Medicated lacquer for application on adornments to treat affections in aesthetic perforations.

Aesthetic perforations are often associated with health issues, such as itching, inflammation, or microbial infection. Accordingly, this work proposed a lacquer to be applied on the adornment accessory forming a film from which a proper drug is released. For this, lacquers were formulated containing three different permeation enhancers (limonene - LIM, propylene glycol - PG, and oleic acid - AO) combined according to a mixture design with a model anti-inflammatory natural drug (naringenin) and a soluble film-former polymer (polyvinyl alcohol). Formulations were characterized by physicochemical tests and in vitro and in vivo skin permeation studies. The lacquers were stable and provided a vectorized drug release. LIM, combined with one of the other permeation enhancers, showed a synergic effect, enhancing topical skin penetration in vitro by 53% while preventing permeation to the receptor medium. The in vivo evaluation of lacquers in rodent models showed these systems could provide higher levels of drug retention in the ear (166.4 ± 14.9 µg per ear for F4 and 174.9 ± 29.3 µg per ear for F5) compared to the control (109.2 ± 16.3 µg) without allowing its permeation into the bloodstream, confirming the local drug delivery. Moreover, the anti-inflammatory activity was achieved in the animal model developed for lacquer application on the earring, obtaining inhibition of ear swelling up to 40.8% ± 2.3 compared to the untreated ear. Thus, such an innovative lacquer proved a promising vehicle for treating affections caused by adornments, enhancing skin permeation while avoiding a systemic effect.

Transfersomes as alternative topical nanodosage forms for the treatment of skin disorders.

Topical drug delivery is a promising approach to treat different skin disorders. However, it remains a challenge mainly due to the nature and rigidity of the nanosystems, which limit deep skin penetration, and the unsuccessful demonstration of clinical benefits; greater penetration by itself, does not ensure pharmacological success. In this context, transfersomes have appeared as promising nanosystems; deformability, their unique characteristic, allows them to pass through the epidermal microenvironment, improving the skin drug delivery. This review focuses on the comparison of transfersomes with other nanosystems (e.g., liposomes), discusses recent therapeutic applications for the topical treatment of different skin disorders and highlights the need for further studies to demonstrate significant clinical benefits of transfersomes compared with conventional therapies.

Emerging Technologies to Target Drug Delivery to the Skin - the Role of Crystals and Carrier-Based Systems in the Case Study of Dapsone.

Dapsone (DAP) is a long-established molecule that remains a promising therapeutic agent for various diseases mainly because it combines antimicrobial and anti-inflammatory activities. Its oral application, however, is limited by the dose-dependent hematological side effects that may rise from systemic exposure. As an alternative to overcome this limitation, the administration of DAP to the skin has witnessed prominent interest in the past 20 years, particularly when applied to the treatment of dermatological disorders. In this review, all technological strategies proposed to the topical delivery of DAP are presented. Most of the reported studies have been devoted to the clinical use and safety of a gel formulation containing both solubilized and microcrystalline drug, however, the technological characteristics of such preparation are still missing. In parallel, the incorporation of DAP into vesicular and particulate carriers (e.g. nano- and microemulsions, niosomes, invasomes, bilosomes, cubosomes, solid lipid nanoparticles, nanostructured lipid carriers, polymeric nanocapsules and polymer-lipid-polymer hybrid nanoparticles) appears to be an alternative to provide greater drug release control, enhanced drug solubilization and follicular targeting. Indeed, the main application of DAP topical formulations reported in the literature was the treatment of acne vulgaris, a disease located in the hair follicle. Other diseases affecting different regions of the skin (e.g. cutaneous lupus erythematosus and cutaneous leishmaniasis), however, may also benefit from a topical therapeutic regimen containing DAP. Therefore, the investigation of appendageal route in comparison to passive transmembrane diffusion as a function of targeted disease, as well as pharmacokinetic studies, are perspectives highlighted herein. Such studies may drive future efforts towards the rational development of safe and effective technologies to deliver DAP to the skin. Graphical abstract.

Advances in lyotropic liquid crystal systems for skin drug delivery.

INTRODUCTION: Lyotropic liquid crystals (LLCs) are organized mesophases with intermediate properties between liquids and solids. The LLC and its liquid crystalline nanoparticles (LCNPs) have attracted great interest from the scientific community in recent years as potential drug delivery systems due to the high internal ordering and symmetry with a wide interfacial area. AREAS COVERED: This article aims to gather information and to provide a description of the highly organized structures of LLCs. Updates on production methods and new insights for LCNPs optimization and physico-chemical and morphological caracterization techniques were discussed. We also discussed why these systems proved to be a platform for the design of nanocarrier drug delivery, with an emphasis on topical and transdermal applications. EXPERT OPINION: Drug delivery platforms are of particular importance to improve the biopharmaceutical aspects of therapies topically. Although several systems can be used, LLC or LCNPs appear to be favored due to their similarity to the lipid structure of the skin. The highly ordered structure and the possibility of chemical modifications make it possible to obtain better clinical responses. The results of several studies support the innovations in this field and predict that these systems can innovate the market of technologies for the treatment of cutaneous diseases and cosmetology.

Formulation and Evaluation of a Novel Itraconazole-Clotrimazole Topical Emulgel for the Treatment of Sporotrichosis.

