Single Syringe Research Articles

Multi-Stream Perfusion Bioreactor Integrated with Outlet Fractionation for Dynamic Cell Culture.

Certain cell and tissue functions operate within the dynamic time scale of minutes to hours that are poorly resolved by conventional culture systems. This work has developed a low-cost perfusion bioreactor system that allows culture medium to be continuously perfused into a cell culture module and fractionated in a downstream module to measure dynamics on this scale. The system is constructed almost entirely from commercially available parts and can be parallelized to conduct independent experiments in conventional multi-well cell culture plates simultaneously. This video article demonstrates how to assemble the base setup, which requires only a single multichannel syringe pump and a modified fraction collector to perfuse up to six cultures in parallel. Useful variants on the modular design are also presented that allow for controlled stimulation dynamics, such as solute pulses or pharmacokinetic-like profiles. Importantly, as solute signals travel through the system, they are distorted due to solute dispersion. Furthermore, a method for measuring the residence time distributions (RTDs) of the components of the perfusion setup with a tracer using MATLAB is described. RTDs are useful to calculate how solute signals are distorted by the flow in the multi-compartment system. This system is highly robust and reproducible, so basic researchers can easily adopt it without the need for specialized fabrication facilities.

(Digital Presentation) 3D Chocolate Printing for Shape and Texture Control

Food 3D printing is expected to be a technology to create foods with different tastes and hardness depending on individual preferences and to solve the problem of food loss problems. In this study, we focus on the 3D printing of chocolate, whose product value is greatly affected by its appearance, entertainment and texture. Although 3D printers of chocolate are gradually appearing in the market, most of them only focus on the modeling of shape, and there are quite few printers that can form chocolate with designed texture. We develop a chocolate 3D printer using two chocolate materials. In addition to the syringe type extruder, we introduce the gear pump type extruder, which has a fine and stable extrusion. We 3d print chocolates with various internal structures using two chocolate materials and evaluate the differences in their textures by equipment measurement and by sensory tests. In addition, the melt-in-mouth feeling and the snappiness, which are important for the texture of chocolate, are investigated. In this presentation, we report the results of texture tests of black chocolate formed by a single syringe type 3D printer.

Hotmelt tissue adhesive with supramolecularly-controlled sol-gel transition for preventing postoperative abdominal adhesion

Postoperative adhesion is a serious and frequent complication, but there is currently no reliable anti-adhesive barrier available due to low tissue adhesiveness, undesirable chemical reactions, and poor operability. To overcome these problems, we report a single-syringe hotmelt tissue adhesive that dissolves upon warming over 40 °C and coheres at 37 °C as a postoperative barrier. Tendon-derived gelatin was conjugated with the ureidopyrimidinone unit to supramolecularly control the sol-gel transition behavior. This functionalization improved bulk mechanical strength, tissue-adhesive properties, and stability under physiological conditions through the augmentation of intermolecular hydrogen bonding by ureidopyrimidinone unit. This biocompatible adhesive prevented postoperative adhesion between cecum and abdominal wall in adhesion models of rats. This hotmelt tissue adhesive has enormous potential to prevent postoperative complications and may contribute to minimally invasive surgery. Statement of significanceThere is a strong need to develop medical tissue adhesives with high biocompatibility, tissue adhesiveness, and operatability to prevent postoperative complications. In this report, single syringe, hotmelt-type tissue adhesive was developed by controlling sol-gel transition behavior of gelatin through supramolecular approach. The functionalization of gelatin with quadruple hydrogen bonding improved key features necessary for anti-adhesive barrier including bulk mechanical strength, tissue adhesive property, stability under physiological conditions, and anti-adhesive property. The hotmelt tissue adhesive can be used for a sealant, hemostatic reagent, and wound dressing to prevent postoperative complications including delayed bleeding, perforation, and inflammation and contribute to minimally invasive surgery.

