Physicochemical properties of nanostructured lipid carriers as colloidal carrier system stabilized with polysorbate 20 and polysorbate 80

Nanostructured lipid carriers (NLC), a colloidal carrier system offer many advantages as drug carrier. Incorporation of liquid lipid can improve the loading capacity of drugs in the NLCs. The NLC20 and NLC80 were produced by high-pressure homogenization technique, stabilized with polysorbate 20 and polysorbate 80, respectively. Transmission electron microscopy showed that these NLCs were spherical. Photon correlation spectroscopy showed that the average size of NLC80 and NLC20 were102.8 ± 0.1 and 261.63 ± 8.56 nm, respectively, and their zeta potentials were -23.93 ± 0.75 and -30.57 ±0.06 mV, respectively. The results suggest that NLC80 is a more stable formulation. X-ray diffractometryand differential scanning calorimetry showed that NCLs were less crystalline than the bulk lipid. The melting point depression of NLC80 was 5.71°C below bulk lipid’s melting point (61.56°C), while NLC20 exhibited two melting points at 54.80 and 59.10°C. These findings suggest that polysorbate 80 was a better dispersing agent for NLC than polysorbate 20. The physicochemistry properties of the NLCs are greatly influenced by the type of surfactant used. The small size and superior particle surface to volume ratio would increase loading efficiency and bioavailability of drugs, thus making NLC a promising drug delivery system.Key words: Nanostructured lipid carriers, colloidal delivery system,   polysorbate 80, polysorbate 20, highpressure homogenization,   physicochemical properties

Intelligent Cooperative Control Architecture: A Framework for Performance Improvement Using Safe Learning

Planning for multi-agent systems such as task assignment for teams of limited-fuel unmanned aerial vehicles (UAVs) is challenging due to uncertainties in the assumed models and the very large size of the planning space. Researchers have developed fast cooperative planners based on simple models (e.g., linear and deterministic dynamics), yet inaccuracies in assumed models will impact the resulting performance. Learning techniques are capable of adapting the model and providing better policies asymptotically compared to cooperative planners, yet they often violate the safety conditions of the system due to their exploratory nature. Moreover they frequently require an impractically large number of interactions to perform well. This paper introduces the intelligent Cooperative Control Architecture (iCCA) as a framework for combining cooperative planners and reinforcement learning techniques. iCCA improves the policy of the cooperative planner, while reduces the risk and sample complexity of the learner. Empirical results in gridworld and task assignment for fuel-limited UAV domains with problem sizes up to 9 billion state-action pairs verify the advantage of iCCA over pure learning and planning strategies

Residency patterns and migration dynamics of adult bull sharks (Carcharhinus leucas) on the east coast of southern Africa:

Bull sharks (Carcharhinus leucas) are globally distributed top predators that play an important ecological role within coastal marine communities. However, little is known about the spatial and temporal scales of their habitat use and associated ecological role. In this study, we employed passive acoustic telemetry to investigate the residency patterns and migration dynamics of 18 adult bull sharks (195–283 cm total length) tagged in southern Mozambique for a period of between 10 and 22 months. The majority of sharks (n = 16) exhibited temporally and spatially variable residency patterns interspersed with migration events. Ten individuals undertook coastal migrations that ranged between 433 and 709 km (mean  = 533 km) with eight of these sharks returning to the study site

Clinical and demographic predictors for vitamin D deficiency in multiethnic Asian patients with chronic kidney disease

10.1093/ckj/sfs074CKJ: Clinical Kidney Journal54303-308UNITED KINGDO

Development of erythropoietin receptor-targeted drug delivery system against breast cancer using tamoxifen-loaded nanostructured lipid carriers