In recent years, the development of new pharmaceutical formulations for the treatment of sporotrichosis has become a relevant research field. In this work, we aimed to develop an emulgel containing itraconazole and clotrimazole to ensure therapeutic effectiveness against Sporothrix brasiliensis. The topical use of a formulation that combines both drugs represents an interesting option for the complementary treatment of sporotrichosis. The emulgel formulation was prepared and evaluated for its zeta potential, viscosity, in vitro antifungal activity and stability at different storage conditions. The results showed that the newly developed emulgel displayed promising physicochemical characteristics, as well as a good in vitro inhibitory activity against S. brasiliensis yeasts. The results obtained in this work suggest that the emulgel containing itraconazole and clotrimazole might highly be efficient and a complementary therapy to oral administration in the treatment of sporotrichosis.

Preparation and characterization of naftifine-loaded poly(vinyl alcohol)/sodium alginate electrospun nanofibers

In this study, naftifine (a topical antifungal drug) loaded poly(vinyl) alcohol (PVA)/sodium alginate (SA) nanofibrous mats were prepared using the single-needle electrospinning technique. The produced nanofibers were crosslinked with glutaraldehyde (GTA) vapor. The morphology and diameter of the electrospun nanofibers were studied by scanning electron microscopy (SEM). SEM images showed the smoothness of the nanofibers and indicated that the fiber diameter increased with crosslinking and drug loading. Atomic force microscopy (AFM) images confirmed the uniform production of the scaffolds, and elemental mapping via energy dispersive X-ray spectroscopy (EDS) showed the uniform distribution of the drug within the nanofibers. An attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy study demonstrated that naftifine has sufficient secondary interactions with the polymer blend. The crosslinking treatment decreased the burst drug release effectively and the release mechanism followed Korsmeyer-Peppas Super Case-II transport. Overall, these findings suggest the potential use of naftifine-loaded PVA/SA nanofibers as a topical antifungal drug delivery system.

Controlled Thermoreversible Formation of Supramolecular Hydrogels Based on Poly(vinyl alcohol) and Natural Phenolic Compounds.

Supramolecular hydrogels have promising applications in a wide variety of fields including 3D bioprinting, sensors and actuators, biomedicine, and controlled drug delivery. This communication reports the facile reversible thermotriggered formation of novel pH-responsive supramolecular hydrogels based on poly(vinyl alcohol) (PVA) bonded via dynamic H-bridge with small phenolic biomolecules. PVA and phenolic compounds form a clear solution when they are physically mixed in water at high temperature, but a fast gelation is produced at room temperature through multiple strong H-bonding interactions. The structure and type of functional groups of different phenolic molecules allow preparing hydrogels with tailor-made viscoelastic properties, controlled low phase transition temperature, and pH-dependent swelling behavior. This combination makes these supramolecular networks very interesting candidates to be used in 3D bioprinting and topical drug delivery of thermolabile biomolecules.

Nanotechnological Advances for Cutaneous Release of Tretinoin: An Approach to Minimize Side Effects and Improve Therapeutic Efficacy.

BACKGROUND: The clinical efficacy of the topical tretinoin is widely studied and has been well established for many therapeutic interventions, among some, photoaging, acne, and melasma. However, the side effects, mainly cutaneous irritation, erythema, xerosis and peeling, remain major obstacle to the patient compliance. Besides, the insight regarding the drug delivery profile is essential to understand the therapeutic action of the drug. METHODS: Through bibliographic research in databases we highlight further advances and an update on tretinoin delivery systems such as liposomes, niosomes, solid lipid nanoparticles, nanostructured lipid carriers, cyclodextrins, nanostructured polymers and other technological systems that reduce its side effects and improve the permeation profile to potentiate efficacy and drug safety on the skin. RESULTS: Pharmaceutical preparations were developed and evaluated for permeability in in vitro models using pig ear, snake, mouse and human skin, and potential for irritation was also verified using release systems for tretinoin and compared to available commercial formulations. Overall results indicated the composition, charge and size of the system influences the tretinoin delivery, modulating the type of release and its retention. Small unilamellar vesicles promoted greater cutaneous delivery of tretinoin. Negative charge, for both liposomes and niosomes, can improve pig skin hydration as well as the tretinoin retention. The quantity of solid lipids and the type of oil used in the composition of solid lipid nanoparticles and nanostructured lipid carriers affected percutaneous drug delivery. CONCLUSION: As evident from the literature, the tretinoin technological delivery systems consist an innovative and potential management for increasing the patient compliance presenting safety and efficacy.

Polyacrylic acid polymers hydrogels intended to topical drug delivery: preparation and characterization.

CONTEXT: Bioadhesiviness of polyacrylic acid polymers make them promising hydrogels to design topical drug delivery systems, allowing a close contact with biological substrate as well as an enhanced local concentration gradient, both factors that may improve the biological performance of the drugs. AIM: Texture and bioadhesive properties of hydrogels were assessed by using texture analyzer and they were correlated with their rheological behavior and performance as drug delivery systems. METHODS: Aqueous dispersions of both polymers were prepared at 0.5%, 1.0% and 1.5% w/v. Hardness, compressibility, adhesiveness, cohesiveness, bioadhesion, continuous flow, oscillatory dynamic test and in vitro drug release were evaluated. RESULTS: Rheological and texture parameters were dependent on polymer concentration and C974P polymer built the strongest structures. Both 1.5% hydrogels presented high bioadhesion values. About 50% of the metronidazole (MTZ) was sustained released from hydrogels within 2 h with an initial burst release at early stage. After, the release rates were decreased and 10% of the MTZ was released in the next 10 h. The drug release process was driven by Fickian diffusion and complex mechanism for PP and C974P hydrogels, respectively. CONCLUSION: The set of results demonstrated that these hydrogels are promising to be used as topical controlled drug delivery system.