Iron sulfate-reinforced hydrogel reactors with glucose deprivation, serial reactive oxygen species generation, ferroptosis induction, and photothermal ablation for cancer therapy

Glucose deprivation, hydroxyl radical generation, photothermal ablation, and ferroptosis induction-installed injectable hydrogel reactor was designed for multiple therapy of localized breast cancer. Iron sulfate (IS) was introduced to hydrogel reactor network for coordination with catechol groups of hyaluronic acid-catechol (HC) conjugate, photothermal conversion by reaction with catechols, Fenton-reaction-related hydroxyl radical production, and ferroptosis induction of cancer cells. Glucose oxidase (GOx) was incorporated in hydrogel reactor for the decomposition of glucose and production of H2O2. Following curing strategies were elaborately organized in the one-pot hydrogel reactor structure: i) starvation of cancer cells and self-supply of H2O2 by GOx, ii) hydroxyl radical generation (from H2O2) and ferroptosis induction by IS, and iii) photothermal therapy by catechol polymerization and iron ion-catechol binding. Exquisite arrangement of therapeutic modalities in HC-based hydrogel network by local injection to breast cancer was applied in this study. Also, the rheological properties of HC hydrogel were tuned by pH adjustment for endowing immediate and uniform gelation features, injection through single syringe, shear-thinning behaviors, and self-healing characteristics. It is expected that fabricated hydrogel reactor system can be used efficiently and safely for curing cancers following its local injection.

Therapeutic Treatment Plan Optimization during the COVID-19 Pandemic: A Comprehensive Physicochemical Compatibility Study of Intensive Care Units Selected Drugs

Background: The SARS-CoV-2 pandemic has resulted in a dramatic rise of the demand for medical devices and drugs. In this context, an important shortage of programmable syringe pumps, used to administrate different drugs in intensive care units, was seen. The opportunity of administrating combinations of five intensive care units selected drugs (Sufentanil, Clonidine, Loxapine, Midazolam, and Ketamine) was considered. Methods: The drug mixtures were studied in a pure form or diluted in NaCl 0.9% or G5%. Twenty-six possible combinations of the five drugs were produced in glass vials or polypropylene syringes and stored at 25 °C for 14 days. The LC method was implemented to study drugs combinations in the presence of the degradation products. The clearness and pH were also monitored. Results: All the 26 possible combinations displayed adequate physicochemical stability at 25 °C: at least 3 days and 7 days, respectively, for the dilution in 0.9% NaCl or glucose 5%, and the pure drug products mixtures. Conclusions: The study provided sufficient stability results, covering the medication administration period of at least three days. The combination of more than two drugs offers the advantage of minimizing the individual doses and reduces unwanted side-effects. Hence, this study opens up the possibility of combining the five drugs in one single syringe, which is useful especially under the current circumstances associated with an important shortage of programmable syringe pumps and pharmaceuticals.

Production and characterization of hybrid nanofiber wound dressing containing Centella asiatica coated silver nanoparticles by mutual electrospinning method

The aim of this work is to produce a therapeutic and antimicrobial nanofiber wound dressing material with suitable air permeability, water vapor transmission, water absorption, porosity, thermal and mechanical strength. For this purpose, first of all, Centella asiatica (CA) coated silver nanoparticles (CA-AgNPs) are synthesized with using CA extract as reducing and stabilizing agent. The green synthesized CA-AgNPs are characterized by UV–Vis spectroscopy, transmission electron microscope (TEM), zeta potential and fourier transform infrared (FTIR) spectroscopy measurements. The obtained CA-AgNPs give a single peak in the 420–430 nm range between 200 and 700 nm due to surface plasmon resonance (SPR). The average zeta potential and size of CA-AgNPs is found to be −30.4 mV and 14.8 ± 7.3 nm, respectively. Then, poly caprolactone (PCL) and polyethylene oxide (PEO) nanofibers composition containing CA-AgNPs is synthesized by mutual electrospinning method. Before electrospinning, the PCL solution (12% w/v in chloroform/methanol (70%/30%, v/v)), PEO solution (3.5%, w/v in water) and PEO solutions containing 1%, 5% and 10% (v:v) of CA-AgNPs are prepared. In electrospinning experiments, to synthesis the PCL/PEO nanofibers containing CA-AgNPs, an electrospinning set-up consisting of two high voltage sources, an aluminum rotary roller collector and two syringe pumps (one with a double syringe and the other with a single syringe) is used. To produce the wound dressing materials, PEO solutions containing CA-AgNPs are placed on the double syringe pump and PCL solution is placed on the single syringe pump. The surface and physico-chemical properties of the produced hybrid nanofibers are characterized by field emission scanning electron microscopy (FESEM), energy dispersion spectrometry (EDS), FTIR, X-ray diffractometer (XRD), Brunauer-Emmett-Teller (BET) surface area and porosity analyzer. Also, the thermal and mechanical properties of the obtained materials are investigated. In addition, the air permeability, water uptake capacity, water contact angle, water vapor transmission, in vitro degradation and silver release behavior of the samples are investigated. The results show that mutual dual-spinneret electrospinning technique combines the features of dissimilar components without corruption. Moreover, the in vitro degradation profile and silver release results show that these nanofibers could be used in wound dressing applications in the long term. With antimicrobial studies, PEO/PCL nanofibers containing 5% and 10% CA-AgNPs are found to be effective against Staphylococcus aureus, Escherichia coli and Candida albicans. Also, the cytotoxic properties of nanofibers are investigated by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay and results show the good biocompatibility for L929 fibroblast cells. Results reveal that CA-AgNPs loaded PCL/PEO hybrid nanofibers materials synthesized in this study has a promising potential for wound healing applications.

