Search results for: implant assisted-magnetic drug targeting (IA-MDT)

Authors: Vijayakameswara Rao Neralla, Jueun Jeon, Jae Hyung Park

Abstract:

To develop a potential nanocarrier for diagnosis and treatment of rheumatoid arthritis (RA), we prepared a hyaluronic acid (HA)-5β-cholanic acid (CA) conjugate with an acid-labile ketal linker. This conjugate could self-assemble in aqueous conditions to produce pH-responsive HA-CA nanoparticles as potential carriers of the anti-inflammatory drug methotrexate (MTX). MTX was rapidly released from nanoparticles under inflamed synovial tissue in RA. In vitro cytotoxicity data showed that pH-responsive HA-CA nanoparticles were non-toxic to RAW 264.7 cells. In vivo biodistribution results confirmed that, after their systemic administration, pH-responsive HA-CA nanoparticles selectively accumulated in the inflamed joints of collagen-induced arthritis mice. These results indicate that pH-responsive HA-CA nanoparticles represent a promising candidate as a drug carrier for RA therapy.

Keywords: rheumatoid arthritis, hyaluronic acid, nanocarrier, self-assembly, MTX

Procedia PDF Downloads 289

Authors: Mihika Shivkumar, Krishna Kumar, C. Perisamy

Abstract:

3D printing is a method of manufacturing wherein materials, such as plastic or metal, are deposited in layers one on top of the other to produce a three dimensional object. 3D printing is most commonly associated with creating engineering prototypes. However, its applications in the field of human health care have been frequently disregarded. Medical applications for 3D printing are expanding rapidly and are envisaged to revolutionize health care. Medical applications for 3D printing, both present and its potential, can be categorized broadly, including: creation of customized prosthetics tissue and organ fabrication; creation of implants, and anatomical models and pharmaceutical research regarding drug dosage forms. This piece breaks down bioprinting in the healthcare sector. It focuses on the better subtle elements of every particular point, including how 3D printing functions in the present, its impediments, and future applications in the health care sector.

Keywords: bio-printing, prototype, drug delivery, organ regeneration

Procedia PDF Downloads 271

Authors: Fakhreldin O. Suliman, Alia H. Al-Battashi

Abstract:

This work explored the interaction of three different imidazoline drugs, naphazoline nitrate (NPH), oxymetazoline hydrochloride (OXY) and xylometazoline hydrochloride (XYL) with two different synthesized cucurbit[n]urils CB[n], cucurbit[7]uril (CB[7]) and cucuribit[8]uril (CB[8]). Three binary inclusion complexes have been investigated in solution and in the solid state. The solid complexes were obtained by lyophilization, whereas the physical mixtures of guests and hosts at a stoichiometric ratio of 1:1 were obtained for each drug. 1HNMR, electrospray ionization mass spectrometry (ESI-MS), and matrix-assisted laser desorption-ionization time-of-flight (MALDI-TOF) mass spectrometry was used to study the complexes prepared in aqueous media. The lyophilized solid complexes were characterized by Fourier transform-infrared spectroscopy (FT-IR), powder X-ray diffractometry (PXRD), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). MS, FT-IR and PXRD experimental results established in this work reveal that NPH, OXY and XYL molecules form stable inclusion complexes with the two hosts. The TGA and DSC confirmed the enhancement of the thermal stability of each drug and the production of a thermally stable solid complex. The 1HNMR has shown that the protons of the guests faced shifting in ppm and broadening of their peaks upon the formation of inclusion complexes with the selected CB[n]. The aromatic protons of the guest exhibited the highest changes in the chemical shifts and shape of the NMR peaks, suggesting their inclusion into the cavity of the CB[n]. The diffusion coefficients (D), developed from the diffusion-controlled NMR Spectroscopy (DOSY) measurements, for the complexation of the selected imidazoline drugs with CB[7] and CB[8], were decreased in the presence of hosts compared to the free guests indicating the formation of the guest-host adduct. Furthermore, we conducted molecular dynamic simulations and quantum mechanics calculations on these complexes. The results of the theoretical study corroborate the experimental findings and have also shed light on the mechanism of inclusion of the guests into the two hosts. This study generates initial data for potential drug delivery or drug formulation systems for these three selected imidazoline drug compounds based on their inclusion into the CB[n] cavities.

Keywords: cucurbit[n]urils, imidazoline, inclusion complexes, molecular dynamics, DFT calculations, mass spectrometry

Procedia PDF Downloads 68

Authors: Rachmat Mauludin, Nurmazidah

Abstract:

Background and purpose: Famotidine is an H2 receptor blocker. Absorption orally is rapid enough, but famotidine can be degraded by stomach acid causing dose reduction until 35.8% after 50 minutes. This drug also undergoes first-pass metabolism which reduced its bio availability only until 40-50%. To overcome these problems, Solid Lipid Nano particles (SLNs) as alternative delivery systems can be formulated. SLNs is a lipid-based drug delivery technology with 50-1000 nm particle size, where the drug incorporated into the bio compatible lipids and the lipid particles are stabilized using appropriate stabilizers. When the particle size is 200 nm or below, lipid containing famotidine can be absorbed through the lymphatic vessels to the subclavian vein, so first-pass metabolism can be avoided. Method: Famotidine SLNs with various compositions of stabilizer was prepared using a high-speed homogenization and sonication method. Then, the particle size distribution, zeta potential, entrapment efficiency, particle morphology and in vitro release profiles were evaluated. Optimization of sonication time also carried out. Result: Particle size of SLN by Particle Size Analyzer was in range 114.6 up to 455.267 nm. Ultrasonicated SLNs within 5 minutes generated smaller particle size than SLNs which was ultrasonicated for 10 and 15 minutes. Entrapment efficiency of SLNs were 74.17 up to 79.45%. Particle morphology of the SLNs was spherical and distributed individually. Release study of Famotidine revealed that in acid medium, 28.89 up to 80.55% of famotidine could be released after 2 hours. Nevertheless in basic medium, famotidine was released 40.5 up to 86.88% in the same period. Conclusion: The best formula was SLNs which stabilized by 4% Poloxamer 188 and 1 % Span 20, that had particle size 114.6 nm in diameter, 77.14% famotidine entrapped, and the particle morphology was spherical and distributed individually. SLNs with the best drug release profile was SLNs which stabilized by 4% Eudragit L 100-55 and 1% Tween 80 which had released 36.34 % in pH 1.2 solution, and 74.13% in pH 7.4 solution after 2 hours. The optimum sonication time was 5 minutes.

