Development of purified cashew gum mucoadhesive buccal tablets containing nystatin for treatment of oral candidiasis.

OBJECTIVE: The objective of this work was to prepare mucoadhesive buccal tablets containing nystatin and purified cashew gum for the treatment of oral candidiasis. SIGNIFICANCE: Mucoadhesive buccal tablets containing the drug nystatin are an alternative to oral suspensions, which cause low therapeutic adherence to the treatment of oral candidiasis. Purified cashew gum has been studied as a diluent and mucoadhesive agent in tablets. METHODS: Two batches of mucoadhesive tablets were produced, MT1 and MT 2, containing purified cashew gum, nystatin (500,000 IU), flavoring agent and with or without the presence of lubricant agent. The average weight, mechanical properties, dose uniformity, drug release profile, mucoadhesive properties and antimicrobial activity against Candida albicans were evaluated. RESULTS: Tablets presented average weight of 329.1 ± 3.1 mg (MT1) and 334.6 ± 1.5 mg (MT2), hardness of 9.8 ± 0.8 KgF (MT1) and 8.3 ± 0.4 KgF (MT2), friability of 0.2% (MT1 and MT2), and dose uniformity of 102.20 ± 1.17% (MT1) and 99.06 ± 7.40% (MT2). MT1 and MT2 were able to swell, erode, release the drug and remain adhered to the pig's cheek up to 3 h for batch MT1 and 4 h for batch MT2, and the amount of nystatin released since the beginning of the test in both batches was sufficient to inhibit the growth of the fungus. CONCLUSIONS: Therefore, the proposed formulation proved to be very promising and met all the studied criteria, showing to be ideal for the treatment of oral candidiasis.

Multiple Response Optimization of Beeswax-Based Nanostructured Lipid Carriers for the Controlled Release of Vitamin E.

Consumer demand for cosmetics is growing, causing a need to develop new systems to release active ingredients. Among these, nanostructured lipid carriers (NLCs) have certain advantages regarding penetration of active compounds in the skin. The study reported here aimed to develop an NLC system for controlled release of vitamin E, a substance that has antioxidant and photoprotective properties. The NLCs containing vitamin E (NLC-VE) were prepared by the melting-emulsionsolidification method, using beeswax as the solid lipid, medium-chain triglycerides (MCTs), coconut oil or avocado oil as liquid lipids and three different nonionic surfactants. The composition of the system was defined by studying the effect of various experimental factors on the size distribution, average diameter and physical stability of the nanoparticles. The optimization of these characteristics, achieved by a Box-Behnken statistical design, showed that 8% w/w of the nonionic surfactant Tween 80, 24% ultrasound amplitude and processing time of 2 minutes and 16 seconds generated nanoparticles with homogeneous size (PDI = 0.11±0.02), average diameter of 180±20 nm and physical stability of 12 weeks. The NLC-VE systems prepared under the optimal conditions, containing Tween 80, beeswax and MCTs, were formulated as viscous suspensions by adding Pluronic F-127, a poly(ethylene oxide)-poly(propylene oxide) block copolymer, at a concentration of 10% w/w. The colloidal nanosuspension obtained had a viscosity of 222 mPa·s and released 70% of the active substance in 6 hours, indicating it is a promising candidate for controlled release of vitamin E.

Dual alginate-lipid nanocarriers as oral delivery systems for amphotericin B.

Amphotericin B (AmB) is the first-choice drug to treat several fungal infections. However, due to its low solubility it can only be administrated intravenously. Nanostructured lipid carriers (NLC) have the ability to encapsulate hydrophobic drugs in an aqueous matrix, making them interesting for use in alternative drug delivery systems for AmB. Their combination with stimuli-sensitive polymers such as alginate can be used as a strategy to protect acid sensitive molecules from gastric acid. The proposal of this work was to develop a dual-strategy hydrogel/NLC delivery system for amphotericin B. NLCs were produced by high-pressure homogenization and their size and stability were assessed by dynamic light scattering and electron transmission microscopy. The NLCs presented low cytotoxicity and high selectivity at neutral pH. Alginate hydrogels were successfully produced by the ionic gelation method and characterized using optical microscopy. The hydrogels were tested for their pH-selectivity, cytotoxicity and drug delivery profile. Swelling degree and drug delivery profiles suggested that drug delivery is stimulated as the alginate particles swell and that NLC particles maintain their structure even after rehydration, indicating these systems can be used for oral delivery of AmB.