Abstract 10470: Comparison Between the Double-Syringe Technique and the Single-Syringe Diluted with Normal Saline Technique of Adenosine for a Termination of Supraventricular Tachycardia: A Pilot, Randomized, Single-Blind Controlled Trial (Do-Single Trial)

Introduction: Supraventricular tachycardia (SVT) is a condition commonly found in emergency settings. Adenosine is recommended as the first-line treatment for stable patients, however, it is rapidly metabolized. The ACLS guidelines recommend administration of 6-mg adenosine intravenously (IV) with an immediate 20-ml normal saline solution (NSS) IV (double syringe technique; DST). However, adenosine diluted with NSS up to 20 ml IV (single syringe technique; SST) was as well found effective for terminating the arrhythmia. Hypothesis: The SST is non-inferior to the DST for terminating stable SVT. Methods: A pilot, single-blind, randomized, controlled study was conducted from January to December 2020 at 4 hospitals in the northeastern region, Thailand. Thirty patients who presented with stable regular narrow complex tachycardia, diagnosed as stable SVT by cardiologists, were enrolled. They were randomized into the DST and SST groups, 15 patients each. We evaluated the termination of SVT (turned to normal sinus rhythm), the average successful doses, and the complication rate of each group. Analyses were based on the intention to treat principle. Results: The termination rate was 91.7% and 83.3% in the DST and the SST group, P =0.990. The success rate of 6-mg adenosine was 75% and 66.7% in the DST and the SST group, P =0.640. The total administration dose was 8.2±4.9 mg in the DST group, and 10.0±5.9 mg in the SST group, P =0.432. There was no difference in the complication rate between both groups. Conclusions: Adenosine diluted with NSS up to 20 ml administered IV was non-inferior to the conventional technique for terminating SVT. A further definitive study with larger sample size is required.

Assessment of intramuscular administration of three doses of alfaxalone combined with hydromorphone and dexmedetomidine for endoscopic-guided orotracheal intubation in domestic rabbits (Oryctolagus cuniculus).

To determine the dose of alfaxalone for IM administration combined with dexmedetomidine and hydromorphone that would allow endoscopic-guided orotracheal intubation in rabbits without causing a decrease in respiratory rate or apnea. 15 sexually intact (9 females and 6 males) healthy Miniature Lop rabbits weighing a mean ± SD of 2.3 ± 0.3 kg and ranging in age from 4 to 9 months. In a randomized, controlled clinical trial, rabbits received 0.1 mg of hydro-morphone/kg and 0.005 mg of dexmedetomidine/kg, plus alfaxalone at either 2 mg/kg (5 rabbits), 5 mg/kg (5 rabbits), or 7 mg/kg (5 rabbits). Drugs were mixed in a single syringe and administered IM. Semiquantitative rating scales were used to evaluate quality of anesthesia and intubation. Orotracheal intubation was attempted with endoscopy and confirmed by capnography. The number of successful intubations was 0, 3, and 4 in rabbits receiving 2, 5, and 7 mg of alfaxalone/kg, respectively. Median (range) anesthesia quality scores (scale, 0 to 12; 12 = deepest anesthesia) were 3 (2 to 5), 6 (5 to 6), and 6 (4 to 9) for rabbits receiving 2, 5, and 7 mg of alfaxalone/kg, respectively. The median (range) intubation quality scores (scale, 0 to 3 [ie, intubation not possible to easiest intubation]) were 0 (0 to 0), 2 (0 to 3), and 2 (0 to 3) for rabbits receiving 2, 5, and 7 mg of alfaxalone/kg, respectively. None of the rabbits experienced a decrease in respiratory rate or apnea. Increasing doses of alfaxalone combined with hydromorphone and dexmedetomidine increased the success rate of endoscopic-guided orotracheal intubation. Increasing the dose of alfaxalone had no effect on respiratory rate.

