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

Perillyl alcohol in Solid Lipid Nanoparticles (SLN-PA): Cytotoxicity and antitumor potential in sarcoma 180 mice model

Cancer is a group of diseases characterized by the uncontrolled growth of cells. These cells invade organs and tissues by extension or direct dissemination and can spread to other regions of the body. Nanomedicine offers many possibilities to prevent the spread of cancer tissue and help cure the disease. In this work, solid lipid nanoparticles (SLN) were used to encapsulate perillyl alcohol (PA), a volatile monoterpene with proven anticancer activity. Encapsulation of PA into SLN (SLN-PA) is expected to promote controlled release, increase PA bioavailability, and impair the volatility of the monoterpene. SLN-PA prepared by high-shear homogenization showed average particle diameter around 254 nm, polydispersity index ~ 0.35, zeta potential ~ -14.7 mV, and encapsulation efficiency 84.6%. Scanning electron microscope analysis revealed a decrease in crystallinity, suggesting the encapsulation of PA in the SLN, confirming the spherical shape and the loading of the monoterpene in the SLN. In vitro cytotoxicity assays against murine fibroblasts (L929) showed that SLN-PA in both treated doses did not induce any cytotoxicity on non-tumoral cells. In vivo antitumor effect of the SLN-PA was evaluated in sarcoma 180-transplanted mice. The in vivo results demonstrated a significant tumor inhibition rate of 51.76 and 54.49% via intraperitoneal application of SLN-PA at doses of 100 and 200 mg/kg/day (p < 0.05), respective when compared to the negative control (dimethyl sulfoxide). Adverse side effects of SLN-PA were not noticed in the liver, the kidney, or spleen tissue. The developed SLN-PA can be considered as a safe approach for site-specific antitumor effect in vivo, reinterpreting new nanoparticles- based cancer therapy.This work was supported by the Banco do Nordeste (grant FUNDECI/2016.0015), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Apoio à Pesquisa e à Inovação Tecnológica do Estado de Sergipe (Fapitec) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). Eliana B. Souto would like to acknowledge the Portuguese Science and Technology Foundation (FCT/MCT) and from European Funds (PRODER/COMPETE) for the project UIDB/04469/2020 (strategic fund), co-financed by FEDER, under the Partnership Agreement PT2020.info:eu-repo/semantics/publishedVersio

An Optimization Study on Solid Lipid Nanoparticles Using Artificial Neural Network

WOS: 000399260300016Common use of supportive programs in finding the best in R&D studies provides positive results and thus ensures benefits to companies in terms of cost and time. The aim of this work was to develop, evaluate and optimize solid lipid nanoparticles (SLNs) formulations by applying the artificial neural network (ANN) programme to achieve the best combination of materials. SLNs have been produced by high-pressure homogenization, and the formulations have been characterized for their mean particle size, polydispersity index and zeta potential. SLN formulations were evaluated with INForm V5.1 program to optimize the best-fit formulation. According to ANN evaluation, S-PT8 formulation including 50% Compritol 888 ATO, 38% Poloxamer 188 and 12% Tween 80 mixture was found to be the most promising formulation in terms of parameters tested. It has been shown that artificial intelligence could be used to improve our understanding of the critical quality parameters that contribute to the overall quality of the drug product.TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [112S292]This study was supported by TUBITAK Projects No: 112S292. The authors would like to thank to Ege University, Faculty of Pharmacy, Pharmaceutical Sciences Research Center (FABAL)

Evaluation of characteristics and in vitro antioxidant properties of RSV loaded hyaluronic acid-DPPC microparticles as a wound healing system

WOS: 000350918900007PubMed ID: 25543983Resveratrol (RSV) was incorporated into microparticles by spray drying to treat chronic wounds such as diabetic ulcers. RSV was chosen due to its defense mechanisms as the formation of free radicals delays the healing process. RSV was loaded into microparticles consisting of dipalmitoylphosphatidylcholine (DPPC) and hyaluronic acid (HA), a polysaccharide naturally present within the skin, known to contribute to the healing process. Microparticles were evaluated in terms of production yield, size distribution, encapsulation efficiency, morphology, specific surface area, thermal properties and water content. Spherical and homogenous microparticles (span = 97%). The effect of enzymes (hyaluronidase, phospholipase and lipase) on RSV release showed a dose-dependent pattern followed by a slow release stage. Cytotoxicity/proliferation and oxidative stress parameters (glutathione, oxidized glutathione, glutathione peroxidase, malondialdehyde, superoxide dismutase) obtained from human dermal fibroblast cell cultures revealed that formulations increased cell proliferation and the presence of RSV decreased oxidation in cells. RSV-loaded HA-DPPC microparticles appear as a promising formulation for wound healing due to synergistic effect of the ingredients. (C) 2014 Elsevier B.V. All rights reserved.Scientific and Technological Research Council of Turkey-TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [111S183]The authors would like to thank Prof. Dr. Hande Gurer Orhan from Ege University, Faculty of Pharmacy, Department of Toxicology for cytotoxicity studies and Ege University, Faculty of Pharmacy, Pharmaceutical Sciences Research Center (FABAL) for thermal analysis facilities. This work was supported by The Scientific and Technological Research Council of Turkey-TUBITAK (Project number: 111S183)

