Drug Delivery Studies Research Articles

Carboxymethyl cellulose-based nanocomposite hydrogel grafted with vinylic comonomers: synthesis, swelling behavior and drug delivery investigation

Carboxymethyl cellulose-based nanocomposite hydrogel was produced through in-situ free-radical copolymerization for use in drug delivery study. The pure hydrogel and their nanocomposite structure were systematically identified by XRD, FTIR, SEM, TEM, TGA-DTA techniques. The swelling and deswelling properties, which are affected by several factors such as pH (due to the carboxylate groups) and time were studied. The swelling rate improved with the SiO2 nanoparticles. Also, the swelling ratio in NaCl, CaCl2 and AlCl3 salt solutions were investigated and it was found that swelling capacity was 41 and 37 g/g for pure and nanocomposite hydrogel in NaCl solution, respectively. Diclofenac sodium was utilized as a model of drug and the drug release after loaded in the nanocomposite hydrogels was studied. The results revealed essential performances on the subject of physiological-simulated pH media. The maximum cumulative drug releases attained were 90.13% and 79.26% at pH values of 7.4 for nanocomposite and pure hydrogel, respectively. The applicability of drug release kinetic models such as Ritger–Peppas, zero and first-order kinetic models was proved. According to the information obtained from Ritger–Peppas model, the drug release mechanism follows non-Fickian diffusion and indicates an anomalous transport.

Isolation of Platelet-Derived Exosomes from Human Platelet-Rich Plasma: Biochemical and Morphological Characterization.

Platelet-Rich Plasma (PRP) is enriched in molecular messengers with restorative effects on altered tissue environments. Upon activation, platelets release a plethora of growth factors and cytokines, either in free form or encapsulated in exosomes, which have been proven to promote tissue repair and regeneration. Translational research on the potential of exosomes as a safe nanosystem for therapeutic cargo delivery requires standardizing exosome isolation methods along with their molecular and morphological characterization. With this aim, we isolated and characterized the exosomes released by human PRP platelets. Western blot analysis revealed that CaCl2-activated platelets (PLT-Exos-Ca2+) released more exosomes than non-activated ones (PLT-Exos). Moreover, PLT-Exos-Ca2+ exhibited a molecular signature that meets the most up-to-date biochemical criteria for platelet-derived exosomes and possessed morphological features typical of exosomes as assessed by transmission electron microscopy. Array analysis of 105 analytes including growth factors and cytokines showed that PLT-Exos-Ca2+ exhibited lower levels of most analytes compared to PLT-Exos, but relatively higher levels of those consistently validated as components of the protein cargo of platelet exosomes. In summary, the present study provides new insights into the molecular composition of human platelet-derived exosomes and validates a method for isolating highly pure platelet exosomes as a basis for future preclinical studies in regenerative medicine and drug delivery.

Detection of Label-Free Drugs within Brain Tissue Using Orbitrap Secondary Ion Mass Spectrometry as a Complement to Neuro-Oncological Drug Delivery.

Historically, pre-clinical neuro-oncological drug delivery studies have exhaustively relied upon overall animal survival as an exclusive measure of efficacy. However, with no adopted methodology to both image and quantitate brain parenchyma penetration of label-free drugs, an absence of efficacy typically hampers clinical translational potential, rather than encourage re-formulation of drug compounds using nanocarriers to achieve greater tissue penetration. OrbiSIMS, a next-generation analytical instrument for label-free imaging, combines the high resolving power of an OrbiTrapTM mass spectrometer with the relatively high spatial resolution of secondary ion mass spectrometry. Here, we develop an ex vivo pipeline using OrbiSIMS to accurately detect brain penetration of drug compounds. Secondary ion spectra were acquired for a panel of drugs (etoposide, olaparib, gemcitabine, vorinostat and dasatinib) under preclinical consideration for the treatment of isocitrate dehydrogenase-1 wild-type glioblastoma. Each drug demonstrated diagnostic secondary ions (all present molecular ions [M-H]− which could be discriminated from brain analytes when spiked at >20 µg/mg tissue. Olaparib/dasatinib and olaparib/etoposide dual combinations are shown as exemplars for the capability of OrbiSIMS to discriminate distinct drug ions simultaneously. Furthermore, we demonstrate the imaging capability of OrbiSIMS to simultaneously illustrate label-free drug location and brain chemistry. Our work encourages the neuro-oncology community to consider mass spectrometry imaging modalities to complement in vivo efficacy studies, as an analytical tool to assess brain distribution of systemically administered drugs, or localised brain penetration of drugs released from micro- or nano-scale biomaterials.