Safety and immunogenicity of a multidose vial formulation of 13-valent pneumococcal conjugate vaccine administered with routine pediatric vaccines in healthy infants in India: A phase 4, randomized, open-label study

PurposeThis phase 4, randomized, open-label, multicenter study in healthy Indian infants and toddlers evaluated the safety, tolerability, and immunogenicity of the 13-valent pneumococcal conjugate vaccine (PCV13) formulated in a multidose vial (MDV) or single prefilled syringe (PFS). MethodsHealthy Indian infants (6 weeks of age) were randomized 1:1 to receive either PCV13-MDV or PCV13-PFS concomitant with routine pediatric vaccines. Subjects received a single dose of either PCV13-MDV or PCV13-PFS as a 4-dose schedule (infant series: 1 dose at 6, 10, and 14 weeks of age; toddler dose: 12 months of age). Safety was assessed, including local reactions, systemic events, and adverse events (AEs). Immunogenicity 1 month after both the infant series and toddler dose was measured by concentrations of serotype-specific immunoglobulin G (IgG) antibodies and opsonophagocytic activity titers. ResultsRates and severities of local reactions and systemic events up to 7 days after each dose of either PCV13-MDV or PCV13-PFS were generally similar, with the majority being of mild or moderate severity. PCV13-MDV had a safety profile comparable with PCV13-PFS; both groups experienced a similar frequency of AEs. PCV13-MDV elicited immune responses comparable with those induced by PCV13-PFS. Clear boosting of immune responses after the PCV13-MDV toddler dose was observed; ≥96% of subjects showed serotype-specific IgG concentrations at or above the defined thresholds 1 month after the PCV13-MDV toddler dose. ConclusionsPCV13-MDV was safe, well tolerated, and immunogenic in healthy Indian infants and toddlers when coadministered with routine pediatric vaccinations. Safety and immunogenicity of PCV13-MDV was comparable with PCV13-PFS. Clinical Trial RegistrationClinicaltrials.gov: NCT03548337.

Clinical Knowledge and Practice of "Ketofol" at University of Gondar Comprehensive Specialized Hospital.

Background: Ketamine and propofol in a single syringe are reported to create an admixture used for balancing cardiorespiratory effects during induction of general anesthesia. This study aimed to assess the clinical practice and knowledge of “ketofol” among anesthesia providers.Methods: A cross-sectional institutional-based study was conducted among anesthesia providers. Data abstracted format was prepared and distributed to senior anesthetists, junior anesthetist postgraduate students, and undergraduate students. The study was conducted from January 1, 2019, to January 30, 2019. Descriptive statistics and binary logistic regression were performed for frequency distribution and to determine the association, respectively.Result: From a total of 133 participants included in the study, the majority, 88 (66.2%), were men and 75 (56.9%) had 0–2 years of experience. More than two-thirds of participants, 105 (78.9%), have never had a seminar or educational session about combined use. Lack of experience among 11 participants (8.3%) was one of the reasons for not using “ketofol” followed by lack of knowledge among three (2.3%) participants. The majority of participants, 112 (84.2%), prefer ketamine and propofol to be administered one right after the other with separate syringes and the ratio to be 1:2, 64 (48.2). There was no significant association observed between sociodemographic and other characteristics and the practice of “ketofol.”Conclusion: In this study, nearly half of the participants rated their knowledge at the average level, and the study identifies that there is clinical knowledge and practice gap among anesthesia providers working in the University of Gondar Comprehensive Specialized Hospital (UOGCSH). Preparing educational sessions regarding “ketofol” for addressing identified barriers is among the recommendations forwarded to UOGCSH.

Dual-Light-Triggered In Situ Structure and Function Regulation of Injectable Hydrogels for High-Efficient Anti-Infective Wound Therapy.

