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Drug Delivery and Translational Research

Jens Wesholowski, Sebastian Prill, Andreas Berghaus, Markus Thommes
Hot-melt extrusion on co-rotating twin screw extruders is a focused technology for the production of pharmaceuticals in the context of Quality by Design. Since it is a continuous process, the potential for minimizing product quality fluctuation is enhanced. A typical application of hot-melt extrusion is the production of solid dispersions, where an active pharmaceutical ingredient (API) is distributed within a polymer matrix carrier. For this dosage form, the product quality is related amongst others to the drug content...
January 11, 2018: Drug Delivery and Translational Research
Martin Le Nedelec, Paul Glue, Helen Winter, Chelsea Goulton, Lucy Broughton, Natalie Medlicott
Peripheral BDNF changes after ketamine administration have been proposed as a biomarker for brain BDNF changes. However, published data are conflicting and come from studies in paired animal groups. This study determined the time course of plasma BDNF concentrations following the administration of a single 10 mg/kg dose of ketamine by different routes of administration in rats. Brain BDNF concentrations in prefrontal cortex, hippocampus and cortex were measured in the same animals. Ketamine administration resulted in a rapid and robust increase in plasma BDNF concentrations that were sustained for 240 min...
January 10, 2018: Drug Delivery and Translational Research
Armin Mooranian, Rebecca Negrulj, Ryu Takechi, John Mamo, Hesham Al-Sallami, Hani Al-Salami
Probucol (PB) is an hypolipidaemic drug with potential antidiabetic effects. We showed recently using in vitro studies that when PB was incorporated with stabilising lipophilic bile acids and microencapsulated using the polymer sodium alginate, the microcapsules showed good stability but poor and irregular PB release. This suggests that PB microcapsules may exhibit better release profile and hence better absorption, if more hydrophilic bile acids were used, such as ursodeoxycholic acid (UDCA). Accordingly, this study aimed to produce PB-UDCA microcapsules and examine PB absorption and antidiabetic effects in our mouse-model of insulin-resistance and diabetes (fed high-fat diet; HFD)...
January 8, 2018: Drug Delivery and Translational Research
Rasha R Radwan, Heba A Mohamed, H E Ali, Ghada A Mahmoud
In the present study, L-arginine/acrylic acid (Arg/AAc) batch hydrogel was successfully prepared by gamma irradiation for transdermal delivery of propranolol HCl in hypertensive rats. The resulted system has been characterized by FTIR to confirm the hydrogel formation. The swelling behavior of the prepared hydrogels was investigated as a function of time and pH. The kinetics of swelling has been investigated. In vivo pharmacokinetics evaluation, skin irritation test, and histopathological studies were investigated...
January 8, 2018: Drug Delivery and Translational Research
Najwa Mohamad, Evelyn Yun Xi Loh, Mh Busra Fauzi, Min Hwei Ng, Mohd Cairul Iqbal Mohd Amin
The healing of wounds, including those from burns, currently exerts a burden on healthcare systems worldwide. Hydrogels are widely used as wound dressings and in the field of tissue engineering. The popularity of bacterial cellulose-based hydrogels has increased owing to their biocompatibility. Previous study demonstrated that bacterial cellulose/acrylic acid (BC/AA) hydrogel increased the healing rate of burn wound. This in vivo study using athymic mice has extended the use of BC/AA hydrogel by the addition of human epidermal keratinocytes and human dermal fibroblasts...
January 4, 2018: Drug Delivery and Translational Research
Sébastien Goutal, Oliver Langer, Sylvain Auvity, Karine Andrieux, Christine Coulon, Fabien Caillé, Philippe Gervais, Salvatore Cisternino, Xavier Declèves, Nicolas Tournier
Elacridar (GF120918) is a highly potent inhibitor of both P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2), the main efflux transporters expressed at the blood-brain barrier (BBB). Elacridar shows very low aqueous solubility, which complicates its formulation for i.v. administration. An intravenous infusion protocol would be preferred to achieve high and controlled plasma concentrations of elacridar in large animals, including nonhuman primates. Formulation of elacridar for i.v. infusion was achieved using a co-solvent strategy, resulting in an aqueous dispersion with a final concentration of 5 g L-1 elacridar with tetrahydrofuran (5% w/v) in aqueous D-glucose solution (2...