Keywords: famotodine, SLN, high speed homogenization, particle size, release study

Procedia PDF Downloads 860

Authors: E. G. Karvelas, C. Liosis, A. Theodorakakos, T. E. Karakasidis

Abstract:

Magnetic navigation of the drug inside the human vessels is a very important concept since the drug is delivered to the desired area. Consequently, the quantity of the drug required to reach therapeutic levels is being reduced while the drug concentration at targeted sites is increased. Magnetic navigation of drug agents can be achieved with the use of magnetic nanoparticles where anti-tumor agents are loaded on the surface of the nanoparticles. The magnetic field that is required to navigate the particles inside the human arteries is produced by a magnetic resonance imaging (MRI) device. The main factors which influence the efficiency of the usage of magnetic nanoparticles for biomedical applications in magnetic driving are the size and the magnetization of the biocompatible nanoparticles. In this study, a computational platform for the simulation of the optimal gradient magnetic fields for the navigation of magnetic nanoparticles inside a carotid artery is presented. For the propulsion model of the particles, seven major forces are considered, i.e., the magnetic force from MRIs main magnet static field as well as the magnetic field gradient force from the special propulsion gradient coils. The static field is responsible for the aggregation of nanoparticles, while the magnetic gradient contributes to the navigation of the agglomerates that are formed. Moreover, the contact forces among the aggregated nanoparticles and the wall and the Stokes drag force for each particle are considered, while only spherical particles are used in this study. In addition, gravitational forces due to gravity and the force due to buoyancy are included. Finally, Van der Walls force and Brownian motion are taken into account in the simulation. The OpenFoam platform is used for the calculation of the flow field and the uncoupled equations of particles' motion. To verify the optimal gradient magnetic fields, a covariance matrix adaptation evolution strategy (CMAES) is used in order to navigate the particles into the desired area. A desired trajectory is inserted into the computational geometry, which the particles are going to be navigated in. Initially, the CMAES optimization strategy provides the OpenFOAM program with random values of the gradient magnetic field. At the end of each simulation, the computational platform evaluates the distance between the particles and the desired trajectory. The present model can simulate the motion of particles when they are navigated by the magnetic field that is produced by the MRI device. Under the influence of fluid flow, the model investigates the effect of different gradient magnetic fields in order to minimize the distance of particles from the desired trajectory. In addition, the platform can navigate the particles into the desired trajectory with an efficiency between 80-90%. On the other hand, a small number of particles are stuck to the walls and remains there for the rest of the simulation.

Keywords: artery, drug, nanoparticles, navigation

Procedia PDF Downloads 107

Authors: Sarwar Beg, Gajanand Sharma, O. P. Katare, Bhupinder Singh

Abstract:

The current studies entail development of self-nano emulsifying drug delivery systems (SNEDDS) of rosuvastatin, employing rational QbD-based approach for enhancing its oral bioavailability. SNEDDS were prepared using the blend of lipidic and emulsifying excipients, i.e., Peceol, Tween 80, and Transcutol HP. The prepared formulations evaluated for in vitro drug release, ex vivo permeation, in situ perfusion studies and in vivo pharmacokinetic studies in rats, which demonstrated 3-4 fold improvement in biopharmaceutical performance of the developed formulations. Cytotoxicity studies using MTT assay and histopathological studies in intestinal cells revealed the lack of cytotoxicity and thereby safety and efficacy of the developed formulations.

Keywords: SNEDDS, bioavailability, solubility, Quality by Design (QbD)

Procedia PDF Downloads 505

Authors: Gail Louw, Helena Boshoff, Taeksun Song, Clifton Barry

Abstract:

Drug resistance in Mycobacterium tuberculosis is primarily attributed to mutations in target genes. These mutations incur a fitness cost and result in bacterial generations that are less fit, which subsequently acquire compensatory mutations to restore fitness. We hypothesize that mutations in specific drug target genes influence bacterial metabolism and cellular function, which affects its ability to develop subsequent resistance to additional agents. We aim to determine whether the sequential acquisition of drug resistance and specific mutations in a well-defined clinical M. tuberculosis strain promotes or limits the development of additional resistance. In vitro mutants resistant to pretomanid, linezolid, moxifloxacin, rifampicin and kanamycin were generated from a pan-susceptible clinical strain from the Beijing lineage. The resistant phenotypes to the anti-TB agents were confirmed by the broth microdilution assay and genetic mutations were identified by targeted gene sequencing. Growth of mono-resistant mutants was done in enriched medium for 14 days to assess in vitro fitness. Double resistant mutants were generated against anti-TB drug combinations at concentrations 5x and 10x the minimum inhibitory concentration. Subsequently, mutation frequencies for these anti-TB drugs in the different mono-resistant backgrounds were determined. The initial level of resistance and the mutation frequencies observed for the mono-resistant mutants were comparable to those previously reported. Targeted gene sequencing revealed the presence of known and clinically relevant mutations in the mutants resistant to linezolid, rifampicin, kanamycin and moxifloxacin. Significant growth defects were observed for mutants grown under in vitro conditions compared to the sensitive progenitor. Mutation frequencies determination in the mono-resistant mutants revealed a significant increase in mutation frequency against rifampicin and kanamycin, but a significant decrease in mutation frequency against linezolid and sutezolid. This suggests that these mono-resistant mutants are more prone to develop resistance to rifampicin and kanamycin, but less prone to develop resistance against linezolid and sutezolid. Even though kanamycin and linezolid both inhibit protein synthesis, these compounds target different subunits of the ribosome, thereby leading to different outcomes in terms of fitness in the mutants with impaired cellular function. These observations showed that oxazolidinone treatment is instrumental in limiting the development of multi-drug resistance in M. tuberculosis in vitro.

Keywords: oxazolidinones, mutations, resistance, tuberculosis

Procedia PDF Downloads 162

Authors: Bhumika Wadhwa, Fayaz Malik

Abstract:

The serine/threonine protein kinase B (PKB) also known as Akt, is one of the multifaceted kinase in human kinome, existing in three isoforms. Akt plays a vital role in phosphoinositide 3-kinase (PI3K) mediated oncogenesis in various malignancies and is one of the attractive targets for cancer drug discovery. The functional significance of an individual isoform of Akt is not redundant in cancer cell proliferation and metastasis instead Akt isoforms play distinct roles during metastasis; thereby regulating EMT. This study aims to determine isoform specific functions of Akt in cancer. The results obtained suggest that Akt1 restrict tumor invasion, whereas Akt2 promotes cell migration and invasion by various techniques like MTT, wound healing and invasion assay. Similarly, qRT-PCR also revealed that Akt3 has shown promising results in promoting cancer cell migration. Contrary to pro-oncogenic properties attributed to Akt, it is to be understood how various isoforms of Akt compensates each other in the regulation of common pathways during cancer progression and drug resistance. In conclusion, this study aims to target selective isoforms which is essential to inhibit cancer. However, the question now is whether, and how much, Akt inhibition will be tolerated in the clinic remains to be answered and the experiments will have to address the question of which combinations of newly devised Akt isoform specific inhibitors exert a favourable therapeutic effect in in vivo models of cancer to provide the therapeutic window with minimal toxicity.

