Karaya/Gellan-Gum-Based Bilayer Films Containing 3,3'-Diindolylmethane-Loaded Nanocapsules: A Promising Alternative to Melanoma Topical Treatment.

This study aimed to incorporate nanocapsules containing 3,3'-diindolylmethane (DIM) with antitumor activity into a bilayer film of karaya and gellan gums for use in topical melanoma therapy. Nanocarriers and films were prepared by interfacial deposition of the preformed polymer and solvent casting methods, respectively. Incorporating DIM into nanocapsules increased its antitumor potential against human melanoma cells (A-375) (IC50 > 24.00 µg/mL free DIM × 2.89 µg/mL nanocapsules). The films were transparent, hydrophilic (θ < 90°), had homogeneous thickness and weight, and had a DIM content of 106 µg/cm2. Radical ABTS+ scavenger assay showed that the DIM films presented promising antioxidant action. Remarkably, the films showed selective bioadhesive potential on the karaya gum side. Considering the mechanical analyses, the nanotechnology-based films presented appropriate behavior for cutaneous application and controlled DIM release profile, which could increase the residence time on the application site. Furthermore, the nanofilms were found to increase the permeation of DIM into the epidermis, where melanoma develops. Lastly, the films were non-hemolytic (hemolysis test) and non-irritant (HET-CAM assay). In summary, the combination of karaya and gellan gum in bilayer films that contain nanoencapsulated DIM has demonstrated potential in the topical treatment of melanoma and could serve as a viable option for administering DIM for cutaneous melanoma therapy.

Cationic nanocapsule suspension as an alternative to the sublingual delivery of nifedipine.

Nifedipine (NIFE) is a calcium channel blocker drug used to treat cardiovascular diseases, angina, and hypertension. However, NIFE is photolabile, has a short biological half-life, low aqueous solubility, and undergoes an intense first-pass effect, compromising its oral bioavailability. Thus, this study aimed to develop NIFE-loaded nanocapsules for sublingual administration. Nanocapsule suspensions of Eudragit® RS100 and medium chain triglycerides containing NIFE were prepared by the interfacial deposition of preformed polymer technique. The developed formulations showed particle size around 170 nm, polydispersity index below 0.2, positive zeta potential, and acid pH. The NIFE content was 0.98 ± 0.03 mg/mL, and the encapsulation efficiency was 99.9%. The natural light photodegradation experiment showed that the nanocapsules were able to provide NIFE photoprotection. The nanocapsules reduced the cytotoxicity of NIFE and showed no genotoxic effects in the Allium cepa model. Through the HET-CAM test, the formulations were classified as non-irritating. The developed nanocapsule suspension demonstrated a controlled release of NIFE and mucoadhesive potential. The in vitro permeation assay showed that the nanocapsules favored the NIFE permeation to the receptor compartment. In addition, the nanocapsules provided greater drug retention in the mucosa. Thus, the development of polymeric nanocapsule suspensions showed that this system could be a promising platform for NIFE sublingual administration.

Locust bean gum hydrogels are bioadhesive and improve indole-3-carbinol cutaneous permeation: influence of the polysaccharide concentration

Abstract The locust bean gum (LBG) is a polysaccharide with thickening, stabilizing and gelling properties and it has been used in the preparation of pharmaceutical formulations. Hydrogels (HGs) are obtained from natural or synthetic materials that present interesting properties for skin application. This study aimed to develop HGs from LBG using indole-3-carbinol (I3C) as an asset model for cutaneous application. HGs were prepared by dispersing LBG (2%, 3% and 4% w/v) directly in cold water. The formulations showed content close to 0.5 mg/g (HPLC) and pH ranging from 7.25 to 7.41 (potentiometry). The spreadability factor (parallel plate method) was inversely proportional to LBG concentration. The rheological evaluation (rotational viscometer) demonstrated a non-Newtonian pseudoplastic flow behavior (Ostwald De Weale model), which is interesting for cutaneous application. The HET-CAM evaluation showed the non-irritating characteristic of the formulations. The bioadhesive potential demonstrated bioadhesion in a concentration-dependent manner. Permeation in human skin using Franz cells showed that the highest LBG concentration improved the skin distribution profile with greater I3C amounts in the viable skin layers. The present study demonstrated the feasibility of preparing HGs with LBG and the formulation with the highest polymer concentration was the most promising to transport active ingredients through the skin.