Most injectable hydrogels used in biomedical engineering have unsatisfactory and untunable mechanical properties, making it difficult to match them with the mechanical strengths of different tissues and organs, which can cause a series of adverse consequences such as immune rejection and soft tissue contusion. In this contribution, dopamine-modified hyaluronic acid (HA-DA) is developed as the backbone for an injectable hydrogel using a catechol-Fe3+ coordination crosslinking strategy. Due to dynamic physical crosslinking, the hydrogel can be easily injected through a single syringe. Into the hydrogel, black phosphorous nanosheets loaded with a Zr-based porphyrinic metal-organic framework (PCN@BP) are introduced that could generate reactive oxygen species (ROS) under 660nm laser irradiation, this promotes the oxidative coupling of dopamine in the presence of the ROS, introducing in situ chemical crosslinking into the hydrogel. A physical/chemical double-crosslinked hydrogel is obtained, effectively improving the hydrogel's mechanical properties, which are tuned in situ by adjusting the irradiation time to match the mechanical modulus of different biological tissues. Combining the excellent photothermal properties and photodynamic performance of the PCN@BP nanosheets yields effective sterilization under mild conditions (below 50 °C, low ROS production). The results show that this hydrogel is an excellent multifunctional wound dressing.

Dupilumab (Dupixent)

CADTH reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class. The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada's federal, provincial, and territorial governments, with the exception of Quebec. This review assesses dupilumab (Dupixent), 200 mg or 300 mg, single use syringe, solution for subcutaneous injection. Indication: As add-on maintenance treatment in patients aged 12 years and older with severe asthma with a type 2/eosinophilic phenotype or oral corticosteroid–dependent asthma Reimbursement request: For patients with type 2 or eosinophilic asthma characterized by the following: 2 or more clinically significant asthma exacerbations in the last 12 months and blood eosinophils ≥ 150 cells/µL, or fractional exhaled nitric oxide ≥ 25 parts per billion, or treatment with maintenance oral corticosteroids, or clinically allergen-driven asthma.

Opioid-Free Anesthesia: Physico Chemical Stability Studies on Multi-Analyte Mixtures Intended for Use in Clinical Anesthesiology

Objectives: Opioid-free anesthesia is used increasingly often in hospitals around the world. In this type of anesthesia, opioids are replaced by other analgesics, such as ketamine, lidocaine, dexmedetomidine, and magnesium sulfate. Many clinicians prepare these agents as dual, triple, or quadruple admixtures within a single syringe. However, data on the stability of the individual substances within these preparations over time and in different storage conditions is very limited. Here, we aim to investigate various admixture of dexmedetomidine, ketamine, lidocaine, and magnesium sulfate with respect to the stability of the individual agents over time at different storage conditions. Methods: An ultra-high performance liquid chromatography method coupled to mass spectrometric detection was developed and validated to determine the stability of lidocaine, ketamine, and dexmedetomidine. Quantification of magnesium was carried out in parallel by potentiometric titration. Results: Our results demonstrate the stability of dual, triple or quadruple mixtures of selected substances in 0.9% saline under different storage conditions. Under all conditions, analyzed admixtures remain stable for at least 8 weeks. The quadruple mixture of lidocaine, ketamine, dexmedetomidine, and magnesium sulfate was storable for as long as 148 days without a significant loss of analyte. Conclusion: A new chromatographic method was successfully developed to analyze the stability of various pharmacological agents commonly used by clinicians in opioid-free anesthesia. The data we obtained indicate that mixing these agents together in a single syringe is safe and reliable and suggest that hospital pharmacies may prepare these solutions in advance of planned surgeries.

Polypseudorotaxane and polydopamine linkage-based hyaluronic acid hydrogel network with a single syringe injection for sustained drug delivery

Polypseudorotaxane structure and polydopamine bond-based crosslinked hyaluronic acid (HA) hydrogels including donepezil-loaded microspheres were developed for subcutaneous injection. Both dopamine and polyethylene glycol (PEG) were covalently bonded to the HA polymer for catechol polymerization and inclusion complexation with alpha-cyclodextrin (α-CD), respectively. A PEG chain of HA-dopamine-PEG (HD-PEG) conjugate was threaded with α-CD to make a polypseudorotaxane structure and its pH was adjusted to 8.5 for dopamine polymerization. Poly(lactic-co-glycolic acid) (PLGA)/donepezil microsphere (PDM) was embedded into the HD-PEG network for its sustained release. The HD-PEG/α-CD/PDM 8.5 hydrogel system exhibited an immediate gelation pattern, injectability through single syringe, self-healing ability, and shear-thinning behavior. Donepezil was released from the HD-PEG/α-CD/PDM 8.5 hydrogel in a sustained pattern. Following subcutaneous injection, the weight of excised HD-PEG/α-CD/PDM 8.5 hydrogel was higher than the other groups on day 14. These findings support the clinical feasibility of the HD-PEG/α-CD/PDM 8.5 hydrogel for subcutaneous injection.