Keywords: Akt isoforms, cancer, drug resistance, epithelial mesenchymal transition

Procedia PDF Downloads 256

Authors: Kwanputtha Arunprasert, Chaiyakarn Pornpitchanarong, Praneet Opanasopit, , Prasopchai Patrojanasophon

Abstract:

Capsaicin, a recently FDA-approved drug for the topical treatment of neuropathic pain, is associated with several side effects like burning sensation and erythema leading to severe skin irritation and poor patient compliance. These unwanted side effects are due to the rapid penetration of capsaicin into the epidermis and low permeation to the dermis layer. The purpose of this study was to develop nanostructured lipid carriers (NLCs) that entrapped capsaicin for reducing dermal irritation. Solid lipid (glyceryl monostearate (GM), cetyl palmitate (CP), cetyl alcohol (COH), stearic acid (SA), and stearyl alcohol (SOH)) and surfactant (Tween®80, Tween®20, and Span®20) were varied to obtained optimal capsaicin-loaded NLCs. The formulation using CP as solid lipid and Tween®80 as a surfactant (F2) demonstrated the smallest size, excellent colloidal stability, and narrow range distribution of the particles as being analyzed using Zetasizer. The obtained capsaicin-loaded NLCs were then characterized by entrapment efficiency (EE) and loading capacity (LC). The release characteristics followed Higuchi kinetics, and the prolonged capsaicin release may result in the reduction in skin irritation. These results could demonstrate the potentials of capsaicinloaded lipid-based nanoparticles for topical drug delivery.

Keywords: capsaicin, lipid-based nanoparticles, nanostructured lipid carriers, topical drug delivery system

Procedia PDF Downloads 76

Authors: Melkamu Tadesse Getachew

Abstract:

Intelligent control systems have revolutionized biomedical engineering, advancing research and enhancing medical practice. This review paper examines the impact of intelligent control on various aspects of biomedical engineering. It analyzes how these systems enhance precision and accuracy in biomedical instrumentation, improving diagnostics, monitoring, and treatment. Integration challenges are addressed, and potential solutions are proposed. The paper also investigates the optimization of drug delivery systems through intelligent control. It explores how intelligent systems contribute to precise dosing, targeted drug release, and personalized medicine. Challenges related to controlled drug release and patient variability are discussed, along with potential avenues for overcoming them. The comparison of algorithms used in intelligent control systems in biomedical control is also reviewed. The implications of intelligent control in computational and systems biology are explored, showcasing how these systems enable enhanced analysis and prediction of complex biological processes. Challenges such as interpretability, human-machine interaction, and machine reliability are examined, along with potential solutions. Intelligent control in biomedical engineering also plays a crucial role in risk management during surgical operations. This section demonstrates how intelligent systems improve patient safety and surgical outcomes when integrated into surgical robots, augmented reality, and preoperative planning. The challenges associated with these implementations and potential solutions are discussed in detail. In summary, this review paper comprehensively explores the widespread impact of intelligent control on biomedical engineering, showing the future of human health issues promising. It discusses application areas, challenges, and potential solutions, highlighting the transformative potential of these systems in advancing research and improving medical practice.

Keywords: Intelligent control systems, biomedical instrumentation, drug delivery systems, robotic surgical instruments, Computational monitoring and modeling

Procedia PDF Downloads 44

Authors: Sarika Gupta, Harshika Khanna, Ajay K Verma, Surya Kant

Abstract:

Background: Drug-resistant tuberculosis (DR-TB) is a growing health challenge to global TB control efforts. Pediatric DR-TB is one of the neglected infectious diseases. In our previously published report, we have notified an increased prevalence of DR-TB in the pediatric population at a tertiary health care centre in North India which was estimated as 17.4%, 15.1%, 18.4%, and 20.3% in (%) in the year 2018, 2019, 2020, and 2021. Limited evidence exists about a pattern of drug resistance, side effect profile and programmatic outcomes of Paediatric DR-TB treatment. Therefore, this study was done to find out the pattern of resistance, side effect profile and treatment outcome. Methodology: This was a prospective cohort study conducted at the nodal drug-resistant tuberculosis centre of a tertiary care hospital in North India from January 2021 to December 2022. Subjects included children aged between 0-18 years of age with a diagnosis of DR-TB, on the basis of GeneXpert (rifampicin [RIF] resistance detected), line probe assay and drug sensitivity testing (DST) of M. tuberculosis (MTB) grown on a culture of body fluids. Children were classified as monoresistant TB, polyresistant TB (resistance to more than 1 first-line anti-TB drug, other than both INH and RIF), MDR-TB, pre-XDR-TB and XDR-TB, as per the WHO classification. All the patients were prescribed DR TB treatment as per the standard guidelines, either shorter oral DR-TB regimen or a longer all-oral MDR/XDR-TB regimen (age below five years needed modification). All the patients were followed up for side effects of treatment once per month. The patient outcomes were categorized as good outcomes if they had completed treatment and cured or were improving during the course of treatment, while bad outcomes included death or not improving during the course of treatment. Results: Of the 50 pediatric patients included in the study, 34 were females (66.7%) and 16 were male (31.4%). Around 33 patients (64.7%) were suffering from pulmonary TB, while 17 (33.3%) were suffering from extrapulmonary TB. The proportions of monoresistant TB, polyresistant TB, MDR-TB, pre-XDR-TB and XDR-TB were 2.0%, 0%, 50.0%, 30.0% and 18.0%, respectively. Good outcome was reported in 40 patients (80.0%). The 10 bad outcomes were 7 deaths (14%) and 3 (6.0%) children who were not improving. Adverse events (single or multiple) were reported in all the patients, most of which were mild in nature. The most common adverse events were metallic taste 16(31.4%), rash and allergic reaction 15(29.4%), nausea and vomiting 13(26.0%), arthralgia 11 (21.6%) and alopecia 11 (21.6%). Serious adverse event of QTc prolongation was reported in 4 cases (7.8%), but neither arrhythmias nor symptomatic cardiac side effects occurred. Vestibular toxicity was reported in 2(3.9%), and psychotic symptoms in 4(7.8%). Hepatotoxicity, hypothyroidism, peripheral neuropathy, gynaecomastia, and amenorrhea were reported in 2 (4.0%), 4 (7.8%), 2 (3.9%), 1(2.0%), and 2 (3.9%) respectively. None of the drugs needed to be withdrawn due to uncontrolled adverse events. Conclusion: Paediatric DR TB treatment achieved favorable outcomes in a large proportion of children. DR TB treatment regimen drugs were overall well tolerated in this cohort.

