ABSTRACT
The aim of this work was to prepare organogels of Carbopol 974P NF (C974) in PEG 400 by using a novel technique, high-speed homogenization followed by microwave heating. Triclosan (TCS) was used as a model drug. C974, at concentrations ranging between 2% and 4%, was dispersed in 25 ml of PEG 400, and the dispersion was homogenised for 5 min at 24,000 rpm. The dispersion was either heated at 80°C in water bath under mechanic stirring at 200 rpm or exposed to micro-irradiation (1,200 W/1 h) for 2 min. The formulations prepared with both methods performed a well-structured gel matrix characteristic at 3% and 4% of C974 concentrations. As the concentrations of the polymer increased, the elastic properties also increased. The viscosity profiles indicated a shear-thinning system. DSC data revealed that TCS was dissolved in gel. Skin accumulation ability of TCS had been improved by these novel organogels regardless of the preparation method. TCS was still microbiologically effective after the microwave process was applied. It was determined that microwave heating is a suitable method to obtain C974 organogels. This novel production technique developed might be promising especially in industrial scale when the dramatic reduction in the preparation time and energy were considered.
Subject(s)
Gels , Organic Chemicals , Calorimetry, Differential Scanning , Magnetic Resonance Spectroscopy , Rheology , Skin/metabolismABSTRACT
BACKGROUND: The effective delivery of coenzyme Q10 (Q10) to the skin has several benefits in therapy for different skin pathologies. However, the delivery of Q10 to deeper layers of skin is challenging due to low aqueous solubility of Q10. Liposomes and solid lipid nanoparticles (SLN) have many advantages to accomplish the requirements in topical drug delivery. This study aims to evaluate the influence of these nanosystems on the effective delivery of Q10 into the skin. METHODS: Q10-loaded liposomes (LIPO-Q10) and SLNs (SLN-Q10) were prepared by thin film hydration and high shear homogenization methods, respectively. Particle size (PS), polydispersity index (PI), zeta potential (ZP), and drug entrapment efficiency were determined. Differential scanning calorimetry analysis and morphological transmission electron microscopy (TEM) examination were conducted. Biocompatibility/cytotoxicity studies of Q10-loaded nanosystems were performed by means of cell culture (human fibroblasts) under oxidative conditions. The protective effect of formulations against production of reactive oxygen species were comparatively evaluated by cytofluorometry studies. RESULTS: PS of uniform SLN-Q10 and LIPO-Q10 were determined as 152.4 ± 7.9 nm and 301.1 ± 8.2 nm, respectively. ZPs were -13.67 ± 1.32 mV and -36.6 ± 0.85 mV in the same order. The drug entrapment efficiency was 15% higher in SLN systems. TEM studies confirmed the colloidal size. SLN-Q10 and LIPO-Q10 showed biocompatibility towards fibroblasts up to 50 µM of Q10, which was determined as suitable for cell proliferation. The mean fluorescence intensity % depending on ROS production determined in cytofluorometric studies could be listed as Q10 ≥ SLN-Q10 > LIPO-Q10. CONCLUSION: The LIPO-Q10 system was able to enhance cell proliferation. On the contrary, SLN-Q10 did not show protective effects against ROS accumulation. As a conclusion, liposomes seem to have advantages over SLN in terms of effective delivery of Q10 to skin for antioxidant purposes.
Subject(s)
Fibroblasts/metabolism , Lipids/chemistry , Liposomes/chemistry , Nanocapsules/chemistry , Skin Absorption/physiology , Ubiquinone/analogs & derivatives , Administration, Topical , Antioxidants/administration & dosage , Antioxidants/pharmacokinetics , Cell Line , Humans , Nanocapsules/administration & dosage , Ubiquinone/administration & dosage , Ubiquinone/pharmacokineticsABSTRACT
BACKGROUND: Excessive generation of radical oxygen species (ROS) is a contributor to skin pathologies. Resveratrol (RSV) is a potent antioxidant. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) can ensure close contact and increase the amount of drug absorbed into the skin. In this study, RSV was loaded into SLN and NLC for dermal applications. METHODS: Nanoparticles were prepared by high shear homogenization using Compritol 888ATO, Myglyol, Poloxamer188, and Tween80. Particle size (PS), polydispersity index (PI), zeta potential (ZP), drug entrapment efficiency (EE), and production yield were determined. Differential scanning calorimetry (DSC) analysis and morphological transmission electron microscopy (TEM) examination were conducted. RSV concentration was optimized with cytotoxicity studies, and net intracellular accumulation of ROS was monitored with cytofluorimetry. The amount of RSV was determined from different layers of rat abdominal skin. RESULTS: PS of uniform RSV-SLN and RSV-NLC were determined as 287.2 nm ± 5.1 and 110.5 nm ± 1.3, respectively. ZP was -15.3 mV ± 0.4 and -13.8 mV ± 0.1 in the same order. The drug EE was 18% higher in NLC systems. TEM studies showed that the drug in the shell model was relevant for SLN, and that the melting point of the lipid in NLC was slightly lower. Concentrations below 50 µM were determined as suitable RSV concentrations for both SLN and NLC in cell culture studies. RSV-NLC showed less fluorescence, indicating less ROS production in cytofluorometric studies. Ex vivo skin studies revealed that NLC are more efficient in carrying RSV to the epidermis. CONCLUSION: This study suggests that both of the lipid nanoparticles had antioxidant properties at a concentration of 50 µM. When the two systems were compared, NLC penetrated deeper into the skin. RSV-loaded NLC with smaller PS and higher drug loading appears to be superior to SLN for dermal applications.