Polymer-based Drug Delivery Systems Applied to Insects Repellents Devices: A Review.

Insects-borne diseases constitute a public health concern. Since there is no vaccine or curative treatment for many of these diseases, individual protection is the main approach to prevent them. Nowadays, the search for replacing synthetic molecules for insect repellents from natural sources, such as essential oils, is increasing. However, most of them present low efficiency compared to synthetic repellents. Therefore, decreasing skin permeation of synthetic repellents or yet, increasing effectiveness of natural repellents are challenges that must be overcome during the development of novel insect repellent formulations. In this context, polymer-based formulations allow entrapping active ingredients and provide release control. Encapsulation into polymeric micro/nanocapsules, cyclodextrins, polymeric micelles or hydrogels constitutes an approach to modify physicochemical properties of encapsulated molecules. Such techniques, applied in topical formulations, fabrics modification for personal protection, or food packaging have proved to be more effective in increasing repellency time and also in reducing drug dermal absorption, improving safety profiles of these products. In this work, the main synthetic and natural insect repellents are described as well as their polymeric carrier systems and their potential applications.

Development and characterization of micellar systems for application as insect repellents.

N,N-diethyl-meta-toluamide (DEET) is a widely used insect repellent due to its high efficacy. In this work, micellar systems based on poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymer were developed and studied for the purpose of controlling the release and cutaneous permeation of DEET, using concentrated solutions of the copolymer Pluronic F127 to form thermoreversible gels. The formulations presented thermoreversible gelation above 5°C and altered rheological behavior at 15 and 25°C. The presence of the drug drastically changed the sol-gel transition temperatures. The micrographs suggest that DEET induced the formation of anisotropic structures, and Maltese Crosses were observed. The formulation containing 10wt% DEET and 15wt% Pluronic F127 presented sustained drug release for up to 7h. DEET release profile followed the Higuchi kinetics model. There was a reduction of approximately 35% in the amount of DEET absorbed through the skin after 6h. About 62% of DEET from the formulation consisting of Pluronic F127 and DEET remain retained on the skin. The anisotropic structure may constitute a barrier to diffusion and thereby controlling the drug release effectively. These tests suggest that the tested samples exhibit safety profile greater than some commercially available products.

Characterization and evaluation of poly(epsilon-caprolactone) nanoparticles containing 2-ethylhexyl-p-methoxycinnamate, octocrylene, and benzophenone-3 in anti-solar preparations.

Ultraviolet radiation can bring both harm and benefits to human health. Among those harms are erythemas, photosensitivity, photoaging, and the most worrying, skin cancer. Nanoencapsulation of sunscreen agents (SA) by using a biocompatible and biodegradable polymer such as poly(epsilon-caprolactone) (PCL) is advantageous as it increases the retention of UV absorbers in the skin, avoids systemic absorption, and consequently, improves water resistance and stability of the preparation. The aim of this work is to develop, characterize, and study the encapsulation of 3 different SA: 2-ethylhexyl-p-methoxycinnamate, benzophenone-3, and octocrylene in PCL nanoparticles (Nps). Nps were prepared by the solvent emulsification and evaporation method. The process yield was calculated, and the Nps were characterized in terms of size, polydispersity index (PI), morphology, zeta potential (ZP), encapsulation efficiency (EE) (%), and sunscreen agent content (SAC). The final formulations were submitted to the hen's egg test-chorioallantoic membrane (HET-CAM), chorioallantoic membrane-trypan blue staining (CAM-TBS), red blood cell (RBC), Draize tests, in vitro release, in vitro sun protection factor (SPF), UVA protection factor (PF-UVA), and photostability. All the Nps were in the nanometric scale. PI showed monodisperse systems. ZP became more negative as the Np were lyophilized and were added to the formulations. EE varied from 84 to 90%. The SAC went from 44 to 65 microg of sunscreen agents by milligram of Np. The process yield went from 60 to 76%. Nps were predominantly spherical and elliptical forms. The addition of Np diminished the release of the SA. The SPF increased with Np presence and helped to maintain the PF-UVA after irradiation. The HET-CAM assay evaluated the formulation as slightly irritant, CAM-TBS and RBC tests as non irritant, and the Draize test as moderately irritant.