Keywords: pediatric, drug-resistant, tuberculosis, adverse events, treatment

Procedia PDF Downloads 66

Authors: Zh. Saffari, A. Naeimi, M. S. Ekrami-Kakhki, F. Hamidi

Abstract:

Fe3O4 is one of the important magnetic oxides with spinel structure; it has exhibited unique electric and magnetic properties based on the electron transfer between Fe2+ and Fe3+ in the octahedral sites. Fe3O4 has received considerable attention in various areas such as cancer therapy, drug targeting, enzyme immobilization catalysis, magnetic cell separation, magnetic refrigeration systems and super-paramagnetic materials Fe3O4–TiO2 nanostructures were synthesized by simple, effective and new co-precipitation method assisted by ultrasonic reaction at room temperatures with organic surfactant. The effect of various parameters such as temperature, time, and power on the size and morphology of the product was investigated. Alternating gradient force magnetometer shows that Fe3O4 nanoparticles exhibit super-paramagnetic behaviour at room temperature. For preparation of nanocomposite, 1 g of TiO2 nanostructures were dispersed in 100 mL of ethanol. 0.25 g of Fe(NO3)2 and 2 mL of octanoic acid was added to the solution as a surfactant. Then, NaOH solution (1.5 M) was slowly added into the solution until the pH of the mixture was 7–8. After complete precipitation, the solution placed under the ultrasonic irradiation for 30 min. The product was centrifuged, washed with distilled water and dried in an oven at 100 °C for 3 h. The resulting red powder was calcinated at 800 °C for 3 h to remove any organic residue. The photocatalytic behaviour of Fe3O4–TiO2 nanoparticles was evaluated using the degradation of a Methyl Violet (MV) aqueous solution under ultraviolet light irradiation. As time increased, more and more MV was adsorbed on the nanoparticles catalyst, until the absorption peak vanish. The MV concentration decreased rapidly with increasing UV-irradiation time

Keywords: magnetic, methyl violet, nanocomposite, photocatalytic

Procedia PDF Downloads 255

Authors: Garzon V., Bustos R., Salvador J. P., Marco M. P., Pinacho D. G.

Abstract:

Bacterial resistance to antimicrobial treatment has increased significantly in recent years, making it a public health problem. Large numbers of bacteria are resistant to all or nearly all known antimicrobials, creating the need for the development of new types of antimicrobials or the use of “last line” antimicrobial drug therapies for the treatment of multi-resistant bacteria. Some of the chemical groups of antimicrobials most used for the treatment of infections caused by multiresistant bacteria in the clinic are Glycopeptide (Vancomycin), Polymyxin (Colistin), Lipopeptide (Daptomycin) and Carbapenem (Meropenem). Molecules that require therapeutic drug monitoring (TDM). Due to the above, a methodology based on nanobiotechnology based on an optical and electrochemical biosensor is being developed, which allows the evaluation of the plasmatic levels of some antimicrobials such as glycopeptide, polymyxin, lipopeptide and carbapenem quickly, at a low cost, with a high specificity and sensitivity and that can be implemented in the future in public and private health hospitals. For this, the project was divided into five steps i) Design of specific anti-drug antibodies, produced in rabbits for each of the types of antimicrobials, evaluating the results by means of an immunoassay analysis (ELISA); ii) quantification by means of an electrochemical biosensor that allows quantification with high sensitivity and selectivity of the reference antimicrobials; iii) Comparison of antimicrobial quantification with an optical type biosensor; iv) Validation of the methodologies used with biosensor by means of an immunoassay. Finding as a result that it is possible to quantify antibiotics by means of the optical and electrochemical biosensor at concentrations on average of 1,000ng/mL, the antibodies being sensitive and specific for each of the antibiotic molecules, results that were compared with immunoassays and HPLC chromatography. Thus, contributing to the safe use of these drugs commonly used in clinical practice and new antimicrobial drugs.

Keywords: antibiotics, electrochemical biosensor, optical biosensor, therapeutic drug monitoring

Procedia PDF Downloads 82

Authors: Akwu N. A., Naidoo Y., Salau V. F., Olofinsan K. A.

Abstract:

Grewia lasiocarpa E. Mey. ex Harv. (Malvaceae) is a Southern African medicinal plant indigenously used with other plants for birthing problems. The anti-diabetic properties of the hexane, chloroform, and methanol extracts of Grewia lasiocarpa stem bark were assessed using in vitro α-glucosidase enzyme inhibition assay. The predictive in silico drug-likeness and toxicity properties of the phytocompounds were conducted using the pKCSM, ADMElab, and SwissADME computer-aided online tools. The highest α-glucosidase percentage inhibition was observed in the hexane extract (86.76%, IC50= 0.24 mg/mL), followed by chloroform (63.08%, IC50= 4.87 mg/mL) and methanol (53.22%, IC50= 9.41 mg/mL); while acarbose, the standard anti-diabetic drug was (84.54%, IC50= 1.96 mg/mL). The α-glucosidase assay revealed that the hexane extract exhibited the strongest carbohydrate inhibiting capacity and is a better inhibitor than the standard reference drug-acarbose. The computational studies also affirm the results observed in the in vitroα-glucosidaseassay. Thus, the extracts of G. lasiocarpa may be considered a potential plant-sourced compound for treating type 2 diabetes mellitus. This is the first study on the anti-diabetic properties of Grewia lasiocarpa hexane, chloroform, and methanol extracts using in vitro and in silico models.

Keywords: grewia lasiocarpa, α-glucosidase inhibition, anti-diabetes, ADMET

Procedia PDF Downloads 104

Authors: Ilaria Manca, Ilaria Manca, Francesca Pettinau, Ignazia Mocci, Elisabetta M. Usai, Barbara Pittau

Abstract:

Lamotrigine is a phenyltriazine used in the treatment of epilepsy and bipolar disorder type I. The purpose of this study was to test and compare various solid forms of immediate release (IR) lamotrigine products, at different strenghts, in order to study their disaggregation and dissolution behavior. IR products are designed to release their active substance promptly after administration. Concentration of hydrochloric acid in gastric juice is about 0.1-0.001 M, so FDA (Food and Drug Administration) recommends, for lamotrigine regular tablets, dissolution tests in HCl 0.1 M.Toinvestigate the pH dependency of drug release in the entire gastrointestinal tract, we worked at two additional media with different pH values (4.5 and 6.8), that reflect conditions in it. To afford acceptable dissolution rates, tablets must disintegrate. Disaggregation of constituent particles increases the surface area and substantially increases the dissolution rate. For this reason availability of an active substance from tablets depends on its ability to disintegrate fast in dissolution media. pH of gastrointestinal fluid affects drug absorption by conditioning its solubility and dissolution, but also tablet disintegration may be influenced by it. To obtain information about the quantitative relationship between different mixture components, Nuclear Magnetic Resonance (NMR) spectroscopy was used. We also investigate tablet hardness. The investigation carried out confirms pH 1.2 as the ideal environment for the immediate availability of the active substance.

