Effect of Deep Eutectic System (DES) on Oral Bioavailability of Celecoxib: In Silico, In Vitro, and In Vivo Study.

Different deep eutectic systems (DES) of choline chloride (CC)-urea (UA) (1:2), CC-glycerol (GLY) (1:2), CC-malonic acid (MA) (1:1), and CC-ascorbic acid (AA) (2:1) were generated and characterized by polarized light microscope (PLM) and Fourier transform infrared spectroscope (FTIR). The equilibrium solubility of celecoxib (CLX) in DES was compared to that in deionized water. The CC-MA (1:1) system provided ~10,000 times improvement in the solubility of CLX (13,114.75 µg/g) and was used for the generation of the CLX-DES system. The latter was characterized by PLM and FTIR to study the microstructure and intermolecular interaction between the CLX and CC-MA (1:1) DES. FTIR demonstrated the retention of the chemical structure of CLX. In vitro drug release studies in FaSSIF initially demonstrated high supersaturation, which decreased by ~2 fold after 2 h. Density functional theory (DFT)-based calculations provided a molecular-level understanding of enhanced solubility. Gibbs free energy calculations established the role of the strongest binding of CLX with CC and MA. A phase solubility study highlighted the role of hydrotropy-induced solubilization of the CLX-DES system. Animal pharmacokinetic studies established 2.76 times improvement in Cmax, 1.52 times reduction in tmax, and 1.81 times improvement in AUC0-∞. The overall results demonstrated the potential of developing a DES-based supersaturating drug-delivery system for pharmaceutical loading of drugs having solubility and dissolution rate-limited oral bioavailability.

Deep eutectic systems: An overview of fundamental aspects, current understanding and drug delivery applications.

The deep eutectic system (DES) is a relatively new concept in the field of drug delivery science. DES is a class of eutectic mixtures comprised of two or more components, with a eutectic point far below than the melting temperature of the pure components. The strong hydrogen bonding interactions between DES constituents are responsible for significant lowering of melting point in DES. A significant number of molecules cannot reach from drug discovery phase to drug development phase because of poor biopharmaceutical attributes, such as solubility and permeability. DES can be a novel alternative to overcome these issues. In last few years DESs have been widely used in different pharmaceutical and chemical processes. However, comprehensive information regarding their drug delivery potential is not available. This review deals with fundamental aspects such as types, preparation, thermodynamics, toxicity, biodegradability and their applications in the field of drug delivery. Current challenges, future prospects and translational aspects of DES as drug delivery system have also been discussed.

Robotic excision of a pre-coccygeal nerve root tumor.

Pre-coccygeal ganglioneuroma is a rare clinical entity that presents incidentally or with non-specific symptoms. We present a case of a 25 year old housewife who was incidentally diagnosed with pre-coccygeal ganglioneuroma while getting investigated for primary infertility. The patient had no specific complaints except for irregular menstruation which had started 8 months back. Magnetic resonance imaging (MRI) was suggestive of a presacral and pre-coccygeal lesion. Resection of the tumor was done through the anterior approach using the da Vinci Si robotic system. Two robotic arms and one assistant port were used to completely excise the tumor. Robotic excision of such a tumor mass located at a relatively inaccessible area allows enhanced precision and 3-dimentional (3D) view avoiding damage to important surrounding structures.

Primary neuroendocrine tumor of the left hepatic duct: a case report with review of the literature.

Primary Biliary Tract Neuroendocrine tumors (NET) are extremely rare tumors with only 77 cases been reported in the literature till now. We describe a case of a left hepatic duct NET and review the literature for this rare malignancy. To the best of our knowledge the present case is the first reported case of a left hepatic duct NET in the literature. In spite of availability of advanced diagnostic tools like Computerized Tomography (CT) Scan and Endoscopic Retrograde Cholangio Pancreaticography (ERCP) a definitive diagnosis of these tumors is possible only after an accurate histopathologic diagnosis of operative specimens with immunohistochemistry and electron microscopy. Though surgical excision remains the gold standard treatment for such tumors, patients with unresectable tumors have good survival with newer biologic agents like Octreotride.

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The term "robot" was coined by the Czech playright Karel Capek in 1921 in his play Rossom's Universal Robots. The word "robot" is from the check word robota which means forced labor. The era of robots in surgery commenced in 1994 when the first AESOP (voice controlled camera holder) prototype robot was used clinically in 1993 and then marketed as the first surgical robot ever in 1994 by the US FDA. Since then many robot prototypes like the Endoassist (Armstrong Healthcare Ltd., High Wycombe, Buck, UK), FIPS endoarm (Karlsruhe Research Center, Karlsruhe, Germany) have been developed to add to the functions of the robot and try and increase its utility. Integrated Surgical Systems (now Intuitive Surgery, Inc.) redesigned the SRI Green Telepresence Surgery system and created the daVinci Surgical System((R)) classified as a master-slave surgical system. It uses true 3-D visualization and EndoWrist((R)). It was approved by FDA in July 2000 for general laparoscopic surgery, in November 2002 for mitral valve repair surgery. The da Vinci robot is currently being used in various fields such as urology, general surgery, gynecology, cardio-thoracic, pediatric and ENT surgery. It provides several advantages to conventional laparoscopy such as 3D vision, motion scaling, intuitive movements, visual immersion and tremor filtration. The advent of robotics has increased the use of minimally invasive surgery among laparoscopically naïve surgeons and expanded the repertoire of experienced surgeons to include more advanced and complex reconstructions.