Chrysin loaded lipid-core nanocapsules ameliorates neurobehavioral alterations induced by ß-amyloid1-42 in aged female mice.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a clinically and progressive loss of cognitive function, neuropsychiatric and behavioral disorders. Some studies showed that chrysin has antioxidant and anti-inflammatory properties. However, your bioavailability is relatively low. Therefore, the present study was designed to investigate the effects of chrysin loaded lipid-core nanocapsules (LNCs) on neurochemical and behavioral changes in a model of AD induced by ß-amyloid1-42 (Aß1-42) peptide in aged female mice. For this purpose, aged female mice received free chrysin (FC) (5 mg/kg, per oral, p.o.) or chrysin loaded LNCs (C1-LNC and C5-LNC) (1 or 5 mg/kg, p.o.) for 14 days after Aß1-42 administration (400 pmol, i.c.v.). Aß1-42 induced significant impairments on memory and learning (morris water maze task, object recognition and step-down-type passive avoidance), also caused oxidative stress, reduced the levels of brain-derived neurotrophic factor (BDNF), increased neuroinflammation in prefrontal cortex and hippocampus of aged animals. Thus, C1-LNC and C5-LNC displayed significant effect against Aß1-42, via attenuation of oxidative stress and neuroinflammation, modulation of neurochemical and behavioral changes in a model of AD. These results point to chrysin loaded LNCs (mainly C5-LNC) can be a promising biomedical tool and a new therapeutic approach for treatment and prevention of AD.

Gellan gum-based hydrogel containing nanocapsules for vaginal indole-3-carbinol delivery in trichomoniasis treatment.

Trichomonas vaginalis infection is the STI most common worldwide. Indole-3-carbinol (I3C) is a phytochemical presenting promising biological activities. In this study, design, formulation, and evaluation of a vaginal hydrogel containing I3C-loaded nanocapsules for the treatment of trichomoniasis have been investigated. Nanocapsules of Eudragit® RS100 and rosehip oil containing I3C (NC-I3C) were prepared by interfacial deposition of preformed polymer method. In vitro evaluations showed that free I3C (IC50 = 3.36 µg/mL) was able to reduce the trophozoites viability at higher concentrations (3.13 and 6.25 µg/mL), while nanoencapsulation (IC50 = 2.09 µg/mL) reduced the viability at all concentrations evaluated. Comparing free and nanoencapsulated I3C, we observe that nanoencapsulation improved anti-T. vaginalis activity. In order to obtain a formulation for vaginal administration, hydrogels (HG-NC-I3C) were prepared by thickening the NC-I3C with gellan gum. HG-NC-I3C presented particle size below 195 nm, low polydispersity index (<0.2), I3C content = 0.50 ± 0.01 mg/g, pH = 7.05, non-Newtonian pseudoplastic flow behavior and exhibited mucoadhesion to cow's vaginal mucosa. Evaluation of irritation potential by chorioallantoic membrane method indicated that the formulations are considered non-irritating. Besides that, permeation through the cow's vaginal mucosa showed that nanoencapsulation promoted I3C controlled release. This way, the developed HG-NC-I3C can be considered a promising approach for trichomoniasis treatment through vaginal administration.

Co-encapsulation of acyclovir and curcumin into microparticles improves the physicochemical characteristics and potentiates in vitro antiviral action: Influence of the polymeric composition.

The present study developed and characterized microparticles formulations containing acyclovir and curcumin co-encapsulated in order to overcome the biopharmaceutical limitations and increase the antiviral effect of both drugs. The microparticles were prepared by a spray drying methodology following the ratio 1:3 (drug:polymer), which were made by hydroxypropylmethylcellulose (HPMC) and/or Eudragit® RS100 (EUD). The MP-1 formulation was composed of HPMC and EUD (1:1), MP-2 formulation was composed only of HPMC and MP-3 formulation was composed only of EUD. All formulations showed yielding around 50% and acceptable powder flowability. Drug content determination around 82.1-96.8% and 81.8-87% for acyclovir and curcumin, respectively. The microparticles had spherical shape, size within 11.5-15.3 µm, unimodal distribution and no chemical interactions among the components of the formulations. Of particular importance, the polymeric composition considerably influenced on the release profile of the drugs. The in vitro release experiment demonstrated that the microencapsulation provided a sustained release of acyclovir as well as increased the solubility of curcumin. Besides, mathematical modeling indicated that the experimental fit biexponential equation. Importantly, drugs microencapsulation promoted superior antiviral effect against BoVH-1 virus in comparison to their free form, which could be attributed to the improvement in the aforementioned physicochemical parameters. Therefore, these formulations could be promising technological drug carriers for acyclovir and curcumin, which highlight the great offering a potential alternative treatment for viral herpes.