January 2, 2018: Drug Delivery and Translational Research
Maria Natalia Calienni, Carlos Facundo Temprana, Maria Jimena Prieto, Donatella Paolino, Massimo Fresta, Ayse Begum Tekinay, Silvia Del Valle Alonso, Jorge Montanari
With the aim of improving the topical delivery of the antineoplastic drug 5-fluorouracil (5FU), it was loaded into ultradeformable liposomes composed of soy phosphatidylcholine and sodium cholate (UDL-5FU). The liposome populations had a mean size of 70 nm without significant changes in 56 days, and the ultradeformable formulations were up to 324-fold more elastic than conventional liposomes. The interaction between 5FU and the liposomal membrane was studied by three methods, and also release profile was obtained...
December 30, 2017: Drug Delivery and Translational Research
Tamara N Tarbox, Alan B Watts, Zhengrong Cui, Robert O Williams
Recently, results have been published for the first successful phase I human clinical trial investigating the use of dissolving polymeric microneedles… Even so, further clinical development represents an important hurdle that remains in the translation of microneedle technology to approved products. Specifically, the potential for accumulation of polymer within the skin upon repeated application of dissolving and coated microneedles, combined with a lack of safety data in humans, predicates a need for further clinical investigation...
December 29, 2017: Drug Delivery and Translational Research
Shubhmita Bhatnagar, Amala Saju, Krishna Deepthi Cheerla, Sudeep Kumar Gade, Prashant Garg, Venkata Vamsi Krishna Venuganti
Penetration of antibiotics into and through the cornea is a major limiting factor in the treatment of ocular infections. Several strategies are in vogue to overcome this limitation such as use of fortified drops, gels, and subconjunctival injections. Here, we present the fabrication of rapidly dissolving polymeric microneedle array to effectively deliver besifloxacin through the cornea. Microneedles were prepared using polyvinyl alcohol and polyvinyl pyrrolidone by the micromolding technique. The model fluoroquinolone antibiotic, besifloxacin, was loaded in 36 microneedles arranged in a 6 × 6 array format within a 1 cm2 area...
December 29, 2017: Drug Delivery and Translational Research
Miguel O Jara, Johanna Catalan-Figueroa, Mariana Landin, Javier O Morales
Nanoprecipitation is a simple and fast method to produce polymeric nanoparticles (Np); however, most applications require filtration or another separation technique to isolate the nanosuspension from aggregates or polydisperse particle production. In order to avoid variability introduced by these additional steps, we report here a systematic study of the process to yield monomodal and uniform Np production with the nanoprecipitation method. To further identify key variables and their interactions, we used artificial neural networks (ANN) to investigate the multiple variables which influence the process...
December 29, 2017: Drug Delivery and Translational Research
Raisa Yu Kiseleva, Patrick M Glassman, Colin F Greineder, Elizabeth D Hood, Vladimir V Shuvaev, Vladimir R Muzykantov
Vascular endothelial cells represent an important therapeutic target in many pathologies, including inflammation, oxidative stress, and thrombosis; however, delivery of drugs to this site is often limited by the lack of specific affinity of therapeutics for these cells. Selective delivery of both small molecule drugs and therapeutic proteins to the endothelium has been achieved through the use of targeting ligands, such as monoclonal antibodies, directed against endothelial cell surface markers, particularly cell adhesion molecules (CAMs)...
December 28, 2017: Drug Delivery and Translational Research
Heba A Mohamed, Rasha R Radwan, Amany I Raafat, Amr El-Hag Ali
In an effort to increase the oral bioavailability of Amphotericin B (AmB), a pH-sensitive drug carrier composed of Tragacanth (Trag) and acrylic acid (AAc) was prepared using γ-irradiation. The swelling behavior of (Trag/AAc) hydrogels was characterized as a function of pH and ionic strength of the swelling medium. The obtained swelling indices revealed the ability of the prepared hydrogel to protect a loaded drug in stomach-simulated medium (Fickian behavior) and to release such drug in intestinal-simulated medium (non-Fickian behavior)...
December 27, 2017: Drug Delivery and Translational Research
Hajar Moghadas, Mohammad Said Saidi, Navid Kashaninejad, Nam-Trung Nguyen
Micro and nanotechnology can potentially revolutionize drug delivery systems. Novel microfluidic systems have been employed for the cell culture applications and drug delivery by micro and nanocarriers. Cells in the microchannels are under static and dynamic flow perfusion of culture media that provides nutrition and removes waste from the cells. This exerts hydrostatic and hydrodynamic forces on the cells. These forces can considerably affect the functions of the living cells. In this paper, we simulated the flow of air, culture medium, and the particle transport and deposition in the microchannels under different angles of connection inlet...