Keywords: dissolution, disaggregation, Lamotrigine, bioequivalence

Procedia PDF Downloads 453

Authors: Hari Bezwada, Michelle Cheon, Ryan Divan, Hannah Escritor, Michelle Kagramian, Isha Korgaonkar, Maya MacAdams, Udgita Pamidigantam, Richard Pilny, Eleanor Race, Angadh Singh, Nathan Zhang, LeeAnn Nguyen, Fina Liotta

Abstract:

Malaria is a deadly disease caused by the Plasmodium parasite, which continues to develop resistance to current antimalarial drugs. In this research project, the effectiveness of numerous thiazole derivatives was explored in inhibiting the PfPKG, a crucial part of the Plasmodium life cycle. This study involved the synthesis of six thiazole-derived amides to inhibit the PfPKG pathway. Nuclear Magnetic Resonance (NMR) spectroscopy and Infrared (IR) spectroscopy were used to characterize these compounds. Furthermore, AutoDocking software was used to predict binding affinities of these thiazole-derived amides in silico. In silico, compound 6 exhibited the highest predicted binding affinity to PfPKG, while compound 5 had the lowest affinity. Compounds 1-4 displayed varying degrees of predicted binding affinity. In-vitro, it was found that compound 4 had the best percent inhibition, while compound 5 had the worst percent inhibition. Overall, all six compounds had weak inhibition (approximately 30-39% at 10 μM), but these results provide a foundation for future drug discovery experiments.

Keywords: Medicinal Chemistry, Malaria, drug discovery, PfPKG, Thiazole, Plasmodium

Procedia PDF Downloads 98

Authors: Malahat Rezaee, Mahiran Basri, Raja Noor Zaliha Raja Abdul Rahman, Abu Bakar Salleh

Abstract:

Sodium diclofenac is one of the most commonly used drugs of nonsteroidal anti-inflammatory drugs (NSAIDs). It is especially effective in the controlling the severe conditions of inflammation and pain, musculoskeletal disorders, arthritis, and dysmenorrhea. Formulation as nanoemulsions is one of the nanoscience approaches that have been progressively considered in pharmaceutical science for transdermal delivery of drug. Nanoemulsions are a type of emulsion with particle sizes ranging from 20 nm to 200 nm. An emulsion is formed by the dispersion of one liquid, usually the oil phase in another immiscible liquid, water phase that is stabilized using surfactant. Palm kernel oil esters (PKOEs), in comparison to other oils; contain higher amounts of shorter chain esters, which suitable to be applied in micro and nanoemulsion systems as a carrier for actives, with excellent wetting behavior without the oily feeling. This research was aimed to study the effect of O/S ratio on stability and rheological behavior of sodium diclofenac loaded and unloaded palm kernel oil esters nanoemulsion systems. The effect of different O/S ratio of 0.25, 0.50, 0.75, 1.00 and 1.25 on stability of the drug-loaded and unloaded nanoemulsion formulations was evaluated by centrifugation, freeze-thaw cycle and storage stability tests. Lecithin and cremophor EL were used as surfactant. The stability of the prepared nanoemulsion formulations was assessed based on the change in zeta potential and droplet size as a function of time. Instability mechanisms including coalescence and Ostwald ripening for the nanoemulsion system were discussed. In comparison between drug-loaded and unloaded nanoemulsion formulations, drug-loaded formulations represented smaller particle size and higher stability. In addition, the O/S ratio of 0.5 was found to be the best ratio of oil and surfactant for production of a nanoemulsion with the highest stability. The effect of O/S ratio on rheological properties of drug-loaded and unloaded nanoemulsion systems was studied by plotting the flow curves of shear stress (τ) and viscosity (η) as a function of shear rate (γ). The data were fitted to the Power Law model. The results showed that all nanoemulsion formulations exhibited non-Newtonian flow behaviour by displaying shear thinning behaviour. Viscosity and yield stress were also evaluated. The nanoemulsion formulation with the O/S ratio of 0.5 represented higher viscosity and K values. In addition, the sodium diclofenac loaded formulations had more viscosity and higher yield stress than drug-unloaded formulations.

Keywords: nanoemulsions, palm kernel oil esters, sodium diclofenac, rheoligy, stability

Procedia PDF Downloads 423

Authors: A. V. Shrirao, N. I. Kochar, A. V. Chandewar

Abstract:

The flower extract of Butea monosperma herb has been used traditionally in India for medicinal purposes. The plant has been reported to treat hyperglycemia and associated hyperlipidemia. Hyperlipidemia and oxidative stress are known to accelerate coronary artery disease and progression of atherosclerotic lesions. The present work was undertaken to investigate the possible antihyperlipidemic and antioxidative effect of Butea monosperma flowers on hyperlipidemic rats. Hyperlipidemia was induced in rats by a single intraperitonial (i.p.) injection of Triton WR 1339 (400 mg/kg) and it showed sustained elevated levels of serum cholesterol and triglyceride. Ethanolic extract of Butea monosperma flowers (Et-BM) (250 and 500 mg/kg/day) was administered to normal and hyperlipidemic rats for 14 days. Serum and liver tissue were analyzed at three different time intervals for lipid profile and antioxidants enzymes and the activity were compared to the cholesterol-lowering drug, Atorvastatin (10 mg/kg). Parameters were altered during hyperlipidemia and reverted back to near normal values after Et-BM treatment or standard drug Atorvastatin. Lipid peroxidation decreased whereas the activities of superoxide dismutase, glutathione peroxidase and catalase increased in Et-BM treated rats. Pronounced changes were observed at 500 mg/kg of Et-BM for 2 weeks and it was comparable to the standard drug Atorvastatin. The current study provides strong evidence that Et-BM has a remarkable beneficial effect in treating hyperlipidemia and ROS without any side effects at the dosage and duration studied.

Keywords: antioxidant, butea monopserma, hyperlipidemia, triton WR 1339

Procedia PDF Downloads 318

Authors: Geetakshi Arora, Danish Malhotra

Abstract:

Diabetic wounds are serious health issues and often fail to heal, leading to limb amputation that makes the life of the patient miserable. Delayed wound healing has been characterized by an increase in matrix metalloproteinase-9 (MMP-9). Thus research throughout the world has been going on to develop selective MMP-9 inhibitors for aiding diabetic wound healing. Bioactive constituents from natural sources always served as potential leads in drug development with high rates of success. Considering the need for novel selective MMP-9 inhibitors and the importance of natural bioactive compounds in drug development, we have screened a library of bioactive constituents from plant sources that were effective in diabetic wound healing on human MMP-9 (hMMP-9) using molecular docking studies. Screened constituents are ranked according to their dock score, ∆G value (binding affinity), and Ligand efficiency evaluated from FleXX docking and Hyde scoring modules available with drug designing platform LeadIT. Rhamnocitrin showed the highest correlation between dock score, ∆G value (binding affinity), and Ligand efficiency was further explored for binding interactions with hMMP-9. The overall study suggest that Rhamnocitrin is sufficiently decorated with both hydrophilic and hydrophobic substitutions that perfectly block hMMP-9 and act as a potential lead in the design and development of selective hMMP-9 inhibitors.