Three-dimensional simulation of red blood cell particle sedimentation

The red blood cell particle is important in the research studies of blood flow and drug delivery. The biconcave shape makes the motions of the red blood cell particle in fluids more complex than sphere or ellipsoid. Sedimentation behaviors of a red blood cell particle in long circular tubes are investigated by using the lattice Boltzmann method with the Galilean-invariant momentum exchange method. Different blockage ratios and the particle to fluid density ratios are considered. One periodic and two steady sedimentation modes are discovered. When the blockage ratio rises, the motion mode of particles changed from horizontal mode to inclined mode. With the increase of the particle to fluid density ratio, the sedimentation mode changed from the inclined mode to the horizontal mode, and the time of the particles reaching the stable state is obviously distinct in different sedimentation modes. Surprisingly, the oscillatory mode is observed in the larger blockage ratio and lower density ratio of particle to fluid. These works may be able to make active promotions to the research studies of blood circulation of humans.

Preparation and characterization of magnetic nanohydrogel based on chitosan for 5-fluorouracil drug delivery and kinetic study

Chemotherapy is currently used for most cancer treatments, but one of the significant problems of this treatment is that it affects the healthy tissues of the body. Therefore, designing new systems for the intelligent and controlled release of these drugs in cancer tissues is one of the major challenges in the world. Hence, today, huge costs are spent designing appropriate new drug delivery systems (DDS) with controlled drug release. In this study, chitosan-polyacrylic acid encapsulated Fe3O4 magnetic nanogelic core-shell (Fe3O4@CS-PAA) was synthesized in the presence of glutaraldehyde used for loaded anticancer 5-fluorouracil (5-FU) drug. Also, the prepared Fe3O4@CS-PAA was characterized by using FT-IR, SEM, XRD, and VSM analysis. Then, drug delivery tests were carried out in the in-vitro conditions that are the simulated physiological environment and tumor tissue conditions. The drug release tests indicated that the Fe3O4@CS-PAA upgraded the rate of 5-FU release from nanogelic core-shell under tumor tissue conditions (pH 4.5) than physiological environments (pH 7.4). In addition, various models were used to investigate the drug release mechanism. Results of modeling studies of drug release showed the mechanism of 5-FU release from Fe3O4@CS-PAA controlled by Fickian diffusion.

Controlled release of paroxetine from chitosan/montmorillonite composite films

Controlled drug delivery studies popular in pharmaceutical area; polymeric composites prepared with clay has a great potential importance in drug release studies. The aim of the study is to produce biocoposite material suitable for controlled release of Paroxetine Hydrochloride.In this study, chitosan/clay/paroxetine (CS/MMT/PHH and CS/NaMMT/PHH) composite films were prepared to investigate drug release properties of paroxetine (PHH). Films containing various amounts of clay (MMT/NaMMT) (0, 0.1, 0.2, 0.4 g) and glycerol (0.25, 0.50) were prepared by solvent casting method. The structural properties of drug-containing and non-drug containing films were characterized by FT-IR and SEM analysis. The release studies of PHH were done in vitro and pH 7.4 and at 37 °C temperature. The highest percent of drug release was observed with CS/PHH film after 170 h (69%). It was observed that the drug release profiles of chitosan films containing clay (MMT or NaMMT) were better than films without clay. In order to investigate the drug release mechanism, Korsmeyer-Peppas, Higuchi, Zero and First order kinetic models were used.It was determined that release kinetics of the most of films fit the Korsmeyer-Peppas model, and according to this model, drug release occurs through two mechanisms, swelling-controlled and diffusion-controlled. It has been observed that all films containing clay have long-term drug release. Increasing in clay ratio in the composite, caused decrease in drug release rate. PHH loaded CS/MMT/PHH and CS/NaMMT/PHH films showed steady and prolonged drug delivery. Results indicated that prepared CS/MMT/PHH and CS/NaMMT/PHH films has a potential to act as suitable carrier for drugs.