December 21, 2017: Drug Delivery and Translational Research
Carlos Molina, Waseem Kaialy, Qiao Chen, Daniel Commandeur, Ali Nokhodchi
Spray-drying allows to modify the physicochemical/mechanical properties of particles along with their morphology. In the present study, L-leucine with varying concentrations (0.1, 0.5, 1, 5, and 10% w/v) were incorporated into lactose monohydrate solution for spray-drying to enhance the aerosolization performance of dry powder inhalers containing spray-dried lactose-leucine and salbutamol sulfate. The prepared spray-dried lactose-leucine carriers were analyzed using laser diffraction (particle size), differential scanning calorimetry (thermal behavior), scanning electron microscopy (morphology), powder X-ray diffraction (crystallinity), Fourier transform infrared spectroscopy (interaction at molecular level), and in vitro aerosolization performance (deposition)...
December 19, 2017: Drug Delivery and Translational Research
Hye-Gyeong Kim, Deborah L Gater, Yeu-Chun Kim
Although vitamin D3 (VD3), which is the main form of vitamin D, can be produced in human skin under the sunlight, vitamin D deficiency emerged as a major public health problem worldwide. Mainly, oral supplements or vitamin D-fortified foods are distributed to help supplementation of vitamin D. However, those oral methods are limitedly supplied in the Middle East countries, and oral absorption has low efficiency due to many barriers and various changes of conditions along the route. Then, it is recommended to take them every day in order to maintain the adequate serum level of vitamin D...
December 16, 2017: Drug Delivery and Translational Research
Moe Wehbe, Armaan K Malhotra, Malathi Anantha, Cody Lo, Wieslawa H Dragowska, Nancy Dos Santos, Marcel B Bally
Clioquinol (CQ) is an FDA-approved topical antifungal agent known to kill cancer cells. This facilitated the initiation of clinical trials in patients with refractory hematologic malignancies. These repurposing efforts were not successful; this was likely due to low intracellular levels of the drug owing to poor absorption and rapid metabolism upon oral administration. CQ forms a sparingly soluble copper complex (Cu(CQ)2) that exhibits enhanced anticancer activity in some cell lines. We have utilized a novel method to synthesize Cu(CQ)2 inside liposomes, an approach that maintains the complex suspended in solution and in a format suitable for intravenous administration...
December 16, 2017: Drug Delivery and Translational Research
K Cao, Y Liu, A A Olkhov, V Siracusa, A L Iordanskii
Fibers of poly(L-lactic acid) (PLLA)/polyhydroxybutyrate (PHB) with different concentrations of the drug dipyridamole (DPD) were prepared using solvent-free melt electrospinning to obtain a polymeric drug delivery system. The electrospun fibers were morphologically, structurally, thermally, and dynamically characterized. Crazes that resemble lotus root crevices were interestingly observed in the 7:3 PLLA/PHB fibers with 1% DPD. The crystallinity of PLLA slightly decreased as PHB was incorporated, and the addition of DPD significantly reduced the melting temperature of the composite...
December 12, 2017: Drug Delivery and Translational Research
Xin Feng, Feng Zhang
Most of published reviews of twin-screw extrusion focused on its application for enhancing the bioavailability of amorphous solid dispersions while few of them focused on its use for manufacturing sustained-release oral dosage forms and medical implants, despite the considerable interest and success this process has garnered both in academia and in the pharmaceutical industry. Compared to conventional batch processing, twin-screw extrusion offers the advantages of continuous processing and the ability to prepare oral dosage forms and medical implants that have unique physicochemical and drug release attributes...
December 12, 2017: Drug Delivery and Translational Research
Amit Kumar Chaudhary, Rajan Sharma Bhattarai, Ram I Mahato
Precision medicine is promising for treating human diseases, as it focuses on tailoring drugs to a patient's genes, environment, and lifestyle. The need for personalized medicines has opened the doors for turning nucleic acids into therapeutics. Although gene therapy has the potential to treat and cure genetic and acquired diseases, it needs to overcome certain obstacles before creating the overall prescription drugs. Recent advancement in the life science has helped to understand the effective manipulation and delivery of genome-engineering tools better...
December 5, 2017: Drug Delivery and Translational Research
Mahendra Singh, Jovita Kanoujia, Poonam Parashar, Malti Arya, Chandra B Tripathi, V R Sinha, Shailendra K Saraf, Shubhini A Saraf
The oral bioavailability of felodipine, a dihydropyridine calcium channel antagonist, is about 15%. This may be due to poor water solubility, and a lower intestinal permeability than a BCS class I drug, and hepatic first-pass metabolism of the drug. Many drugs are unpopular due to solubility issues. The goal of this study was to develop and optimize a felodipine-containing microemulsion to improve the intestinal permeability and bioavailability of the drug. The felodipine microemulsions were developed with the selected components, i...
December 4, 2017: Drug Delivery and Translational Research
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