Development and evaluation of coenzyme Q10 loaded solid lipid nanoparticle hydrogel for enhanced dermal delivery

Coenzyme Q10 (Q10) loaded solid lipid nanoparticles (SLN) were prepared by the high speed homogenization method and incorporated into Carbopol 974P hydrogels. Compritol 888 ATO (C888) was employed as the lipid base Poloxamer 188 (P188) and Tween 80 (Tw80) were used as surfactant and co-surfactant. Optimum particle size with narrow distribution was obtained as 152.2 nm for blank and 142.4 nm for Q10 loaded SLNs. The overall charge of loaded SLNs was –13.7 ± 1.3 mV. Q10 entrapment efficiency was 89 % and the production yield was 94 %. Transmission electron microscopy analysis provided evidence of colloidal size, spherical shape while differential scanning calorimetry analysis confirmed re-crystallization of the lipid after preparation of SLNs. Trolox equivalent antioxidant capacity (TEAC) analysis has shown that antioxidant potential of Q10 can be protected in SLNs. Rheological characteristics demonstrated that the SLN incorporating gels were shear thinning and the mechanical strength of the gels was suitable for topical application. Diffusion studies from rat abdominal skin revealed that the delivery of Q10 was doubled in SLN incorporating gels, approximately 40 µg cm–2, in comparison with gels prepared with only Q10 (not incorporated in SLNs). As a result, it can be stated that Q10-SLN loaded gels can be successful delivery systems for carrying Q10 efficiently into the skin without losing its antioxidant properties

Resveratrol-loaded solid lipid nanoparticles versus nanostructured lipid carriers: evaluation of antioxidant potential for dermal applications

Evren H Gokce1, Emrah Korkmaz1, Eleonora Dellera2, Giuseppina Sandri2, M Cristina Bonferoni2, Ozgen Ozer11Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Ege, Izmir, Turkey; 2Department of Drug Sciences, University of Pavia, Pavia, ItalyBackground: 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.Keywords: solid lipid nanoparticles, nanostructured lipid carriers, resveratro

The Interaction of Oxidative Stress Response with Cytokines in the Thyrotoxic Rat: Is There a Link?

Oxidative stress is regarded as a pathogenic factor in hyperthyroidism. Our purpose was to determine the relationship between the oxidative stress and the inflammatory cytokines and to investigate how melatonin affects oxidative damage and cytokine response in thyrotoxic rats. Twenty-one rats were divided into three groups. Group A served as negative controls. Group B had untreated thyrotoxicosis, and Group C received melatonin. Serum malondialdehyde (MDA), glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx), and nitric oxide derivates (NO•x), and plasma IL-6, IL-10, and TNF-alpha were measured. MDA, GSH, NO•x, IL-10, and TNF-alpha levels increased after L-thyroxine induction. An inhibition of triiodothyronine and thyroxine was detected, as a result of melatonin administration. MDA, GSH, and NO•x levels were also affected by melatonin. Lowest TNF-alpha levels were observed in Group C. This study demonstrates that oxidative stress is related to cytokine response in the thyrotoxic rat. Melatonin treatment suppresses the hyperthyroidism-induced oxidative damage as well as TNF-alpha response

New FIP resources to advance pharmacy education and early career development

During the COVID-19 pandemic, FIP Education (FIPEd) continued to produce reports, guidance documents, toolkits, and virtual programmes to advance pharmacy education and early career development.peer-reviewe

Fabrication of Montelukast sodium loaded filaments and 3D printing transdermal patches onto packaging material

WOS: 000568780600012PubMed: 32663585The main objectives of this work were to develop and characterize new 3D printing filaments and print them directly onto a packaging material. Different blends of polymers were tested to achieve low-temperature printing filaments, which are flexible and durable to be wound onto spools. the mechanical properties of filaments were compared with commercial filaments and evaluated by bending tests. Kollidon 12PF, PEG 4000, and PEO 900k blends resulted in promising filaments that could be extruded at 70 degrees C and had flexibility similar to commercial PLA filaments. Montelukast sodium (MS), which undergoes hepatic first-pass metabolism, was compounded into polymer blends, and drug-loaded filaments were extruded. All filaments were tested with a 3D printing pen prior to using with the 3D printer for transdermal patches. MS loaded filaments and patches showed similar flexibility with placebo. in vitro drug release studies showed 52% of MS was released in 24 h. Printing on disposable packaging material is presented for the first time with this study. Build plate adhesion and cohesion of 3D printed layers were successfully achieved. This new technique could prevent cross-contamination, save time, and provide ease of use, which can take us one step closer to the production of personalized drugs in pharmacies.Scientific and Technological Research Council of Turkey-TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [214M077]This work was supported by the Scientific and Technological Research Council of Turkey-TUBITAK (Project number: 214M077). Special thanks to Dr. Richard Terry for his support, proof-reading, and constructive discussions

Fabrication of pure-drug microneedles for delivery of montelukast sodium

Dissolving microneedle (MN) patches are usually formulated with a blend of drug and excipients added for mechanical strength and drug stabilization. In this study, we developed MNs made of pure drug to maximize drug loading capacity. MN patches were fabricated for transdermal delivery of montelukast sodium (MS) which is used to treat asthma and allergic rhinitis. We developed three different fabrication methods - solvent casting, melt casting, and solvent washing - and determined that filling molds with MS powder followed by a solvent washing method enabled MS to be loaded selectively to the MNs. Drug localization was confirmed with Raman imaging. MNs were able to penetrate in vitro and ex vivo skin models, and maintained strong mechanical properties during 6 months' storage at 22 degrees C. MS was also stable and compatible with the formulation used for the patch backing layer after 3 months' storage at 40 degrees C. MS delivery efficiency into skin was 55%, which enabled delivery of 3.2 mg MS into porcine skin ex vivo, which is in the range of MS doses in human clinical use. We conclude that the solvent washing method can be used to prepare MNs containing pure drug, such as MS at milligram doses in a similar to 1 -cm(2) MN patch.Scientific and Technological Research Council of Turkey-TUBITAK (2214-A-International Research Fellowship Programme for PhD Students)This work was supported by The Scientific and Technological Research Council of Turkey-TUBITAK (2214-A-International Research Fellowship Programme for PhD Students)