Theoretical and Experimental Study of the Water-Based Drug Delivery under the Nail Plate by Er-Laser Radiation

Double-stage active laser drug delivery (DSLADD) of an aqueous solution of methylene blue using Er:YLF laser radiation experimentally was investigated. Model for describe of the delivery of local drugs under a microporated nail plate taking into account the peculiarities of laser radiation exposure, capillary effects in microholes and diffusion in the nail plate was developed. The phenomenon of spreading of the drug consisting in the fact that after laser action drug is distributed in the nail bed not only in the area of the nail bed located directly under the microhole, but also along the border of the nail plate and the nail bed around the microhole was observed for the first time. Calculations performed within the framework of the developed model showed that, taking into account spreading phenomenon, the density of filling the nail area with microholes can be significantly reduced, which can proportionally increase the productivity of laser delivery in general.

Advancing fluorescence microscopy and spectroscopy for the benefit of cell science and drug delivery

Here we report on two recent advances we made applying advanced fluorescence microscopy and spectroscopy to further the study of cell biology and drug delivery. At first, we detail a new instrumental set-up combining atomic force microscopy in liquid and super-resolution fluorescence microscopy in novel configuration such that long-term simultaneous and co-localized observation with both techniques becomes feasible. We believe this will contribute to the study of fast membrane activated cell-signalling processes in the years to come. Furthermore, we report on a novel application of fluorescence cross-correlation spectroscopy (FCCS) for the characterization of lipid-nucleic acid complexes. We could determine the number of nucleic acid particles incorporated in each liposome, a parameter not readily accessible on ensemble basis with other methods. This parameter is crucial for co-delivery applications, and we believe FCCS can play an important role in the future development of new drug delivery systems.

Two-way coupling and Kolmogorov scales on inhaler spray plume evolutions from Ventolin, ProAir, and Qvar.

Previous numerical studies of pulmonary drug delivery using metered-dose inhalers (MDIs) often neglected the momentum transfer from droplets to fluid. However, Kolmogorov length scales in MDI flows can be comparable to the droplet sizes in the orifice vicinity, and their interactions can modify the spray behaviors. This study aimed to evaluate the two-way coupling effects on spray plume evolutions compared to one-way coupling. The influences from the mass loading, droplet size, and inhaler type were also examined. Large-eddy simulation and Lagrangian approach were used to simulate the flow and droplet motions. Two-way coupled predictions appeared to provide significantly improved predictions of the aerosol behaviors close to the Ventolin orifice than one-way coupling. Increasing the applied MDI dose mass altered both the fluid and aerosol dynamics, notably bending the spray plume downward when applying a dose ten times larger. The droplet size played a key role in spray dynamics, with the plume being suppressed for 2-µm aerosols and enhanced for 20-µm aerosols. The Kolmogorov length scale ratio dp/η correlated well with the observed difference in spray plumes, with suppressed plumes when dp/η < 0.1 and enhanced plumes when dp/η > 0.1. For the three inhalers considered (Ventolin, ProAir, and Qvar), significant differences were predicted using two-way and one-way coupling despite the level and manifestation of these differences varied. Two-way coupling effects were significant for MDI sprays and should be considered in future numerical studies.