Chaw Yee Beh,1 Chee Wun How,1,2 Jhi Biau Foo,2 Jia Ning Foong,3 Gayathri Thevi Selvarajah,3 Abdullah Rasedee1,3 1Laboratory of Vaccines and Immunotherapeutics, Institute of Bioscience, Universiti Putra Malaysia, Serdang, 2Faculty of Pharmacy, MAHSA University, Jenjarom, 3Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang, Malaysia Abstract: Tamoxifen (TAM) has been used in the treatment of breast cancers and is supplemented with erythropoietin (EPO) to alleviate the cancer-related anemia. The purported deleterious effects caused by the use of EPO with chemotherapeutic agents in the treatment of cancer-related anemia vary across studies and remain controversial. The use of nanoparticles as a drug delivery system has the potential to improve the specificity of anticancer drugs. In this study, we simultaneously incorporated two pharmacological active ingredients in one nanocarrier to develop EPO-conjugated TAM-loaded lipid nanoparticles (EPO-TAMNLC), a targeted delivery system, to enhance the cytotoxic activity while reducing the side effects of the ingredients. The effect of temperature in modulating the thermodynamic parameters associated with the binding of EPO and TAMNLC was assessed using isothermal titration calorimetry, while the unfolding of EPO structure was determined using fluorescence-quenching approach. The association efficiency of EPO and TAMNLC was 55.43%. Unlike binding of albumin to TAMNLC, the binding of EPO to TAMNLC occurred through endothermic and entropy-driven reaction. The EPO-TAMNLC formulation was stable because of the hydrophobic interaction and the high free energy, suggesting the spontaneity of the interactions between EPO and TAMNLC. The EPO-TAMNLC enhanced the in vitro cytotoxicity of TAM to MCF-7 cells. The EPO surface-functionalized TAMNLC could sequentially deliver EPO and TAM as well as improving site-specific delivery of these therapeutic compounds. Keywords: tamoxifen, thermodynamic interaction, albumi

Zerumbone-loaded nanostructured lipid carriers: preparation, characterization, and antileukemic effect

Heshu Sulaiman Rahman,1–3 Abdullah Rasedee,1,2 Chee Wun How,2 Ahmad Bustamam Abdul,2 Nazariah Allaudin Zeenathul,1,2 Hemn Hassan Othman,1 Mohamed Ibrahim Saeed,2 Swee Keong Yeap21Department of Microbiology and Pathology, Faculty of Veterinary Medicine, University Putra Malaysia, Serdang, Selangor, Malaysia; 2Institute of Bioscience, University Putra Malaysia, Serdang, Selangor, Malaysia; 3Department of Microbiology, Faculty of Veterinary Medicine, University of Sulaimanyah, Sulaimanyah City, Kurdistan Region, Northern IraqAbstract: Zerumbone, a natural dietary lipophilic compound with low water solubility (1.296 mg/L at 25°C) was used in this investigation. The zerumbone was loaded into nanostructured lipid carriers using a hot, high-pressure homogenization technique. The physicochemical properties of the zerumbone-loaded nanostructured lipid carriers (ZER-NLC) were determined. The ZER-NLC particles had an average size of 52.68 ± 0.1 nm and a polydispersity index of 0.29 ± 0.004 µm. Transmission electron microscopy showed that the particles were spherical in shape. The zeta potential of the ZER-NLC was −25.03 ± 1.24 mV, entrapment efficiency was 99.03%, and drug loading was 7.92%. In vitro drug release of zerumbone from ZER-NLC was 46.7%, and for a pure zerumbone dispersion was 90.5% over 48 hours, following a zero equation. Using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay in human T-cell acute lymphoblastic leukemia (Jurkat) cells, the half maximal inhibitory concentration (IC50) of ZER-NLC was 5.64 ± 0.38 µg/mL, and for free zerumbone was 5.39 ± 0.43 µg/mL after 72 hours of treatment. This study strongly suggests that ZER-NLC have potential as a sustained-release drug carrier system for the treatment of leukemia.Keywords: zerumbone, nanostructured lipid carrier, leukemi

Thymoquinone-loaded nanostructured lipid carriers: preparation, gastroprotection, in vitro toxicity, and pharmacokinetic properties after extravascular administration