Three-in-one via syringe needle-based device: sampling, microextraction and peroxidase-like catalysis for colorimetric detection of the change of biogenic amines levels with time in meat

In this work, a syringe needle-based integrated method was designed for the detection of biogenic amines (BAs) in raw meat samples. Based on a sequential process, the needle-based sampling, micro liquid-phase extraction and peroxidase-like catalysis were adopted for the sample collection, target analytes extraction and colorimetric analysis, respectively. The proposed method exhibited high selectivity towards BAs (the total amount of histamine, putrescine and cadaverine was utilized to present the level of BAs), where the linear range is 5–50 μM and 50–1000 μM, and the limit of detection is 1.52 μM. Specifically, the whole process could be completed in a single syringe needle. In addition, due to the minimized sampling, the change of BAs levels with time in different area of real samples (fish) can be conveniently investigated. This method has the advantages of simplicity, low cost, high sensitivity and selectivity, endowing it a promising candidate for food analysis.

Low-cost, programmable infusion pump with bolus mode for in-vivo imaging

Syringe pumps are routinely used in biomedical imaging laboratories for delivering contrast agents and either infusing or injecting a precise amount of liquids. Commercial syringe pumps that are developed by specialized companies are expensive and only have standard functions, which often do not meet the requirements of individual experiments. In this paper, we demonstrate an open–source single syringe pump with the possibility of adapting to the needs of a researcher. The device that was designed, is controlled by an Arduino Leonardo, along with the stepper motor driver. For sending commands and receiving the current plunger position, a C# software was developed with serial communication via USB. Additionally, the 3D models were made in a universal way, which allows for the use of any syringe size. An example of the application of the syringe pump for biomedical applications was demonstrated using electron resonance imaging (ERI). The single syringe pump tests were demonstrated by simulating the filling of a particular volume inside the resonator. This example reflects the clearance process after an intravascular (I.V) drug administration in the murine model. The experiments were performed on an ERI TM 600 tomograph. The results confirmed that the designed syringe pump allowed for controlling the infusion speed and injected volume. Moreover, we present a user-friendly and open-source graphical interface that is a low-cost alternative for commercial devices.

Comparison of ketofol versus propofol for procedural sedation and analgesia in cervical cancer brachytherapy: A prospective, randomized double blind study

Most common drug used for outpatient procedural sedation and analgesia is propofol, with limitations like systemic hypotension. Combining propofol with ketamine preserves sedation efficacy, minimizing their respective adverse effects. So, we aimed to compare ketofol (ketamine+propofol) versus propofol regarding their total drug consumption, recovery profile, effect on haemodynamic and respiratory parameters in brachytherapy patients. A prospective, randomized, controlled double blind study was carried out in 100 female patients between 20-60 years, 30-70kg, ASA I-III undergoing brachytherapy as outpatient procedure on elective basis, after ethical clearance from institutional committee. These were randomly divided into 2 groups (50 each). Group P-Injpropofol (10mg/ml) 2mg/kg for induction and 20mg as supplementation. Group K-Injketofol (10mg/ml) (ketamine 50mg+propofol 100mg, 1:2) 2mg/kg for induction and 20 mg as supplementation.The supplementation dose required was significantly higher in propofol group (800mg) as compared to ketofol group (20mg) (p=0.00). Also, the fall in SBP and DBP was significantly less in ketofol group than propofol group (p<0.01). The mean awakening time (time from end of procedure to MRSS =3) andmean recovery time (time from end of procedure to achievement of Aldrete score 10) was more in ketofol group than propofol group (p<0.003), the difference was less than 1-2 min, so it was clinically not significant. Ketamine-propofol combination in 1:2 ratio in a single syringe as ketofolis better alternative to propofol in providing sedation and analgesia with better haemodynamic stability, for outpatient brachytherapy procedure in cancer cervix patients.

