Thermosensitive and mucoadhesive hydrogel containing curcumin-loaded lipid-core nanocapsules coated with chitosan for the treatment of oral squamous cell carcinoma.

Buccal drug administration may be chosen as a medication route to treat various diseases for local or systemic effects. This study proposes the development of a thermosensitive hydrogel containing curcumin-loaded lipid-core nanocapsules coated with chitosan to increase mucoadhesion, circumventing several limitations of this route of administration. Hydroxypropylmethylcellulose and Poloxamer® 407 were incorporated for hydrogel production. Physicochemical characterization parameters, such as particle size distribution, mean diameter, polydispersity index, zeta potential, and morphology, were analyzed. Spherical homogeneous particles were obtained with average diameter, of 173 ± 22 nm for LNCc (curcumin lipid-core nanocapsules) and 179 ± 48 nm for CLNCc (chitosan-curcumin lipid-core nanocapsules). A PDI equal to 0.09 ± 0.02 for LNCc and 0.26 ± 0.01 for CLNCc confirmed homogeneity. Tensile analysis and washability test on porcine buccal mucosa indicated higher mucoadhesion for hydrogels in comparison to the nanocapsules in suspension, remaining on the mucous membrane up to 8 h (10.92 ± 3.95 µg of curcumin washed for H-LNCc and 28.41 ± 24.47 µg for H-CLNCc) versus the latter, which remained washed on the membrane for 90 min only (62.60 ± 4.72 µg for LNCc and 52.08 ± 1.63 µg for CLNCc). The irritant potential (IR) of the formulations was evaluated by the hen's egg chorioallantoic membrane test (HET-CAM), with no irritation phenomena observed. Formulations were tested for their efficacy in an in vitro model against oral squamous cancer cell line, showing a significant reduction in cell viability on all tested groups. These findings demonstrated that the proposed nanosystem is mucoadhesive and has potential to deliver buccal treatments.

Ionic liquid-loaded microcapsules doped into dental resin infiltrants.

Resin infiltrants have been effectively applied in dentistry to manage non-cavitated carious lesions in proximal dental surfaces. However, the common formulations are composed of inert methacrylate monomers. In this study, we developed a novel resin infiltrant with microcapsules loaded with an ionic liquid (MC-IL), and analyzed the physical properties and cytotoxicity of the dental resin. First, the ionic liquid 1-n-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide (BMI.NTf2) was synthesized. BMI.NTf2 has previously shown antibacterial activity in a dental resin. Then, MC-IL were synthesized by the deposition of a preformed polymer. The MC-IL were analyzed for particle size and de-agglomeration effect via laser diffraction analysis and shape via scanning electron microscopy (SEM). The infiltrants were formulated, and the MC-IL were incorporated at 2.5%, 5%, and 10 wt%. A group without MC-IL was used as a control. The infiltrants were evaluated for ultimate tensile strength (UTS), contact angle, surface free energy (SFE), and cytotoxicity. The MC-IL showed a mean particle size of 1.64 (±0.08) µm, shriveled aspect, and a de-agglomeration profile suggestive of nanoparticles' presence in the synthesized powder. There were no differences in UTS among groups (p > 0.05). The incorporation of 10 wt% of MC-IL increased the contact angle (p < 0.05), while the addition from 5 wt% reduced the SFE in comparison to the control group (p < 0.05). The human cell viability was above 90% for all groups (p > 0.05). The incorporation of microcapsules as a drug-delivery system for ionic liquids may be a promising strategy to improve dental restorative materials.

Phenytoin-loaded lipid-core nanocapsules improve the technological properties and in vivo performance of fluidised bed granules.

