Organogels (ORGs) are semi-solid materials, in which an organic phase is immobilized by a three-dimensional network composed of self-organized system, forming the aqueous phase. In this context, lipid–Pluronics (PLs) ORGs form a two-phase system which can be effectively used as skin delivery systems, favoring their permeation across the skin. In this study, we presented the development of ORG skin drug-delivery systems for curcumin (CUR), a liposoluble phenolic pigment extracted from the turmeric rhizome. In special, we designed the formulation compositions in order to carry high amounts of CUR soluble in oleic acid (OA), as organic phase, entrapped into an aqueous phase composed of micellar PL-based hydrogels by associating two polymers with different hydrophilic–lipophilic balances, Pluronic F-127 (PL F-127), and Pluronic L-81 (PL L-81), to enhance the permeation across the skin. Results revealed that the incorporation of PL L-81 favored the CUR incorporation into micelle–micelle interface. CUR insertion into OA-PL F-127/L-81 reduced both G’/G” relationship (∼16 x) and viscosity values (η* ∼ 54 mPa.s, at 32.5°C), disturbing the ORG network structural organization. In vitro permeation assays through Strat-M® skin-model membranes showed that higher CUR-permeated amounts were obtained for OA-PL F-127/L-81 (4.83 µg.cm−2) compared to OA-PL F-127 (3.51 μg.cm−2) and OA (2.25 μg.cm−2) or hydrogels (∼1.2 μg.cm−2, p < 0.001). Additionally, ORG formulations presented low cytotoxic effects and evoked pronounced antileishmanial activity (IC50 < 1.25 µg.ml−1), suggesting their potential use as skin delivery systems against Leishmania amazonensis. Results from this study pointed out OA-PL-based ORGs as promising new formulations for possible CUR topical administration.
Organogels (ORGs) are remarkable matrices due to their versatile chemical composition and straightforward preparation. This study proposes the development of ORGs as dual drug-carrier systems, considering the application of synthetic monoketonic curcuminoid (m-CUR) and lidocaine (LDC) to treat topical inflammatory lesions. The monoketone curcuminoid (m-CUR) was synthesized by using an innovative method via a NbCl5–acid catalysis. ORGs were prepared by associating an aqueous phase composed of Pluronic F127 and LDC hydrochloride with an organic phase comprising isopropyl myristate (IPM), soy lecithin (LEC), and the synthesized m-CUR. Physicochemical characterization was performed to evaluate the influence of the organic phase on the ORGs supramolecular organization, permeation profiles, cytotoxicity, and epidermis structural characteristics. The physico-chemical properties of the ORGs were shown to be strongly dependent on the oil phase constitution. Results revealed that the incorporation of LEC and m-CUR shifted the sol-gel transition temperature, and that the addition of LDC enhanced the rheological G′/G″ ratio to higher values compared to original ORGs. Consequently, highly structured gels lead to gradual and controlled LDC permeation profiles from the ORG formulations. Porcine ear skin epidermis was treated with ORGs and evaluated by infrared spectroscopy (FTIR), where the stratum corneum lipids were shown to transition from a hexagonal to a liquid crystal phase. Quantitative optical coherence tomography (OCT) analysis revealed that LEC and m-CUR additives modify skin structuring. Data from this study pointed ORGs as promising formulations for skin-delivery.
Dengue, yellow fever, Chinkungunya, Zika virus, and West Nile fever have infected millions and killed a considerable number of humans since their emergence. These arboviruses are transmitted by mosquito bites and topical chemical repellents are the most commonly used method to protect against vector arthropod species. This study aimed to develop a new generation of repellent formulations to promote improved arboviruses transmission control. A repellent system based on polycaprolactone (PCL)-polymeric nanoparticles was developed for the dual encapsulation of IR3535 and geraniol and further incorporation into a thermosensitive hydrogel. The physicochemical and morphological parameters of the prepared formulations were evaluated by dynamic light scattering (DLS), nano tracking analysis (NTA), atomic force microscopy (AFM). In vitro release mechanisms and permeation performance were evaluated before and after nanoparticles incorporation into the hydrogels. FTIR analysis was performed to evaluate the effect of formulation epidermal contact. Potential cytotoxicity was evaluated using the MTT reduction test and disc diffusion methods. The nanoparticle formulations were stable over 120 days with encapsulation efficiency (EE) of 60% and 99% for IR3535 and geraniol, respectively. AFM analysis revealed a spherical nanoparticle morphology. After 24 h, 7 ± 0.1% and 83 ± 2% of the GRL and IR3535, respectively, were released while the same formulation incorporated in poloxamer 407 hydrogel released 11 ± 0.9% and 29 ± 3% of the loaded GRL and IR3535, respectively. GRL permeation from PCL nanoparticles and PCL nanoparticles in the hydrogel showed similar profiles, while IR3535 permeation was modulated by formulation compositions. Differences in IR3535 permeated amounts were higher for PCL nanoparticles in the hydrogels (36.9 ± 1.1 mg/cm2) compared to the IR3535-PCL nanoparticles (29.2 ± 1.5 mg/cm2). However, both active permeation concentrations were low at 24 h, indicating that the formulations (PCL nanoparticles and PCL in hydrogel) controlled the bioactive percutaneous absorption. Minor changes in the stratum corneum (SC) caused by interaction with the formulations may not represent a consumer safety risk. The cytotoxicity results presented herein indicate the carrier systems based on poly-epsilon caprolactone (PCL) exhibited a reduced toxic effect when compared to emulsions, opening perspectives for these systems to be used as a tool to prolong protection times with lower active repellent concentrations.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.