Wound healing effects of collagen-laminin dermal matrix impregnated with resveratrol loaded hyaluronic acid-DPPC microparticles in diabetic rats

WOS: 000412041500003PubMed ID: 28461085An alternative formulation for the treatment of diabetic foot wounds that heal slowly is a requirement in pharmaceutical field. The aim of this study was to develop a dermal matrix consisting of skin proteins and lipids with an antioxidant that will enhance healing and balance the oxidative stress in the diabetic wound area due to the high levels of glucose. Thus a novel three dimensional collagen-laminin porous dermal matrix was developed by lyophilization. Resveratrol-loaded hyaluronic acid and dipalmitoylpho sphatidylcholine microparticles were combined with this dermal matrix. Characterization, in vitro release, microbiological and in vivo studies were performed. Spherical microparticles were obtained with a high RSV encapsulation efficacy. The microparticles were well dispersed in the dermal matrix from the surface to deeper layers. Collagenase degraded dermal matrix, however the addition of RSV loaded microparticles delayed the degradation time. The release of RSV was sustained and reached 70% after 6 h. Histological changes and antioxidant parameters in different treatment groups were investigated in full-thickness excision diabetic rat model. Collagen fibers were intense and improved by the presence of formulation without any signs of inflammation. The highest healing score was obtained with the dermal matrix impregnated with RSV-microparticles with an increased antioxidant activity. Collagenlaminin dermal matrix with RSV-microparticles was synergistically effective due to presence of skin components in the formulation and controlled release achieved. This combination is a safe and promising option for the treatment of diabetic wounds requiring long recovery. (C) 2017 Elsevier B.V. All rights reserved.TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [1113183]; Ege University Technology Transfer Office [WO/2015/012775 A1]; ANRFrench National Research Agency (ANR) [ANR-10-LABX-33]This work was supported by TUBITAK 1001 [No: 1113183] and by Ege University Technology Transfer Office for patenting issues [Patent No: WO/2015/012775 A1]. Authors would like to thank FABAL for DSC facilities and Prof. Dr. Mine Hosgor Limoncu (Ege University Faculty of Pharmacy, Department of Microbiology) for sterility evaluation studies and Valerie Nicolas (Plateforme Imagenie Cellulaire, UMS IPSIT (Institut Paris Saclay d'Innovation Therapeutique), Univ. Paris-Sud, Universite Paris-Saclay) for her help with confocal microscopy. Institut Galien Paris-Sud is a member of the Laboratory of Excellence LERMIT supported by a grant from ANR (ANR-10-LABX-33)

Health transformation project and defensive medicine practice among neurosurgeons in Turkey.

The term "Defensive" medicine was coined in the early 1970's and has been an important topic of scientific investigation and professional debate ever since.The aim of this study was to investigate the characteristics of defensive medicine, its reasons, and the extent to which it is practiced in the Turkish health care system. This is the first national survey to study the practice of defensive medicine among neurosurgeons in Turkey.The present cross-sectional study on defensive medicine assessed neurosurgeons registered at the Turkish Neurosurgical Society, who are actively working in various centers and hospitals within the Turkish health care system. A 40-question survey was adapted from existing measures described in the literature and was completed by a total of 404 neurosurgeons, representing 36.7% of the neurosurgeons registered at the Turkish Neurosurgical Society.Seventy-two percent of the participants in the current study reported practicing defensive medicine. This practice was mainly reported among inexperienced neurosurgeons (74.4%). Most were younger than 40 years of age (75.2%), working in state hospitals/universities (72.7%), and living in the Marmara region (38%). Respondents reported engaging in defensive medicine by avoiding high-risk surgery (62.6%), ordering additional imaging studies (60.9%) and laboratory tests (33.7%), and referring patients to consultants (31.2%). Most participants consider every patient as a potential threat in terms of a medical lawsuit (68.3%) and do not believe the courts can distinguish malpractice from complications (89.6%).Concerns and perceptions about medical liability lead neurosurgeons to practice defensive medicine. By avoiding high-risk surgery, ordering unnecessary diagnostic tests, and referring the patients to consultants, neurosurgeons try to minimize the risk of malpractice and protect themselves from legal risks, resulting in higher healthcare expenditure and longer treatment periods