Stimuli-responsive spin crossover nanoparticles for drug delivery and DNA-binding studies

Aminated silica hybrid, spin-crossover (SCO) nanoparticles (AmNPs) coupled with (S)-naproxen (NAP) were proposed for potential drug nanocarriers through drug release experiments at various pH values. DNA- and albumin-binding studies were also carried out using diverse techniques in order to investigate the interaction of the nanoparticles with calf-thymus DNA and serum albumins and to determine the corresponding binding constants.

Doxorubicin delivery performance of superparamagnetic carbon multi-core shell nanoparticles: pH dependence, stability and kinetic insight

In the past decade, magnetic nanoparticles (MNPs) have been among the most attractive nanomaterials used in different fields, such as environmental and biomedical applications. The possibility of designing nanoparticles with different functionalities allows for advancing the biomedical applications of these materials. Additionally, the magnetic characteristics of the nanoparticles enable the use of magnetic fields to drive the nanoparticles to the desired sites of delivery. In this context, the development of new MNPs in new approaches for drug delivery systems (DDSs) for cancer treatment has increased. However, the synthesis of nanoparticles with high colloidal stability triggered drug delivery, and good biocompatibility remains a challenge. Herein, multi-core shell MNPs functionalized with Pluronic ® F-127 were prepared and thoroughly characterized as drug carriers for doxorubicin delivery. The functionalized nanoparticles have an average size of 17.71 ± 4.2 nm, high water colloidal stability, and superparamagnetic behavior. In addition, the nanoparticles were able to load 936 μg of DOX per mg of functionalized nanomaterial. Drug release studies at different pH values evidenced a pH-triggered DOX release effect. An increase of 62% in cumulative drug release was observed at pH simulating tumor endosome/lysosome microenvironments (pH 4.5) compared to physiological conditions (pH 7.4). In addition, an innovative dynamic drug delivery study was performed as a function of pH. The results from this test confirmed the pH-induced doxorubicin release capability of carbon multi-core shell MNPs. The validity of traditional kinetic models to fit dynamic pH-dependent drug release was also studied for predictive purposes.

Measurement of Residual Dipolar Couplings Using Magnetically Aligned and Flipped Nanodiscs.

Recent developments in lipid nanodisc technology have successfully overcome the major challenges in the structural and functional studies of membrane proteins and drug delivery. Among the different types of nanodiscs, the use of synthetic amphiphilic polymers created new directions including the applications of solution and solid-state NMR spectroscopy. The ability to magnetically align large-size (>20 nm diameter) polymer nanodiscs and flip them using paramagnetic lanthanide ions has enabled high-resolution studies on membrane proteins using solid-state NMR techniques. The use of polymer-based macro-nanodiscs (>20 nm diameter) as an alignment medium to measure residual dipolar couplings (RDCs) and residual quadrupole couplings by NMR experiments has also been demonstrated. In this study, we demonstrate the use of magnetically aligned and 90°-flipped polymer nanodiscs as alignment media for structural studies on proteins by solution NMR spectroscopy. These macro-nanodiscs, composed of negatively charged SMA-EA polymers and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) lipids, were used to measure residual 1H-15N dipolar couplings (RDCs) from the water-soluble ∼21 kDa uniformly 15N-labeled flavin mononucleotide binding domain (FBD) of cytochrome-P450 reductase. The experimentally measured 1H-15N RDC values are compared with the values calculated from the crystal structures of cytochrome-P450 reductase that lacks the transmembrane domain. The N-H RDCs measured using aligned and 90°-flipped nanodiscs show a modulation by the function (3 cos2 θ - 1), where θ is the angle between the N-H bond vector and the applied magnetic field direction. This successful demonstration of the use of two orthogonally oriented alignment media should enable structural studies on a variety of systems including small molecules, DNA, and RNA.

