Preformulation and characterization of raloxifene-loaded lipid nanoparticles for transdermal administration.

Transdermal administration of raloxifene hydrochloride (RLX)-loaded nanostructured lipid carriers (NLCs) has been proposed to circumvent its low oral bioavailability (2%). Preformulation studies were carried out to evaluate drug-excipient compatibility of various adjuvants commonly used for NLC preparation (waxes, cholesterol, compritol, gelucire, span 60, span 80, span 85, tween 80, poloxamer 188, oleic acid, caprylic/capric triglyceride, and castor oil). It was used differential scanning calorimetry (DSC), isothermal stress testing (IST), and solubility studies. The most promising excipients were chosen for NLC obtention, and full characterization was done, including in vitro skin permeation. DSC curves suggested drug-excipient interaction among some compounds, and the IST study showed incompatibility of RLX with waxes, compritol, cholesterol, span 60, and poloxamer 188. Solubility studies helped select gelucire, caprylic/capric triglyceride, span 80, and tween 80 for NLC production. Twelve NLCs were obtained (NLC1 to NLC12), but NLC7 and NLC8 were the most promising ones. In vitro release studies demonstrated that NLC7 and NLC8 were able to control RLX release (14.74 and 9.07% at 24 h, respectively) compared with the unloaded drug (> 90% at 24 h). Unloaded RLX did not permeate the diffusion cells' receptor medium and showed higher drug skin retention (11-fold) than RLX-loaded NLC. NLC reduced RLX skin retention, favoring drug permeation to deeper skin layers. NLC7 increased drug flux is 2.4-fold. NLC7 is a promising formulation for RLX transdermal drug delivery.

Enhanced Skin Permeation of Punicalagin after Topical Application of Pluronic Micelles or Vesicles Loaded with Lafoensia pacari Extract.

Punicalagin, the principal ellagitannin of Lafoensia pacari leaves, has proven antioxidant activity, and standardized extracts of L. pacari can be topically used for skin aging management. We hypothesized that Pluronic nanomicelles or vesicles could solubilize sufficiently large amounts of the standardized extracts of L. pacari and provide chemical stability to punicalagin. The standardized extracts of L. pacari were obtained with an optimized extraction procedure, and the antioxidant activity was characterized. Formulations containing Pluronic at 25% and 35% were obtained with or without Span 80. They were characterized by average diameter, polydispersity index, punicalagin content, physicochemical stability, and rheology. A release and skin permeation study was carried out in vertical diffusion cells. The extraction procedure allowed quantifying high punicalagin content (i.e., 141.61 ± 3.87 mg/g). The standardized extracts of L. pacari showed antioxidant activity for all evaluated methods. Pluronic at 25 and Pluronic at 35 with standardized extracts of L. pacari showed an average diameter of about 25 nm. The addition of Span 80 significantly increased the mean diameter by 15-fold (p < 0.05), indicating the spontaneous formation of vesicles. Pluronic formulations significantly protected punicalagin from chemical degradation (p < 0.05). Pluronic at 25 formulations presented as free-flowing liquid-like systems, while Pluronic at 35 resulted in an increase of about 44-fold in |ƞ*|. The addition of Span 80 significantly reduced the Pluronic sol-gel transition temperature (p < 0.05), indicating the formation of vesicles. Formulations with Span 80 significantly enhanced punicalagin skin permeation compared to formulations without Span 80 (p < 0.05). Formulations with Span 80 were demonstrated to be the most promising formulations, as they allowed significant permeation of punicalagin (about 80 to 315 µg/cm2), which has been shown to have antioxidant activity.

SLN- and NLC-encapsulating antifungal agents: skin drug delivery and their unexplored potential for treating onychomycosis.

BACKGROUND: Lipid nanoparticles have been extensively studied for drug delivery of antifungal drugs, especially for dermatophytosis treatments. They can accumulate in skin appendages and release drugs in a controlled manner and also increase skin moisture, due to the formation of an occlusive film. Since moisture heavily influences nail and skin permeability, these systems seem to pose great potential for antifungal drug delivery. METHODS: We therefore compare skin and nail physiopathological structure and discuss the potential use of lipid nanoparticles in managing skin and nail mycoses, highlighting their unexplored use in onychomycosis. RESULTS: Structural features become particularly relevant when treating local skin/nail disorders. Nail plate represents the most resistant barrier to the penetration of molecules. In recent years, at least 55 researches have been reported about lipid nanoparticles and, antifungal drugs. They have focused on production methods and nanoparticle ingredients influence on entrapment efficiency, fungal activity in vitro, stability, and drug release. Lipid nanoparticles such as SLN and NLC have shown great results in permeating the skin. Currently, however, there is just one study published using NLC applied directly to the nail plate. NLC containing voriconazole had a noteworthy impact on the penetration depth of a nanoencapsulated drug, which allowed its deeper penetration into porcine hooves than the unloaded drug. CONCLUSION: Evidence of the success of SLN and NLC in achieving high encapsulation efficiencies of antifungals and promoting cutaneous delivery indicates the potential of the systems in enhancing nail hydration and drug penetration into the nail plate.

Development of a High-Performance Liquid Chromatographic Method for Asiaticoside Quantification in Different Skin Layers after Topical Application of a Centella asiatica Extract.

The topical application of Centella asiatica extract has been commonly used for many different purposes but especially for cosmetic use in the treatment of gynoid lipodystrophy. Asiaticoside, the most active component in this extract, is responsible for its therapeutic activities. However, little is known to date about asiaticoside skin penetration. Thus, an analytical method for asiaticoside quantification in different skin layers after the topical application of C. asiatica extract was developed and skin permeation studies were performed with the plant extract to apply the analytical method developed. An extraction procedure to recover asiaticoside from the biological matrix was also developed. Asiaticoside was assayed by HPLC/UV (high-performance liquid chromatography-ultraviolet detection) using a gradient of ACN (acetonitrile) and 0.2% phosphoric acid (flow rate of 1.0 mL/min). The analytical procedure was validated according to U. S. Food and Drug Administration guidelines. Selectivity was shown, as endogenous skin components did not interfere with the asiaticoside peak. Analytical curve was linear (3 to 60 µg/mL) and the lower limit of quantification was determined (3 µg/mL). Asiaticoside recoveries from skin samples were 95.1% and 66.7% for the stratum corneum and remaining skin, respectively. After 48 h of in vitro permeation studies, a substantial amount of asiaticoside was quantified in the skin layers. The presence of asiaticoside was also detected in the receptor solution of Franz diffusion cells after 48 h (5.81 ± 1.00 µg/mL). The method was reliable and reproducible for asiaticoside quantification in skin samples, thereby making it possible to determine the cutaneous penetration profile of this drug in permeation studies.