Siddig Ibrahim Abdelwahab,1 Bassem Yousef Sheikh,2 Manal Mohamed Elhassan Taha,1 Chee Wun How,3 Rasedee Abdullah,3 Umar Yagoub,1 Rashad El-Sunousi,1 Eltayeb EM Eid31Medical Research Centre, Jazan University, Jazan, Saudi Arabia; 2Department of Surgery, College of Medicine, Taibah University, Medina, Saudi Arabia; 3Laboratory of Vaccines and Immunotherapeutics, Institute of Bioscience, University Putra Malaysia, Serdang, MalaysiaBackground: Nanostructured lipid carriers (NLCs), composed of solid and liquid lipids, and surfactants are potentially good colloidal drug carriers. Thymoquinone is the main bioactive compound of Nigella sativa. In this study, the preparation, gastroprotective effects, and pharmacokinetic (PK) properties of thymoquinone (TQ)-loaded NLCs (TQNLCs) were evaluated.Method: TQNLCs were prepared using hydrogenated palm oil (Softisan® 154), olive oil, and phosphatidylcholine for the lipid phase and sorbitol, polysorbate 80, thimerosal, and double distilled water for the liquid lipid material. A morphological assessment of TQNLCs was performed using various methods. Analysis of the ulcer index, hydrogen concentration, mucus content, and biochemical and histochemical studies confirmed that the loading of TQ into the NLCs significantly improved the gastroprotective activity of this natural compound against the formation of ethanol-induced ulcers. The safety of TQNLC was tested on WRL68 liver normal cells with cisplatin as a positive control.Results: The average diameter of the TQNLCs was 75 ± 2.4 nm. The particles had negative zeta potential values of −31 ± 0.1 mV and a single melting peak of 55.85°C. Immunohistochemical methods revealed that TQNLCs inhibited the formation of ethanol-induced ulcers through the modulation of heat shock protein-70 (Hsp70). Acute hepatotoxic effects of the TQNLCs were not observed in rats or normal human liver cells (WRL-68). After validation, PK studies in rabbits showed that the PK properties of TQ were improved and indicated that the drug behaves linearly. The Tmax, Cmax, and elimination half-life of TQ were found to be 3.96 ± 0.19 hours, 4811.33 ± 55.52 ng/mL, and 4.4933 ± 0.015 hours, respectively, indicating that TQ is suitable for extravascular administration.Conclusion: NLCs could be a promising vehicle for the oral delivery of TQ and improve its gastroprotective properties.Keywords: lipid based nanoparticles, black seed oil, gastric ulce

Zerumbone-loaded nanostructured lipid carrier induces G2/M cell cycle arrest and apoptosis via mitochondrial pathway in a human lymphoblastic leukemia cell line

Heshu Sulaiman Rahman,1–3 Abdullah Rasedee,1,2 Ahmad Bustamam Abdul,2,4 Nazariah Allaudin Zeenathul,1,2 Hemn Hassan Othman,1,3 Swee Keong Yeap,2 Chee Wun How,2 Wan Abd Ghani Wan Nor Hafiza4,51Faculty of Veterinary Medicine, 2Institute of Bioscience, Universiti Putra Malaysia, Selangor, Malaysia; 3Faculty of Veterinary Medicine, University of Sulaimanyah, Sulaimanyah City, Kurdistan Region, Northern Iraq; 4Faculty of Medicine and Health Science, Universiti Putra Malaysia, Selangor, Malaysia; 5College of Medical Laboratory Technology, Institute for Medical Research, Kuala Lumpur, MalaysiaAbstract: This investigation evaluated the antileukemia properties of a zerumbone (ZER)-loaded nanostructured lipid carrier (NLC) prepared by hot high-pressure homogenization techniques in an acute human lymphoblastic leukemia (Jurkat) cell line in vitro. The apoptogenic effect of the ZER-NLC on Jurkat cells was determined by fluorescent and electron microscopy, Annexin V-fluorescein isothiocyanate, Tdt-mediated dUTP nick-end labeling assay, cell cycle analysis, and caspase activity. An MTT (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide) assay showed that ZER-NLC did not have adverse effects on normal human peripheral blood mononuclear cells. ZER-NLC arrested the Jurkat cells at G2/M phase with inactivation of cyclin B1 protein. The study also showed that the antiproliferative effect of ZER-NLC on Jurkat cells is through the intrinsic apoptotic pathway via activation of caspase-3 and caspase-9, release of cytochrome c from the mitochondria into the cytosol, and subsequent cleavage of poly (adenosine diphosphate-ribose) polymerase (PARP). These findings show that the ZER-NLC is a potentially useful treatment for acute lymphoblastic leukemia in humans.Keywords: zerumbone-loaded nanostructured lipid carrier, cell cycle arrest, apoptosis, mitochondrial pathwa