Lipid-core nanocapsules (LNCs) were recently reported by our group as a suitable binder system to produce fluidised bed granules. However, there is still a lack of knowledge about the influence of using these nanocarriers loaded with a drug on the properties of the granules and their in vivo performance. Therefore, this study was designed to produce innovative fluidised bed granules containing phenytoin-loaded LNCs (LNCPHT) as a strategy to evaluate the influence of the presence of the drug-loaded nanocarriers on their in vitro and in vivo properties. Granules were produced using a mixture of maltodextrin and phenytoin (1:0.004 w/w) as substrate. They were prepared by fluid bed granulation using water or LNCPHT as the liquid binder, affording good yields (73-82%) of granules with low moisture content (<5%). Granules prepared with LNCPHT had larger mean size (122 µm) compared to maltodextrin primary particles (50 µm) due to the formation of solid bridges. Moreover, the use of LNCPHT as the liquid binder improved their powder flow properties. The nanocarriers were recovered after aqueous dispersion (3.00 mg.mL-1 of PHT) with a redispersibility close to 90%. After reconstitution in water, granules containing LNCPHT showed an improved dissolution behaviour compared to those prepared without them. In addition, they showed a higher mucoadhesive effect due to a combined effect of the LNCPHT and maltodextrin in the interactions with porcine intestinal mucosa. Regarding the in vivo studies, granules containing the combination of non-encapsulated PHT and PHT-loaded lipid-core nanocapsules increased the latency to seizures compared to placebo granules, showing effective anticonvulsant effect in mice. In conclusion, the use of drug-loaded nanocapsules as binder is an encouraging approach to produce fluidised bed mucoadhesive granules with improved technological properties and in vivo performance.

Azelaic acid-loaded nanoemulsion with hyaluronic acid - a new strategy to treat hyperpigmentary skin disorders.

OBJECTIVE: To develop an azelaic acid (AzA)-loaded nanoemulsion with hyaluronic acid (HA) as a double targeting strategy to increase drug retention and tyrosinase inhibition activity. SIGNIFICANCE: Dermic melasma is a recalcitrant disease. Therefore, the development of new technologies that allow a deeper penetration in the skin while enhancing the efficacy of a safe and well-known dermatological active, like AzA, is a very promising alternative to improve the treatment of this disease. METHODS: An oil-in-water nanoemulsion was developed and characterized according to its droplet size distribution, zeta potential, pH value, drug content, encapsulation efficiency, spectroscopic characteristics, morphology, and stability. In vitro mushroom tyrosinase inhibition assay, cytotoxicity, and permeation studies were performed. A descriptive sensory evaluation was also carried out. RESULTS: Drug content was 10 mg/ml, particle size 419 ± 23 nm with monomodal distribution, encapsulation efficiency was 84.65%, zeta potential -10.9 ± 0.44 mV and pH 5.01 ± 0.01. The nanoemulsion was stable for 30 days (30 °C/65% RH). The nanoemulsion decreased tyrosinase activity and permeated through the skin, reaching viable epidermis and dermis and did not show signs of cytotoxicity. Sensory evaluation profile showed a higher spreadability with lesser whitening residue. CONCLUSION: The nanoemulsion presented characteristics within the nanoscale and reached the deeper layers of the skin while improving in vitro tyrosinase inhibition; hence, it could be a promising treatment to dermic melasma.

Antimicrobial and anti-inflammatory drug-delivery systems at endodontic reparative material: Synthesis and characterization.

OBJECTIVE: The aim of this study was to synthesize and characterize an experimental endodontic paste. METHODS: An experimental endodontic paste (EX) was characterized by its particle size, zeta potential, drug content and morphology. The powder of EX is composed of amoxicillin microspheres, calcium tungstate and α-tricalcium phosphate, mixed with an indomethacin nanocapsules suspension. Ultracal® (Ultradent), an iodoform-based paste (GP) and the EX were evaluated by its physical properties (flow, film thickness and radiopacity). The cytocompatibility was performed by MTT and SRB-colorimetric assays; the cell-migration was tested with scratch assay and cell-ability to remineralization with ALP and Alizarin Red S, with fibroblastic cell line. The antibacterial activity was assessed by the formation of inhibition zones and against planktonic bacteria. RESULTS: The EX and UL flow achieved ISO6876 standard, and GP was lower than 17mm. All pastes achieved the film thickness required. Radiopacity was equivalent to 1.81±0.25mmAl for EX, which did not differ from GP group 1.39±0.33mmAl (p>0.05). The UL presented 3.04±0.33mmAl. The values for SRB showed better citocompatibility in comparison with MTT for all materials. The ALP activity and formation of mineralized nodules demonstrated the remineralization potential for UL and EX. Cell migration showed continuous wound closure until complete cell healing, however, the EX accelerated the process (p<0.05). The EX showed the greatest inhibition zone (p<0.05) and was the only group with antibacterial activity against planktonic bacteria. SIGNIFICANCE: The synthesized endodontic paste demonstrated reliable physical and biological properties and could be a promising material for periapical tissue repair.