Keywords: MMP-9, diabetic wound, molecular docking, phytoconstituents

Procedia PDF Downloads 126

Authors: Nihar Ranjan, Derrick Watkins, Dev P. Arya

Abstract:

Current methods in the study of antibiotic activity of ribosome targeted antibiotics are dependent on cell based bacterial inhibition assays or various forms of ribosomal binding assays. These assays are typically independent of each other and little direct correlation between the ribosomal binding and bacterial inhibition is established with the complementary assay. We have developed novel high-throughput capable assays for ribosome targeted drug discovery. One such assay examines the compounds ability to bind to a model ribosomal RNA A-site. We have also coupled this assay to other functional orthogonal assays. Such analysis can provide valuable understanding of the relationships between two complementary drug screening methods and could be used as standard analysis to correlate the affinity of a compound for its target and the effect the compound has on a cell.

Keywords: bacterial resistance, aminoglycosides, screening, drugs

Procedia PDF Downloads 370

Authors: Berredjem Hajira, Benlaifa Meriem, Becheker Imene, Bardi Rafika, Djebar Med Reda

Abstract:

Recent acquired or reactivation T.gondii infection is a serious complication in HIV patients. Classical serological diagnosis relies on the detection of anti-Toxoplasma immunoglobulin ; however, serology may be unreliable in HIV immunodeficient patients who fail to produce significant titers of specific antibodies. PCR assays allow a rapid diagnosis of Toxoplasma infection. In this study, we compared the value of the PCR for diagnosing active toxoplasmosis in cerebrospinal fluid and blood samples from HIV patients. Anti-Toxoplasma antibodies IgG and IgM titers were determined by ELISA. In parallel, nested PCR targeting B1 gene and conventional PCR-ELISA targeting P30 gene were used to detect T. gondii DNA in 25 blood samples and 12 cerebrospinal fluid samples from patients in whom toxoplasmic encephalitis was confirmed by clinical investigations. A total of 15 negative controls were used. Serology did not contribute to confirm toxoplasmic infection, as IgG and IgM titers decreased early. Only 8 out 25 blood samples and 5 out 12 cerebrospinal fluid samples PCRs yielded a positive result. 5 patients with confirmed toxoplasmosis had positive PCR results in either blood or cerebrospinal fluid samples. However, conventional nested B1 PCR gave best results than the P30 gene one for the detection of T.gondii DNA in both samples. All samples from control patients were negative. This study demonstrates the unusefulness of the serological tests and the high sensitivity and specificity of PCR in the diagnosis of toxoplasmic encephalitis in HIV patients.

Keywords: cerebrospinal fluid, HIV, Toxoplasmosis, PCR

Procedia PDF Downloads 377

Authors: Paris Binos

Abstract:

The present work investigates developmental aspects of the duration of isolated vowels in infants with normal hearing compared to those who received cochlear implants (CIs) before two years of age. Infants with normal hearing produced shorter vowel duration since this find related with more mature production abilities. First isolated vowels are transparent during the protophonic stage as evidence of an increased motor and linguistic control. Vowel duration is a crucial factor for the transition of prelexical speech to normal adult speech. Despite current knowledge of data for infants with normal hearing more research is needed to unravel productions skills in early implanted children. Thus, isolated vowel productions by two congenitally hearing-impaired Greek infants (implantation ages 1:4-1:11; post-implant ages 0:6-1:3) were recorded and sampled for six months after implantation with a Nucleus-24. The results compared with the productions of three normal hearing infants (chronological ages 0:8-1:1). Vegetative data and vocalizations masked by external noise or sounds were excluded. Participants had no other disabilities and had unknown deafness etiology. Prior to implantation the infants had an average unaided hearing loss of 95-110 dB HL while the post-implantation PTA decreased to 10-38 dB HL. The current research offers a methodology for the processing of the prelinguistic productions based on a combination of acoustical and auditory analyses. Based on the current methodological framework, duration measured through spectrograms based on wideband analysis, from the voicing onset to the end of the vowel. The end marked by two co-occurring events: 1) The onset of aperiodicity with a rapid change in amplitude in the waveform and 2) a loss in formant’s energy. Cut-off levels of significance were set at 0.05 for all tests. Bonferroni post hoc tests indicated that difference was significant between the mean duration of vowels of infants wearing CIs and their normal hearing peers. Thus, the mean vowel duration of CIs measured longer compared to the normal hearing peers (0.000). The current longitudinal findings contribute to the existing data for the performance of children wearing CIs at a very young age and enrich also the data of the Greek language. The above described weakness for CI’s performance is a challenge for future work in speech processing and CI’s processing strategies.

Keywords: cochlear implant, duration, spectrogram, vowel

Procedia PDF Downloads 261

Authors: Matej Buzgo, Erico Himawan, Ksenija JašIna, Aiva Simaite

Abstract:

Electrospinning is a versatile and efficient technology for producing nanofibers for biomedical applications. One of the most common polymers used for the preparation of nanofibers for regenerative medicine and drug delivery applications is polycaprolactone (PCL). PCL is a biocompatible and bioabsorbable material that can be used to stimulate the regeneration of various tissues. It is also a common material used for the development of drug delivery systems by blending the polymer with small active molecules. However, for many drug delivery applications, e.g. cancer immunotherapy, PCL biodegradation rate that may exceed 9 months is too long, and faster nanofiber dissolution is needed. In this paper, we investigate the dissolution and small molecule release rates of PCL blends with two hydrophilic polymers: polyethylene oxide (PEO) or polyvinylpyrrolidone (PVP). We show that adding hydrophilic polymer to the PCL reduces the water contact angle, increases the dissolution rate, and strengthens the interactions between the hydrophilic drug and polymer matrix that further sustain its release. Finally using this method, we were also able to increase the nanofiber degradation rate when PCL-PEO and PCL-PVP were used as a shell in the electrospun core-shell nanofibers and spread up the release of active proteins from their core. Electrospinning can be used for the preparation of the core-shell nanofibers, where active ingredients are encapsulated in the core and their release rate is regulated by the shell. However, such fibers are usually prepared by coaxial electrospinning that is an extremely low-throughput technique. An alternative is emulsion electrospinning that could be upscaled using needleless blades. In this work, we investigate the possibility of using emulsion electrospinning for encapsulation and sustained release of the growth factors for the development of the organotypic skin models. The core-shell nanofibers were prepared using the optimized formulation and the release rate of proteins from the fibers was investigated for 2 weeks – typical cell culture conditions.