A Robust Method for the Large-Scale Production of Spheroids for High-Content Screening and Analysis Applications.

High-content screening (HCS) and high-content analysis (HCA) are technologies that provide researchers with the ability to extract large-scale quantitative phenotypic measurements from cells. This approach has proved powerful for deepening our understanding of a wide range of both fundamental and applied events in cell biology. To date, the majority of applications for this technology have relied on the use of cells grown in monolayers, although it is increasingly realized that such models do not recapitulate many of the interactions and processes that occur in tissues. As such, there has been an emergence in the development and use of 3-dimensional (3D) cell assemblies, such as spheroids and organoids. Although these 3D models are particularly powerful in the context of cancer biology and drug delivery studies, their production and analysis in a reproducible manner suitable for HCS and HCA present a number of challenges. The protocol detailed here describes a method for the generation of multicellular tumor spheroids (MCTS), and demonstrates that it can be applied to three different cell lines in a manner that is compatible with HCS and HCA. The method facilitates the production of several hundred spheroids per well, providing the specific advantage that when used in a screening regime, data can be obtained from several hundred structures per well, all treated in an identical manner. Examples are also provided, which detail how to process the spheroids for high-resolution fluorescence imaging and how HCA can extract quantitative features at both the spheroid level as well as from individual cells within each spheroid. This protocol could easily be applied to answer a wide range of important questions in cell biology.

Polymer Micro and Nanoparticles Containing B(III) Compounds as Emissive Soft Materials for Cargo Encapsulation and Temperature-Dependent Applications.

Polymer nanoparticles doped with fluorescent molecules are widely applied for biological assays, local temperature measurements, and other bioimaging applications, overcoming several critical drawbacks, such as dye toxicity, increased water solubility, and allowing imaging of dyes/drug delivery in water. In this work, some polymethylmethacrylate (PMMA), polyvinylpyrrolidone (PVP) and poly(styrene-butadiene-styrene) (SBS) based micro and nanoparticles with an average size of about 200 nm and encapsulating B(III) compounds have been prepared via the reprecipitation method by using tetrahydrofuran as the oil phase and water. The compounds are highly hydrophobic, but their encapsulation into a polymer matrix allows obtaining stable colloidal dispersions in water (3.39 µM) that maintain the photophysical behavior of these dyes. Although thermally activated non-radiative processes occur by increasing temperature from 25 to 80 °C, the colloidal suspension of the B(III) particles continues to emit greenish light (λ = 509 nm) at high temperatures. When samples are cooling back to room temperature, the emission is restored, being reversible. A probe of concept drug delivery study was conducted using coumarin 6 as a prototype of a hydrophobic drug.

Detailed comparison of anatomy and airflow dynamics in human and cynomolgus monkey nasal cavity

Nonhuman primates are occasionally used as laboratory models for sophisticated medical research as they bear the closest resemblance to humans in morphometry and physiological functions. A range of nonhuman primate species have been employed in the inhalation toxicity, nasal drug delivery and respiratory viral infection studies, and they provided valuable insight to disease pathogenesis while other laboratory animals such as rodents cannot recapitulate due to the lesser degree of similarity in metabolism, anatomy and cellular response to that of humans. It is anticipated that nonhuman primate models of respiratory diseases will continue to be instrumental for translating biomedical research for improvement of human health, and the confidence in laboratory data extrapolation between species will play a pivotal role. From the morphometry and flow dynamics point of view, this study performed a detailed comparative analysis between human and a cynomolgus monkey nasal airway, with intention to provide high-fidelity qualitative and quantitative linkage between the two species for more effective laboratory data extrapolation. The study revealed that cynomolgus monkey could be a good human surrogate in nasal inhalation studies; however, care should be given for interspecies data extrapolation as subtle differences in anatomy and airflow dynamics were present between the two species.

Ellagic acid as a potent anticancer drug: A comprehensive review on in vitro, in vivo, in silico, and drug delivery studies.