Buccal Bullfrog (Rana catesbeiana Shaw) Oil Emulsion: A Mucoadhesive System Intended for Treatment of Oral Candidiasis.

Oral candidiasis (OC) is an infectious disease caused by microorganisms of the genus Candida, leading to lesions in the buccal cavity. Its treatment consists of the administration of topical or systemic antifungal agents, which may compromise the patient compliance due to its side effects, highlighting the need for alternative treatments. In this scenario, bullfrog oil, an animal oil composed of a pool of saturated and unsaturated fatty acids, is introduced as a potential antifungal raw material. Thus, the aim of this work was to produce a mucoadhesive emulsified system able to deliver the bullfrog oil in the buccal cavity to treat the OC. The emulsion was produced and characterized by visual inspection, droplet size, polydispersity index (PdI), and zeta potential over the course of 60 days. In addition, its mucoadhesive ability was evaluated using an in vitro mucin model. The antifungal activity, evaluated by the broth microdilution assay and the biocompatibility, performed against human erythrocytes, were also carried out. The emulsion showed a droplet size of 320.79 ± 35.60 nm, a PdI of 0.49 ± 0.08, and a zeta potential of -38.53 ± 6.23 mV, with no significant changes over 60 days. The mucoadhesive properties of the system was improved by the use of pharmaceutical excipients. The antifungal activity showed that the bullfrog oil and the emulsion were able to inhibit the growth of different Candida species. Furthermore, the emulsion showed no significant hemolytic effect. Overall, the system showed suitable physicochemical characteristics and biocompatibility, with substantial in vitro antifungal activity, suggesting that this system can be further investigated for OC treatment.

An Inhalable Powder Formulation Based on Micro- and Nanoparticles Containing 5-Fluorouracil for the Treatment of Metastatic Melanoma.

Melanoma is the most aggressive and lethal type of skin cancer, with a poor prognosis because of the potential for metastatic spread. The aim was to develop innovative powder formulations for the treatment of metastatic melanoma based on micro- and nanocarriers containing 5-fluorouracil (5FU) for pulmonary administration, aiming at local and systemic action. Therefore, two innovative inhalable powder formulations were produced by spray-drying using chondroitin sulfate as a structuring polymer: (a) 5FU nanoparticles obtained by piezoelectric atomization (5FU-NS) and (b) 5FU microparticles of the mucoadhesive agent Methocel™ F4M for sustained release produced by conventional spray drying (5FU-MS). The physicochemical and aerodynamic were evaluated in vitro for both systems, proving to be attractive for pulmonary delivery. The theoretical aerodynamic diameters obtained were 0.322 ± 0.07 µm (5FU-NS) and 1.138 ± 0.54 µm (5FU-MS). The fraction of respirable particles (FR%) were 76.84 ± 0.07% (5FU-NS) and 55.01 ± 2.91% (5FU-MS). The in vitro mucoadhesive properties exhibited significant adhesion efficiency in the presence of Methocel™ F4M. 5FU-MS and 5FU-NS were tested for their cytotoxic action on melanoma cancer cells (A2058 and A375) and both showed a cytotoxic effect similar to 5FU pure at concentrations of 4.3 and 1.7-fold lower, respectively.