Keywords: electrospinning, polycaprolactone (PCL), polyethylene oxide (PEO), polyvinylpyrrolidone (PVP)

Procedia PDF Downloads 273

Authors: R. M. Noah, N. M. Nasir, M. R. Jais, M. S. S. Wahab, M. H. Abdullah, A. S. S. Raj

Abstract:

Infectious diseases are getting more difficult to treat due to the resistant strains of bacteria. Current generations of antibiotics are most likely ineffective against multi-drug resistant strains bacteria. Thus, there is an urgent need in search of natural antibiotics in particular from medicinal plants. One of the common medicinal plants, Melaleuca cajuputi, has been reported to possess antibacterial properties. The study was conducted to evaluate and justify the presence of antibacterial activity of Melaleuca cajuputi essential oil (EO) against the multi-drug resistant bacteria. Clinical isolates obtained from the teaching hospital were re-assessed to confirm the exact identity of the bacteria to be tested, namely methicillin-resistant staphylococcus aureus (MRSA), carbapenem-resistant enterobacteriaceae (CRE), and extended-spectrum beta-lactamases producer (ESBLs). A well diffusion method was done to observe the inhibition zones of the essential oil against the bacteria. Minimum inhibitory concentration (MIC) was determined using the microdilution method in 96-well flat microplate. The absorbance was measured using a microplate reader. Minimum bactericidal concentration (MBC) was performed using the agar medium method. The zones of inhibition produced by the EO against MRSA, CRE, and ESBL were comparable to that of generic antibiotics used, gentamicin and augmentin. The MIC and MBC results highlighted the antimicrobial efficacy of the EO. The outcome of this study indicated that the EO of Melaleuca cajuputi had antibacterial activity on the multi-drug resistant bacteria. This finding was eventually substantiated by electron microscopy work.

Keywords: melaleuca cajuputi, antibacterial, resistant bacteria, essential oil

Procedia PDF Downloads 122

Authors: Alena O. Stepanova, Vera S. Chernonosova, Tatyana S. Godovikova, Konstantin A. Bulatov, Andrey Y. Patrushev, Pavel P. Laktionov

Abstract:

Trauma and arthrosis, not to mention cartilage destruction in overweight and elders put hyaline cartilage lesion among the most frequent diseases of locomotor system. These problems combined with low regeneration potential of the cartilage make regeneration of articular cartilage a high-priority task of tissue engineering. Many types of matrices, the procedures of their installation and autologous chondrocyte implantation protocols were offered, but certain aspects including adhesion of the implant with surrounding cartilage/bone, prevention of the ossification and fibrosis were not resolved. Simplification and acceleration of the procedures resulting in restoration of normal cartilage are also required. We have demonstrated that human chondroblasts can be successfully cultivated at the surface of electrospun scaffolds and produce extracellular matrix components in contrast to chondroblasts grown in homogeneous hydrogels. To restore cartilage we offer to use stacks of electrospun scaffolds fixed with photopolymerized solution of prepared from gelatin and chondroitin-4-sulfate both modified by glycidyl methacrylate and non-toxic photoinitator Darocur 2959. Scaffolds were prepared from nylon 6, polylactide-co-glicolide and their mixtures with modified gelatin. Illumination of chondroblasts in photopolymerized solution using 365 nm LED light had no effect on cell viability at compressive strength of the gel less than0,12 MPa. Stacks of electrospun scaffolds provide good compressive strength and have the potential for substitution with cartilage when biodegradable scaffolds are used. Vascularization can be prevented by introduction of biostable scaffolds in the layers contacting the subchondral bone. Studies of two-component materials (2-3 sheets of electrospun scaffold) implanted in the knee-joints of rabbits and fixed by photopolymerization demonstrated good crush resistance, biocompatibility and good adhesion of the implant with surrounding cartilage. Histological examination of the implants 3 month after implantation demonstrates absence of any inflammation and signs of replacement of the biodegradable scaffolds with normal cartilage. The possibility of intraoperative population of the implants with autologous cells is being investigated.

Keywords: chondroblasts, electrospun scaffolds, hyaline cartilage, photopolymerized gel

Procedia PDF Downloads 284

Authors: Smruti Mahapatra, Dipankar Biswas, Richard Um, Michael Meggyesy, Riccardo Serra, Noah Gorelick, Steven Marra, Amir Manbachi, Mark G. Luciano

Abstract:

Intracranial pressure (ICP) is profoundly regulated by the effects of cardiac pulsation and the volume of the incoming blood. Furthermore, these effects on ICP are incremented by the presence of a rigid skull that does not allow for changes in total volume during the cardiac cycle. These factors play a pivotal role in cerebrospinal fluid (CSF) dynamics and distribution, with consequences that are not well understood to this date and that may have a deep effect on the Central Nervous System (CNS) functioning. We designed this study with two specific aims: (a) To study how pulsatility influences local CSF flow, and (b) To study how modulating intracranial pressure affects drug distribution throughout the SAS globally. In order to achieve these aims, we built an elaborate in-vitro model of the SAS closely mimicking the dimensions and flow rates of physiological systems. To modulate intracranial pressure, we used an intracranially implanted, cardiac-gated, volume-oscillating balloon (CADENCE device). Commercially available dye was used to visualize changes in CSF flow. We first implemented two control cases, seeing how the tracer behaves in the presence of pulsations from the brain phantom and the balloon individually. After establishing the controls, we tested 2 cases, having the brain and the balloon pulsate together in sync and out of sync. We then analyzed the distribution area using image processing software. The in-sync case produced a significant increase, 5x times, in the tracer distribution area relative to the out-of-sync case. Assuming that the tracer fluid would mimic blood flow movement, a drug introduced in the SAS with such a system in place would enhance drug distribution and increase the bioavailability of therapeutic drugs to a wider spectrum of brain tissue.

