflammation than that produced by talc 100 mg/kg. In contrast, talc 100 mg/kg induced a more pronounced acute systemic response with higher values of WBCs and neutrophils, whereas silver nitrate 0.1% produced no significant increases in leukocytes or neutrophils. The serum interleukin-8 and VEGF levels increased in all groups, and decreased with time only in the silver nitrate 0.1% group. The highest serum VEGF levels were observed in the talc 100 mg/kg group. CONCLUSIONS: In conclusion, 0.1% silver nitrate produced an intense pleural inflammatory response with a less evident systemic response in comparison to 0.5% silver nitrate and talc 100 mg/kg or 400 mg/kg.

Management of malignancy-associated pleural effusion: current and future treatment strategies.

Management of recurrent malignant pleural effusion, a common complication of malignancy, poses a challenge to clinicians. Although almost one century has elapsed since the introduction of the pleurodesis procedure, the ideal approach and best agent are still to be defined. Optimally, pleurodesis should be done at the bedside with a minimally invasive procedure, and suitable agents to achieve pleural symphysis should be inexpensive, available worldwide and free of adverse effects. To date, no substance completely fulfills these requirements. Silver nitrate should be considered for pleurodesis because of its low cost and ease of handling. Although talc has been used most frequently to induce pleurodesis, reports of death due to acute respiratory failure have raised concerns about the safety of this agent. Tetracycline, an effective alternative used in the past, is no longer commercially available. This agent has been substituted with derivatives of tetracycline, such as minocycline and doxycycline with success rates similar to those with tetracycline. Several antineoplastic agents have been injected into the pleural space with the aim of producing pleural symphysis, the most representative of this group being bleomycin. Recent knowledge of the molecular mechanisms involved in pleural inflammation has brought into focus new substances, such as transforming growth factor beta and vascular endothelial growth factor, which may be used as pleurodesis agents in the future. Nevertheless, more studies are necessary to better define the potential of these substances in the induction of pleural symphysis.Ideally, a sclerosing agent should be cost-effective, available worldwide and easily administered. Talc will probably stand as the preferred agent to be used for pleurodesis in malignant pleural effusion because of its efficacy, easy manipulation and handling. However, further investigation is necessary to minimize adverse effects related to talc.

Topical immune modulation with dinitrochlorobenzene in HIV disease: a controlled trial from Brazil.

OBJECTIVE: Despite the rapid spread of human immunodeficiency virus (HIV) in the developing countries of Africa, Asia and Latin America, accessible and affordable antiretroviral therapies have not been developed. Dinitrochlorobenzene (DNCB) is an inexpensive contact sensitizing agent that stimulates cell-mediated immunity when applied to the skin. We have examined the clinical and immunologic effects of topical DNCB therapy in a cohort of indigent patients with HIV disease from Brazil. DESIGN AND METHODS: Thirty-five HIV-infected subjects were divided into a control group that refused DNCB therapy (6 patients) and a treatment group that applied topical DNCB on a weekly basis throughout the study (29 patients). Subjects were monitored for adverse clinical events, progression to AIDS and changes in body weight. CD4 and CD8 T-cell counts were also monitored in both groups. RESULTS: Control and treated patients were evenly matched in terms of age, initial clinical status and prior adverse clinical events. The mean follow-up was 19.7 months for the control group and 17.8 months for the DNCB group. Control patients had significantly more adverse clinical events and progression to AIDS during the study than the treatment group (p = 0.002 and p = 0.013, respectively). There were no deaths in either group. Control patient weights decreased over the study period while DNCB patient weights increased (p < 0.001). CD4 and CD8 T-cell counts decreased significantly in the control group and increased in the DNCB group (p < 0.001 and p = 0.031, respectively). DNCB therapy was well tolerated. CONCLUSIONS: Topical DNCB therapy affords a rational, effective and inexpensive treatment approach for HIV disease. DNCB should benefit patients in developing nations with limited access to health care.