Ellagic acid as a polyphenol or micronutrient, which can be naturally found in different vegetables and fruits, has gained considerable attention for cancer therapy due to considerable biological activities and different molecular targets. Ellagic acid with low hydrolysis and lipophilic and hydrophobic nature is not able to be absorbed in circulation. So, accumulation inside the intestinal epithelial cells or metabolization to other urolithins leads to the limitation of direct evaluation of EA effects in clinical studies. This review focuses on the studies which supported anticancer activity of pure or fruit-extracted ellagic acid through in vitro, in vivo, in silico, and drug delivery methods. The results demonstrate ellagic acid modulates the expression of various genes incorporated in the cancer-related process of apoptosis and proliferation, inflammation related-gens, and oxidative-related genes. Moreover, the ellagic acid formulation in carriers composed of lipid, silica, chitosan, iron- bovine serum albumin nanoparticles obviously enhanced the stable release and confident delivery with minimum loss. Also, in silico analysis proved that ellagic acid was able to be placed at a position of cocrystal ADP, in the deep cavity ofthe protein target, and tightly interact with binding pocket residues leading to suppression of substrate availability of protein and its activation inhibition.

Maleimide-Functionalized Liposomes for Tumor Targeting via In Situ Binding of Endogenous Albumin.

Albumin, the most abundant protein in plasma, has been widely used in drug delivery studies. Here, we developed maleimide-functionalized liposomes (Mal-Lip) that can bind to endogenous albumin to improve the tumor targeting efficiency of liposomes. Transmission electron microscopy and gel electrophoresis studies showed that albumin can bind to Mal-Lip due to the chemical coupling of the albumin thiol groups with the maleimide group. Both conventional liposomes and Mal-Lip showed minimal cytotoxicity within the tested range of lipid concentrations, indicating that the maleimide functionality did not increase the toxicity of liposomes to various cells. Mal-Lip was taken up by 4T1 cells to a greater extent than conventional liposomes, and Mal-Lip accumulated in 4T1 tumors in mice more than conventional liposomes after intravenous injection. These results suggest that the maleimide group can improve the tumor targeting efficiency of liposomes in vivo by binding to endogenous albumin in situ. However, the maleimide group also enhanced the uptake of Mal-Lip by Raw264.7 cells and shortened their time in circulation, indicating that further studies should be performed to prevent elimination of Mal-Lip by the immune system.

Synthesis of Novel Tamarind Gum-co-poly(acrylamidoglycolic acid)-Based pH Responsive Semi-IPN Hydrogels and Their Ag Nanocomposites for Controlled Release of Chemotherapeutics and Inactivation of Multi-Drug-Resistant Bacteria.

In this paper, novel pH-responsive, semi-interpenetrating polymer hydrogels based on tamarind gum-co-poly(acrylamidoglycolic acid) (TMGA) polymers were synthesized using simple free radical polymerization in the presence of bis[2-(methacryloyloxy)ethyl] phosphate as a crosslinker and potassium persulfate as a initiator. In addition, these hydrogels were used as templates for the green synthesis of silver nanoparticles (13.4 ± 3.6 nm in diameter, TMGA-Ag) by using leaf extract of Teminalia bellirica as a reducing agent. Swelling kinetics and the equilibrium swelling behavior of the TMGA hydrogels were investigated in various pH environments, and the maximum % of equilibrium swelling behavior observed was 2882 ± 1.2. The synthesized hydrogels and silver nanocomposites were characterized via UV, FTIR, XRD, SEM and TEM. TMGA and TMGA-Ag hydrogels were investigated to study the characteristics of drug delivery and antimicrobial study. Doxorubicin hydrochloride, a chemotherapeutic agent successfully encapsulated with maximum encapsulation efficiency, i.e., 69.20 ± 1.2, was used in in vitro release studies in pH physiological and gastric environments at 37 °C. The drug release behavior was examined with kinetic models such as zero-order, first-order, Higuchi, Hixson Crowell and Korsmeyer–Peppas. These release data were best fitted with the Korsemeyer–Peppas transport mechanism, with n = 0.91. The effects of treatment on HCT116 human colon cancer cells were assessed via cell viability and cell cycle analysis. The antimicrobial activity of TMGA-Ag hydrogels was studied against Staphylococcus aureus and Klebsiella pneumonia. Finally, the results demonstrate that TMGA and TMGA-Ag are promising candidates for anti-cancer drug delivery and the inactivation of pathogenic bacteria, respectively.