Keywords: blood-brain barrier, cardiac-gated, cerebrospinal fluid, drug delivery, neurosurgery

Procedia PDF Downloads 183

Authors: Peter Yamoah, Frasia Oosthuizen

Abstract:

Introduction: Reporting of Adverse Events Following Immunization continues to be a challenge. Pharmacovigilance centers throughout the world are mandated by the WHO to submit AEFI reports from various countries to a large pool of adverse drug reaction electronic database called Vigibase. Despite the relevant information of AEFI in Vigibase, it is unavailable to the general public. However, the WHO has an alternative website called VigiAccess which is an open access website serving as a repository of reported adverse drug reactions and AEFIs. The aim of the study was to ascertain the reporting pattern of a number of commonly used vaccines in VigiAccess. Methods: VigiAccess was thoroughly searched on the 5th of February 2018 for AEFI reports of measles vaccine, oral polio vaccine (OPV), yellow fever vaccine, pneumococcal vaccine, rotavirus vaccine, meningococcal vaccine, tetanus vaccine and tuberculosis (BCG) vaccine. These were reports from all pharmacovigilance centers in the world from the time they joined the WHO drug monitoring program. Results: After a thorough search in VigiAccess, there were 9,062 measles vaccine AEFIs, 185,829 OPV AEFIs, 24,577 yellow fever vaccine AEFIs, 317,208 pneumococcal vaccine AEFIs, 73,513 rotavirus vaccine AEFIs, 145,447 meningococcal vaccine AEFIs, 22,781 tetanus vaccine AEFIs and 35,556 BCG vaccine AEFIs. Conclusion: The study revealed that out of the eight vaccines studied, pneumococcal vaccines are associated with the highest number of AEFIs whilst measles vaccines were associated with the least AEFIs.

Keywords: vaccines, adverse reactions, VigiAccess, adverse event reporting

Procedia PDF Downloads 155

Authors: Noora Al Muftah, Reda Rawi, Richard Thompson, Halima Bensmail

Abstract:

Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers of response to targeted agents. There is an urgent need to identify biomarkers that predict which patients with are most likely to respond to treatment. Systematic efforts to correlate tumor mutational data with biologic dependencies may facilitate the translation of somatic mutation catalogs into meaningful biomarkers for patient stratification. To identify genomic features associated with drug sensitivity and uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we have screened and integrated a panel of several hundred cancer cell lines from different databases, mutation, DNA copy number, and gene expression data for hundreds of cell lines with their responses to targeted and cytotoxic therapies with drugs under clinical and preclinical investigation. We found mutated cancer genes were associated with cellular response to most currently available Glioma cancer drugs and some frequently mutated genes were associated with sensitivity to a broad range of therapeutic agents. By linking drug activity to the functional complexity of cancer genomes, systematic pharmacogenomic profiling in cancer cell lines provides a powerful biomarker discovery platform to guide rational cancer therapeutic strategies.

Keywords: cancer, gene network, Lasso, penalized regression, P-values, unbiased estimator

Procedia PDF Downloads 409

Authors: Natalie Riley, Anita Quigley, Robert M. I. Kapsa, George W. Greene

Abstract:

As the fields of medicine and bionics grow rapidly in technological advancement, the future and success of it depends on the ability to effectively interface between the artificial and the biological worlds. The biggest obstacle when it comes to implantable, electronic medical devices, is maintaining a ‘clean’, low noise electrical connection that allows for efficient sharing of electrical information between the artificial and biological systems. Implant fouling occurs with the adhesion and accumulation of proteins and various cell types as a result of the immune response to protect itself from the foreign object, essentially forming an electrical insulation barrier that often leads to implant failure over time. Lubricin (LUB) functions as a major boundary lubricant in articular joints, a unique glycoprotein with impressive anti-adhesive properties that self-assembles to virtually any substrate to form a highly ordered, ‘telechelic’ polymer brush. LUB does not passivate electroactive surfaces which makes it ideal, along with its innate biocompatibility, as a coating for implantable bionic electrodes. It is the aim of the study to investigate LUB’s anti-fouling properties and its potential as a safe, bioinspired material for coating applications to enhance the performance and longevity of implantable medical devices as well as reducing the frequency of implant replacement surgeries. Native, bovine-derived LUB (N-LUB) and recombinant LUB (R-LUB) were applied to gold-coated mylar surfaces. Fibroblast, chondrocyte and neural cell types were cultured and grown on the coatings under both passive and electrically stimulated conditions to test the stability and anti-adhesive property of the LUB coating in the presence of an electric field. Lactate dehydrogenase (LDH) assays were conducted as a directly proportional cell population count on each surface along with immunofluorescent microscopy to visualize cells. One-way analysis of variance (ANOVA) with post-hoc Tukey’s test was used to test for statistical significance. Under both passive and electrically stimulated conditions, LUB significantly reduced cell attachment compared to bare gold. Comparing the two coating types, R-LUB reduced cell attachment significantly compared to its native counterpart. Immunofluorescent micrographs visually confirmed LUB’s antiadhesive property, R-LUB consistently demonstrating significantly less attached cells for both fibroblasts and chondrocytes. Preliminary results investigating neural cells have so far demonstrated that R-LUB has little effect on reducing neural cell attachment; the study is ongoing. Recombinant LUB coatings demonstrated impressive anti-adhesive properties, reducing cell attachment in fibroblasts and chondrocytes. These findings and the availability of recombinant LUB brings into question the results of previous experiments conducted using native-derived LUB, its potential not adequately represented nor realized due to unknown factors and impurities that warrant further study. R-LUB is stable and maintains its anti-fouling property under electrical stimulation, making it suitable for electroactive surfaces.

Keywords: anti-fouling, bioinspired, cell attachment, lubricin

Procedia PDF Downloads 124

Authors: Rajesh S. Mony, Vaidyaratnam Oushadhasala

Abstract:

An attempt is made in this study to evolve a drug development modality based on classical Ayurvedic knowledge base as well as on modern scientific methodology. The present study involves (a) identification of a specific ailment condition, (b) the selection of a polyherbal formulation, (c) deciding suitable extraction procedure, (d) confirming the efficacy of the combination by in-vitro trials and (e) fixing up the recommended dose. The ailment segment selected is arthritic condition. The selected herbal combination is Kunturushka, Vibhitaki, Guggulu, Haridra, Maricha and Nirgundi. They were selected as per Classical Ayurvedic references, Authentified as per API (Ayurvedic Pharmacopeia of India), Extraction of each drug was done by different ratios of Hydroalcoholic menstrums, Invitro assessment of each extract after removing residual solvent for anti-Inflammatory, anti-arthritic activities (by UV-Vis. Spectrophotometer with positive control), Invitro assessment of each extract for COX enzyme inhibition (by UV-Vis. Spectrophotometer with positive control), Selection of the extracts was made having good in-vitro activity, Performed the QC testing of each selected extract including HPTLC, that is the in process QC specifications, h. Decision of the single dose with mixtures of selected extracts was made as per the level of in-vitro activity and available toxicology data, Quantification of major groups like Phenolics, Flavonoids, Alkaloids and Bitters was done with both standard Spectrophotometric and Gravimetric methods, Method for Marker assay was developed and validated by HPTLC and a good resolved HPTLC finger print was developed for the single dosage API (Active Pharmaceutical Ingredient mixture of extracts), Three batches was prepared to fix the in process and API (Active Pharmaceutical Ingredient) QC specifications.

Keywords: drug development, antiinflammatory, quality stardardisation, planar chromatography

Procedia PDF Downloads 99