Serially pH-Modulated Hydrogels Based on Boronate Ester and Polydopamine Linkages for Local Cancer Therapy.

Elaborately and serially pH-modulated hydrogels possessing optimized viscoelastic natures for short gelation time and single syringe injection were designed for peritumoral injection of an anticancer agent. Boronate ester bonds between phenylboronic acid (PBA) (installed in HA-PBA (HP)) and dopamine (included in HA-dopamine (HD)) along with self-polymerization of dopamine (via interactions between HD conjugates) were introduced as the main cross-linking strategies of a hyaluronic acid (HA) hydrogel. Considering pKa values (8.0-9.5) of PBA and dopamine, the pH of each polymer dispersion was controlled elaborately for injection through a single syringe, and the final pH was tuned nearby the physiological pH (pH 7.8). The shear-thinning behavior, self-healing property, and single syringe injectability of a designed hydrogel cross-linked nearby physiological pH may provide its convenient application to peritumoral injection and prolonged retention in local cancer therapy. Erlotinib (ERT) was encapsulated in a microsphere (MS), and it was further embedded in an HP/HD-based hydrogel for sustained and locoregional delivery. A rheologically tuned hydrogel containing an ERT MS exhibited superior tumor-suppressive efficiencies compared to the other groups in A549 tumor-bearing mice. A designed injectable hydrogel through a single syringe system may be efficiently applied to local cancer therapy with lower toxicities to healthy organs.

Fenton-like reaction, glutathione reduction, and photothermal ablation-built-in hydrogels crosslinked by cupric sulfate for loco-regional cancer therapy.

Fenton-like reaction-associated chemodynamic therapy (CDT) and hyperthermia-inducing photothermal therapy (PTT)-combined crosslinked hydrogel systems were developed for loco-regional cancer therapy. Cupric sulfate (Cu) has been employed to crosslink the catechol-functionalized hyaluronic acid (HC) polymer-based gel via metal-catechol coordination and covalent bonding of the catechol group (by pH adjustment). Cu can also be used as a hydroxyl radical-generating agent with endogenous H2O2 in cancer cells mediated by Fenton-like reaction and it can reduce intracellular glutathione (GSH) levels leading to the inhibition of reactive oxygen species (ROS) scavenging. These two strategies can amplify the ROS-initiated CDT efficiency for combating cancer. The Cu-incorporated crosslinked hydrogel structure with pH modulation was appropriate for injectable gel formation via a single syringe. The incorporation of indocyanine green (ICG) into the hydrogel network and near-infrared (NIR) laser irradiation provided a temperature elevation sufficient for induction of hyperthermia in cancer therapy. It is expected that the designed HC/Cu/ICG hydrogel can be used safely and efficiently for local CDT and PTT of breast cancer.

Loading Mg<sup>2+</sup> into Erythrocytes with a Proposed Single Syringe Sterile Loading Process

Purpose: Primary hypomagnesemia with secondary hypocalcemia (PHSH) is a genetically defined disease in which there is a malabsorption of magnesium from the intestine. The aim of this research was to encapsulate magnesium into autologous erythrocytes to be used in PHSH patients. A scheme to use a single syringe closed sterile system for the process is proposed. Controlled lysis of erythrocytes and the ability to reseal the loaded erythrocytes were investigated. Method: Suitable concentrations of salt solutions required for making reversible pores and resealing of erythrocytes were identified. For making reversible pores, 0.7% NaCl and 2.3% MgSO4 were used separately. A solution of 3.5% MgSO4 was used as the drug loading solution. After the loading step, the isotonicity for the erythrocytes was restored with 0.9% NaCl and 3.0% MgSO4 solutions separately. The ability to load and reseal erythrocytes were assessed by determining the resulting Mg2+ concentration through Microwave Plasma Atomic Emission Spectrophotometric (MP-AES) analysis. Results: Analysis of results revealed that Mg2+ ions can be successfully loaded into erythrocytes through the formation of reversible pores. Resealing failed with 3.0% MgSO4, but the erythrocytes were successfully resealed with 0.9% NaCl solution. Conclusion: The need for strictly controlled salt solution concentrations for lysis and resealing were identified. In theoretical concentration determinations, the osmotic coefficient had to be taken into account. The study showed the possibility of loading Mg2+ into erythrocytes as a successful drug delivery system.