TAMI-09. INTRAOPERATIVE MICRODIALYSIS AS A FEASIBLE PLATFORM FOR METABOLIC AND PHARMACODYNAMIC BIOMARKER DISCOVERY

Abstract BACKGROUND Progress for gliomas is slowed in part by the paucity of mechanistic feedback during treatment with experimental therapies. Access to extracellular tumor pharmacodynamic biomarkers could provide an avenue to accelerate progress. We have initiated a program of intra-operative microdialysis to accelerate biomarker discovery and to identify candidate outcome measures for translational therapies. METHODS Intraoperative microdialysis was performed with M-dialysis 100kDA catheters and 107 variable rate pumps under an IDE. Four IDH-mutant and two IDH-WT lesions were studied intraoperatively with 3 divergently placed catheters. Microperfusate (artifical CSF+ 3% dextran) was perfused at 2uL/min and collected in 20 min increments. Paired CSF was also obtained when accessible. A parallel cohort of nude mice bearing human IDH-mutant, IDH-WT, or sham intracranial xenografts (n=6-12) underwent intratumoral microdialysis. A pilot murine study of intracranial drug delivery was performed via concurrent microdialysis during convection-enhanced delivery (CED) of saline or the IDH-inhibitor AG120. RESULTS Microdialysate from IDH-mutant intracranial xenografts revealed &amp;gt;100 differentially abundant metabolites compared to sham or IDH-WT tumors, including D2-HG (21x) and MTA(18x), p&amp;lt; 10^-5. The most significantly abundant metabolite was DMA (4x, p&amp;lt; 10^-10). 15-1000uM D2HG was recovered from intra-operative human IDH-mutant tumors and 1-2uM from normal brain adjacent to IDH-WT gliomas and &amp;lt; 1uM in all IDH-WT samples. Forty metabolites differentiated enhancing tumor from adjacent brain in 3/3 paired human samples including upregulated Aminoacyl-tRNA biosynthesis and downregulated purine metabolism. Serial aliquots of microdialysate during saline CED yielded steady D2-HG levels whereas CED with AG120 yielded undetectable D2-HG within 6 hours. CONCLUSION The extracellular metabolic landscape of glioma is diverse, dynamic and reflects tumor biology and response to therapy. Collectively, these studies suggest that intra-tumoral drug testing should be feasible with realistic expectation of gaining metabolic feedback within a short timeframe. Leveraging this paradigm can provide opportunities to accelerate therapeutic translation for gliomas.

A Review of Gum Hydrocolloid Polyelectrolyte Complexes (PEC) for Biomedical Applications: Their Properties and Drug Delivery Studies

The utilization of natural gum polysaccharides as the vehicle for drug delivery systems and other biomedical applications has increased in recent decades. Their biocompatibility, biodegradability, and price are much cheaper than other materials. It is also renewable and available in massive amounts, which are the main reasons for its use in pharmaceutical applications. Gum can be easily functionalized with other natural polymers to enhance their applications. Various aspects of the utilization of natural gums in the forms of polyelectrolyte complexes (PECs) for drug delivery systems are discussed in this review. The application of different mathematical models were used to represent the drug release mechanisms from PECs; these models include a zero-order equation, first-order equation, Higuchi, simplified Higuchi, Korsmeyer–Peppas, and Peppas–Sahlin.